1.Treadmill training activates endogenous neural stem cells to promote spinal cord injury repair in mice
Chanjuan CHEN ; Zeyu SHANGGUAN ; Qizhe LI ; Wei TAN ; Qing LI
Chinese Journal of Tissue Engineering Research 2025;29(19):3976-3982
BACKGROUND:Treadmill training is one of the effective ways to promote the recovery of motor function after spinal cord injury.Treadmill training can promote neurogenesis,but the effect of different intensities of treadmill training on the activation of endogenous stem cells is still unclear. OBJECTIVE:To analyze the activation effect of different intensities of treadmill training on endogenous neural stem cells in the spinal cord of mice after spinal cord injury. METHODS:Fifty female C57BL/6J mice were divided into control group,spinal cord injury group,low-,moderate-,and high-intensity exercise groups with 10 mice in each group by random number table method.T10 segment spinal cord injury model was constructed by the clamp method in spinal cord injury group,low-,moderate-,and high-intensity exercise groups.On day 7 after spinal cord injury,mice in the low-,moderate-,and high-intensity exercise groups were respectively trained on the treadmill with corresponding intensity,3 times/d,10 min/times,6 times a week for 28 consecutive days.At 3,7,14,21,and 28 days after treadmill training,the hind limb motor function was evaluated by BMS score.At 28 days after treadmill training,the spinal cord tissue of the injured area was obtained,and the expression of epidermal growth factor receptor,glial fibrillary acidic protein,and 5-Ethynyl-2'-deoxyuridine(EdU),a proliferative marker,was detected.Hematoxylin-eosin staining was used to observe the morphology of spinal cord. RESULTS AND CONCLUSION:(1)The BMS score of mice in the spinal cord injury group was lower than that in the control group(P<0.05).With the extension of treadmill training time,the BMS scores of mice with spinal cord injury gradually increased,and the BMS scores of mice in moderate-intensity exercise group on days 14 and 21 after treadmill training were higher than those in spinal cord injury group and low-and high-intensity exercise groups(P<0.05).The BMS score of mice in moderate-and high-intensity exercise group was higher than that in spinal cord injury group and low-intensity exercise group at 28 days after treadmill training(P<0.05).(2)Compared with the control group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in low-,moderate-,and high-intensity exercise groups(P<0.05),and the highest was found in moderate-intensity exercise group.Compared with control group,the proportion of glial fibrillary acidic protein positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of glial fibrillary acidic protein positive cells was lower in low-,moderate-,and high-intensity exercise groups(P<0.05),and the moderate-intensity exercise group was the lowest.(3)Hematoxylin-eosin staining showed that a large cavity was formed in the injured area of mice with spinal cord injury,and the cavity in the injured area of mice with spinal cord injury decreased after different intensities of treadmill training,and the decrease was most obvious in the moderate-intensity exercise group.(4)These results indicate that low-,moderate-,and high-intensity treadmill training can promote the recovery of motor function of mice with spinal cord injury by activating endogenous neural stem cells,and the effect of moderate-intensity exercise training is the most obvious.
2.A multicenter clinical study on intramedullary vancomycin injection for preventing periprosthetic joint infection in total knee arthroplasty
Te LIU ; Jun FU ; Shiguang LAI ; Zhuo ZHANG ; Chi XU ; Lei GENG ; Yang LUO ; Peng REN ; Xin ZHI ; Quanbo JI ; Heng ZHANG ; Runkai ZHAO ; Haichao REN ; Ye TAO ; Qingyuan ZHENG ; Zeyu FENG ; Jianfeng YANG ; Yiming WANG ; Pengcheng LI ; Shuai LIU ; Wei CHAI ; Xiang LI ; Huiwu LI ; Xiaogang ZHANG ; Baochao JI ; Xianzhe LIU ; Xinzhan MAO ; Jianbing MA ; Xiangxiang SUN ; Jiying CHEN ; Yonggang ZHOU ; Jinliang WANG ; Weijun WANG ; Guoqiang ZHANG ; Ming NI
Chinese Journal of Orthopaedics 2025;45(12):803-811
Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.
3.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
4.A multicenter clinical study on intramedullary vancomycin injection for preventing periprosthetic joint infection in total knee arthroplasty
Te LIU ; Jun FU ; Shiguang LAI ; Zhuo ZHANG ; Chi XU ; Lei GENG ; Yang LUO ; Peng REN ; Xin ZHI ; Quanbo JI ; Heng ZHANG ; Runkai ZHAO ; Haichao REN ; Ye TAO ; Qingyuan ZHENG ; Zeyu FENG ; Jianfeng YANG ; Yiming WANG ; Pengcheng LI ; Shuai LIU ; Wei CHAI ; Xiang LI ; Huiwu LI ; Xiaogang ZHANG ; Baochao JI ; Xianzhe LIU ; Xinzhan MAO ; Jianbing MA ; Xiangxiang SUN ; Jiying CHEN ; Yonggang ZHOU ; Jinliang WANG ; Weijun WANG ; Guoqiang ZHANG ; Ming NI
Chinese Journal of Orthopaedics 2025;45(12):803-811
Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.
5.Isolation and culture of adult mouse cerebrospinal fluid-contacting neurons in vitro and characterization of self-renewal capacity
Zeyu SHANGGUAN ; Chanjuan CHEN ; Qizhe LI ; Wei TAN ; Haijian YAN ; Chunqing WANG ; Xiaowei DOU ; Qing LI
Chinese Journal of Tissue Engineering Research 2025;29(13):2728-2735
BACKGROUND:We have successfully isolated and cultured neonatal mouse cerebrospinal fluid-contacting neurons in vitro,but there is no study that reports an effective method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons.There is no study on whether the self-renewal ability of cerebrospinal fluid-contacting neurons changes with age.OBJECTIVE:To establish a method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons in vitro,and to characterize the self-renewal ability of adult mouse cerebrospinal fluid-contacting neurons and neonatal mouse cerebrospinal fluid-contacting neurons in vitro.METHODS:Primary cells containing cerebrospinal fluid-contacting neurons were isolated from the cervical medulla of adult mouse (3 months of age) in adherent culture and transfected with lentivirus fused with multimodal imaging genes.High-purity adult mouse cerebrospinal fluid-contacting neurons were obtained by puromycin screening in suspension culture in complete medium.The expression of neural stem cell markers Nestin and SOX2 was detected by immunofluorescence in adult mouse cerebrospinal fluid-contacting neurons,and the ability of adult mouse cerebrospinal fluid-contacting neurons to form spheres and pass on in vitro was observed.An equal number (5×103/mL) of passage 3 adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons were divided into two groups under the same conditions and inoculated into ultra-low adhesion plates containing complete medium in suspension culture at 5% CO2,37℃ thermostat,respectively.The self-renewal capacity of adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons was characterized by in vitro spheroid formation,CCK8 assay,qPCR,and western blot assay.RESULTS AND CONCLUSION:(1) High-purity cerebrospinal fluid-contacting neurons were successfully isolated from adult mouse,which expressed Nestin and SOX2 in vitro,and were able to form neurospheres and pass on continuously.(2) The in vitro self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse,and the neurospheres formed by day 4 of cell culture in neonatal mouse were about 150 μm in diameter,whereas the neurospheres formed by adult mouse tactile neurons were only 40 μm in diameter (P<0.0001).(3) CCK8 proliferation assay showed that the proliferative activity of adult mouse cerebrospinal fluid-contacting neurons was significantly weaker than that of neonatal mouse at all time points after culture (P<0.0001).(4) qPCR and western blot assay revealed that the mRNA (P<0.0001) and protein expression levels (P<0.01) of Nestin and SOX2 in cerebrospinal fluid-contacting neurons of adult mouse were significantly decreased compared with those of neonatal mouse.(5) The above results indicated that the self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse in vitro.
6.Isolation and culture of adult mouse cerebrospinal fluid-contacting neurons in vitro and characterization of self-renewal capacity
Zeyu SHANGGUAN ; Chanjuan CHEN ; Qizhe LI ; Wei TAN ; Haijian YAN ; Chunqing WANG ; Xiaowei DOU ; Qing LI
Chinese Journal of Tissue Engineering Research 2025;29(13):2728-2735
BACKGROUND:We have successfully isolated and cultured neonatal mouse cerebrospinal fluid-contacting neurons in vitro,but there is no study that reports an effective method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons.There is no study on whether the self-renewal ability of cerebrospinal fluid-contacting neurons changes with age.OBJECTIVE:To establish a method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons in vitro,and to characterize the self-renewal ability of adult mouse cerebrospinal fluid-contacting neurons and neonatal mouse cerebrospinal fluid-contacting neurons in vitro.METHODS:Primary cells containing cerebrospinal fluid-contacting neurons were isolated from the cervical medulla of adult mouse (3 months of age) in adherent culture and transfected with lentivirus fused with multimodal imaging genes.High-purity adult mouse cerebrospinal fluid-contacting neurons were obtained by puromycin screening in suspension culture in complete medium.The expression of neural stem cell markers Nestin and SOX2 was detected by immunofluorescence in adult mouse cerebrospinal fluid-contacting neurons,and the ability of adult mouse cerebrospinal fluid-contacting neurons to form spheres and pass on in vitro was observed.An equal number (5×103/mL) of passage 3 adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons were divided into two groups under the same conditions and inoculated into ultra-low adhesion plates containing complete medium in suspension culture at 5% CO2,37℃ thermostat,respectively.The self-renewal capacity of adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons was characterized by in vitro spheroid formation,CCK8 assay,qPCR,and western blot assay.RESULTS AND CONCLUSION:(1) High-purity cerebrospinal fluid-contacting neurons were successfully isolated from adult mouse,which expressed Nestin and SOX2 in vitro,and were able to form neurospheres and pass on continuously.(2) The in vitro self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse,and the neurospheres formed by day 4 of cell culture in neonatal mouse were about 150 μm in diameter,whereas the neurospheres formed by adult mouse tactile neurons were only 40 μm in diameter (P<0.0001).(3) CCK8 proliferation assay showed that the proliferative activity of adult mouse cerebrospinal fluid-contacting neurons was significantly weaker than that of neonatal mouse at all time points after culture (P<0.0001).(4) qPCR and western blot assay revealed that the mRNA (P<0.0001) and protein expression levels (P<0.01) of Nestin and SOX2 in cerebrospinal fluid-contacting neurons of adult mouse were significantly decreased compared with those of neonatal mouse.(5) The above results indicated that the self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse in vitro.
7.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
8.Observation on the effect of hydrogel probiotics colonized in inflammatory sites in the treatment of inflammatory bowel disease
Wei XU ; Meng LI ; Haoze WANG ; Kai CUI ; Zeyu XIAO
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(7):883-890
Objective·To construct a probiotic(Escherichia coli Nissle1917,EcN)system(EcN@PVA-ALG)loaded on polyvinyl alcohol(PVA)/alginate(ALG)hydrogel(PVA-ALG)rich in negative hydroxyl groups,and to explore its colonization in the inflammatory site of colon and its therapeutic effect on dextran sulfate sodium salt(DSS)-induced inflammatory bowel disease(IBD).Methods·EcN suspension was added to the PVA-ALG hydrogel,and then EcN@PVA-ALG hydrogel probiotic complex was obtained after screening and centrifugation.The synthesis of PVA-ALG hydrogel was verified by rheometer.The surface charge of EcN@PVA-ALG was detected by potentiometer and the load of EcN on PVA-ALG was observed by fluorescence microscope.The absorbance of EcN@PVA-ALG at 600 nm was detected by enzyme labeling instrument.Meanwhile,the bacterial plate count of EcN@PVA-ALG complex suspension was taken to study the growth activity of EcN in EcN@PVA-ALG.The CCK-8 kit was used to assess the inhibitory ability of EcN@PVA-ALG on HEK cell proliferation.In vivo imaging system(IVIS)was used to firstly analyze the enrichment of PVA-ALG on inflammatory colon to study its inflammatory targeting property;then EcN was loaded on PVA-ALG,and IVIS was used to observe the enrichment of EcN@PVA-ALG on inflammatory colon to study its ability to colonize the inflammatory site.To establish the model of IBD mice induced by DSS,EcN@PVA-ALG group(n=5)was given 1×108CFU EcN@PVA-ALG every day for 5 d,and PVA-ALG group,EcN group,PBS group and healthy control group with 5 mice were set up.During the treatment,the body mass of the mice was recorded every day.After treatment,the colonic tissue was taken,and the length of colon was measured.The disease activity index(DAI)score was graded.The levels of inflammatory cytokines,including tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-10 and transforming growth factor-β(TGF-β)were detected,and the pathological evaluation of colonic tissue was made by H-E staining.Results·Both PVA-ALG and EcN@PVA-ALG were negatively charged.EcN was successfully loaded onto PVA-ALG and PVA-ALG did not affect the growth viability of EcN,which contributed to the subsequent colonization of inflammatory colons.PVA-ALG had a favorable safety profile on normal cells.Compared with healthy controls,PVA-ALG had more than 2-fold enrichment effect on inflammatory colon tissue.In vitro and in vivo experiments revealed that EcN@PVA-ALG complex loaded with EcN had 8 times higher enrichment effect on inflammatory tissue than EcN without any modification.After EcN@PVA-ALG treatment,the body weight of mice recovered rapidly.The increase of DAI was significantly inhibited.The length of colon was similar to that of healthy mice.The levels of TNF-α and IL-6 decreased,while the levels of IL-10 and TGF-β increased.The crypt structure of colon tissue recovered.Conclusion·Compared to unmodified EcN,EcN@PVA-ALG promotes the colonization of EcN at inflammatory sites of colon and allows it to exert better efficacy on treating DSS-induced IBD.
9.Learning curve for a five-step procedure, transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction
Haiping ZENG ; Yonghui CHEN ; Lijie LUO ; Zijing ZHANG ; Zeyu LIN ; Yan CHEN ; Yaohui PENG ; Tao WANG ; Yansheng ZHENG ; Wenjun XIONG ; Wei WANG
Chinese Journal of Gastrointestinal Surgery 2024;27(9):938-944
Objective:To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ 2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M( Q1, Q3) and the Mann–Whitney U test was used for inter group comparison. Results:The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x 3-4.4757x 2+164.97x-264.4 ( P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor ( P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups ( P=0.238). Conclusion:Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.
10.Application of anterior esophageal wall full layer fixation and gastric tube guidance in total laparoscopic overlap method for intracorporeal esophagojejunostomy
Yan CHEN ; Xinrui YE ; Lijie LUO ; Zijing ZHANG ; Wenjun XIONG ; Haigang YANG ; Yaohui PENG ; Zeyu LIN ; Zhuoxuan ZHANG ; Wei WANG
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1074-1079
Objective:To explore the application of anterior esophageal wall full layer fixation and gastric tube guidance in total laparoscopic overlap method for intracorporeal esophagojejunostomy.Methods:Overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance is suitable for patients with advanced gastric cancer (clinical stage: cT1b~4aN0~3M0) and esophageal invasion <3 cm, who underwent radical total gastrectomy+ overlap esophagojejunostomy. The main operation procedure was performed as follows: A titanium clip was used for fixation of the full anterior wall of esophagus before overlap esophagojejunostomy, and the side‐to‐side esophagojejunostomy was performed with the linear stapler under the guidance of gastric tube. Then the titanium clip was removed after confirming that the correct cavity was entered. Finally, the common outlet was closed by two barbed sutures. A descriptive case series study was conducted. The clinical data of patients who underwent laparoscopic radical gastrectomy and overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance in Guangdong Provincial Hospital of Chinese medicine and the First Affiliated Hospital of Guangzhou University of Chinese medicine from May 2021 to June 2023 were retrospectively analyzed.Results:A total of 42 patients were collected, and all of them were successfully completed laparoscopic total radical gastrectomy without conversion to laparotomy or perioperative death. The esophagojejunostomy time, operative time, intraoperative blood loss was 17(5‐25) minutes, (258.8±38.0) minutes and 50(20‐200) ml, respectively. The incidence of esophageal false lumen was 0%, and there were no intraoperative complications. The time of gastric tube removal, initial fluid diet intake and the duration of postoperative hospital were 2(1‐5) , 4(1‐8) and 8(4‐21) days, respectively. There were no postoperative anastomotic hemorrhage, anastomotic stenosis and other related complications. One patient (2.38%) developed a Clavien‐Dindo IIIb complication, which was abdominal hemorrhage after operation. The second surgical exploration confirmed that the patient was bleeding due to gastroduodenal artery rupture. After intraoperative suture hemostasis, fluid expansion, blood transfusion and other treatments, the patient was discharged on the 15th day after the operation. Three patients (7.14%) developed Clavien‐Dindo grade II complications, including anastomotic leakage, chylous leakage and pulmonary infection, and were discharged after conservative treatment such as anti‐infection and prolonged retention of drainage tube.Conclusions:Laparoscopic overlap method for intracorporeal esophagojejunostomy with anterior esophageal wall fixation and gastric tube guidance can shorten the time of esophagojejunostomy and prevent the occurrence of false lumen, and do not increase anastomose‐related complications.

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