ObjectiveTo investigate the effects of Shenxiong Huanglian Jiedu decoction on the clearance of amyloid β-protein （Aβ） and neuronal damage in the mouse model of Alzheimer's disease （AD）. MethodsA total of 36 SPF-grade 2-month-old C57BL/6J mice were used in this study， and the modeling was performed by bilateral hippocampal injection of Aβ oligomers in C57BL/6J mice. The experiment was conducted with a blank group， a sham operation group， a model group， low- and high-dose （3.27，6.54 g·kg^-1， respectively） Shenxiong Huanglian Jiedu decoction groups， and a positive control （donepezil hydrochloride， 0.65 mg·kg^-1） group. At the end of the drug intervention， the learning and memory abilities and the activities of mice were evaluated by the Morris water maze and open field tests. Brain histopathology was examined by hematoxylin-eosin and Nissl staining. Additionally， in vivo imaging was employed to measure the metabolism of fluorescent Aβ in the cerebrospinal fluid， and staining of ionized calcium-binding adapter molecule-1 （Iba-1） was employed to assess microglial activation in the hippocampal tissue. Additionally， neurotrophin-3 （NT-3） and brain-derived neurotrophic factor （BDNF） levels in the brain tissue and serum were determined by the immunofluorescence assay and enzyme-linked immunosorbent assay. Western blot was conducted to determine the expression of inflammation and pathway-related proteins in the hippocampal tissue. ResultsCompared with the blank group and the sham operation group， the escape latency of the mice in the model group was prolonged， the platform residence time was shortened， the hippocampal tissue showed pathological manifestations such as neuronal pyknosis， Nissl body dissolution， and microglia activation. The metabolic rate of fluorescent Aβ through cerebrospinal fluid was slowed down， and the expression levels of BDNF， NT-3， and interleukin-10 （IL-10） in the hippocampus were significantly decreased （P<0.01）. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88） and phosphorylated nuclear transcription factor-κB （p-NF-κB p65） in hippocampus were significantly increased （P<0.05， P<0.01）. Compared with the model group， the escape latency of mice in the low and high dose groups of Chinese medicine and donepezil group was shortened， and the platform residence time was prolonged. Neuronal karyopyknosis， Nissl body dissolution and microglia activation in hippocampus were improved. Fluorescence Aβ was metabolized faster by cerebrospinal fluid. The expression of BDNF and NT-3 in hippocampus was increased （P<0.01）， and the expression of TLR4， MyD88 and p-NF-κB p65 was significantly decreased （P<0.05， P<0.01）. The expression of TNF-α in the hippocampus of the high-dose group was significantly decreased （P<0.05）， and the expression of IL-10 was significantly increased （P<0.05）. The expression of TNF-α， IL-6 and IL-1β in the hippocampus of the donepezil group was significantly decreased （P<0.05， P<0.01）. ConclusionShenxiong Huanglian Jiedu decoction may mitigate neuronal damage and enhance cerebrospinal fluid flow in the mouse model of AD， thereby promoting the clearance of Aβ and improving the learning and memory abilities. These beneficial effects are likely mediated through the inhibition of microglial activation， reduction of inflammation， and modulation of the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the effects of Shenxiong Huanglian Jiedu decoction on the clearance of amyloid β-protein （Aβ） and neuronal damage in the mouse model of Alzheimer's disease （AD）. MethodsA total of 36 SPF-grade 2-month-old C57BL/6J mice were used in this study， and the modeling was performed by bilateral hippocampal injection of Aβ oligomers in C57BL/6J mice. The experiment was conducted with a blank group， a sham operation group， a model group， low- and high-dose （3.27，6.54 g·kg^-1， respectively） Shenxiong Huanglian Jiedu decoction groups， and a positive control （donepezil hydrochloride， 0.65 mg·kg^-1） group. At the end of the drug intervention， the learning and memory abilities and the activities of mice were evaluated by the Morris water maze and open field tests. Brain histopathology was examined by hematoxylin-eosin and Nissl staining. Additionally， in vivo imaging was employed to measure the metabolism of fluorescent Aβ in the cerebrospinal fluid， and staining of ionized calcium-binding adapter molecule-1 （Iba-1） was employed to assess microglial activation in the hippocampal tissue. Additionally， neurotrophin-3 （NT-3） and brain-derived neurotrophic factor （BDNF） levels in the brain tissue and serum were determined by the immunofluorescence assay and enzyme-linked immunosorbent assay. Western blot was conducted to determine the expression of inflammation and pathway-related proteins in the hippocampal tissue. ResultsCompared with the blank group and the sham operation group， the escape latency of the mice in the model group was prolonged， the platform residence time was shortened， the hippocampal tissue showed pathological manifestations such as neuronal pyknosis， Nissl body dissolution， and microglia activation. The metabolic rate of fluorescent Aβ through cerebrospinal fluid was slowed down， and the expression levels of BDNF， NT-3， and interleukin-10 （IL-10） in the hippocampus were significantly decreased （P<0.01）. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88） and phosphorylated nuclear transcription factor-κB （p-NF-κB p65） in hippocampus were significantly increased （P<0.05， P<0.01）. Compared with the model group， the escape latency of mice in the low and high dose groups of Chinese medicine and donepezil group was shortened， and the platform residence time was prolonged. Neuronal karyopyknosis， Nissl body dissolution and microglia activation in hippocampus were improved. Fluorescence Aβ was metabolized faster by cerebrospinal fluid. The expression of BDNF and NT-3 in hippocampus was increased （P<0.01）， and the expression of TLR4， MyD88 and p-NF-κB p65 was significantly decreased （P<0.05， P<0.01）. The expression of TNF-α in the hippocampus of the high-dose group was significantly decreased （P<0.05）， and the expression of IL-10 was significantly increased （P<0.05）. The expression of TNF-α， IL-6 and IL-1β in the hippocampus of the donepezil group was significantly decreased （P<0.05， P<0.01）. ConclusionShenxiong Huanglian Jiedu decoction may mitigate neuronal damage and enhance cerebrospinal fluid flow in the mouse model of AD， thereby promoting the clearance of Aβ and improving the learning and memory abilities. These beneficial effects are likely mediated through the inhibition of microglial activation， reduction of inflammation， and modulation of the TLR4/MyD88/NF-κB signaling pathway.

OBJECTIVE: To explore the effect of chitosan (CS) hydrogel loaded with tendon-derived stem cells (TDSCs; hereinafter referred to as TDSCs/CS hydrogel) on tendon-to-bone healing after rotator cuff repair in rabbits. METHODS: TDSCs were isolated from the rotator cuff tissue of 3 adult New Zealand white rabbits by Henderson step-by-step enzymatic digestion method and identified by multidirectional differentiation and flow cytometry. The 3rd generation TDSCs were encapsulated in CS to construct TDSCs/CS hydrogel. The cell counting kit 8 (CCK-8) assay was used to detect the proliferation of TDSCs in the hydrogel after 1-5 days of culture in vitro, and cell compatibility of TDSCs/CS hydrogel was evaluated by using TDSCs alone as control. Another 36 adult New Zealand white rabbits were randomly divided into 3 groups ( n=12): rotator cuff repair group (control group), rotator cuff repair+CS hydrogel injection group (CS group), and rotator cuff repair+TDSCs/CS hydrogel injection group (TDSCs/CS group). After establishing the rotator cuff repair models, the corresponding hydrogel was injected into the tendon-to-bone interface in the CS group and TDSCs/CS group, and no other treatment was performed in the control group. The general condition of the animals was observed after operation. At 4 and 8 weeks, real-time quantitative PCR (qPCR) was used to detect the relative expressions of tendon forming related genes (tenomodulin, scleraxis), chondrogenesis related genes (aggrecan, sex determining region Y-related high mobility group-box gene 9), and osteogenesis related genes (alkaline phosphatase, Runt-related transcription factor 2) at the tendon-to-bone interface. At 8 weeks, HE and Masson staining were used to observe the histological changes, and the biomechanical test was used to evaluate the ultimate load and the failure site of the repaired rotator cuff to evaluate the tendon-to-bone healing and biomechanical properties. RESULTS: CCK-8 assay showed that the CS hydrogel could promote the proliferation of TDSCs ( P<0.05). qPCR results showed that the expressions of tendon-to-bone interface related genes were significantly higher in the TDSCs/CS group than in the CS group and control group at 4 and 8 weeks after operation ( P<0.05). Moreover, the expressions of tendon-to-bone interface related genes at 8 weeks after operation were significantly higher than those at 4 weeks after operation in the TDSCs/CS group ( P<0.05). Histological staining showed the clear cartilage tissue and dense and orderly collagen formation at the tendon-to-bone interface in the TDSCs/CS group. The results of semi-quantitative analysis showed that compared with the control group, the number of cells, the proportion of collagen fiber orientation, and the histological score in the TDSCs/CS group increased, the vascularity decreased, showing significant differences ( P<0.05); compared with the CS group, the proportion of collagen fiber orientation and the histological score in the TDSCs/CS group significantly increased ( P<0.05), while there was no significant difference in the number of cells and vascularity ( P>0.05). All samples in biomechanical testing failed at the repair site during the testing process. The ultimate load of the TDSCs/CS group was significantly higher than that of the control group ( P<0.05), but there was no significant difference compared to the CS group ( P>0.05). CONCLUSION TDSCs/CS hydrogel can induce cartilage regeneration to promote rotator cuff tendon-to-bone healing.
Rabbits ; Animals ; Rotator Cuff/surgery* ; Chitosan ; Hydrogels ; Rotator Cuff Injuries/surgery* ; Wound Healing ; Tendons/surgery* ; Collagen ; Stem Cells ; Biomechanical Phenomena

Objective:To investigate the efficacy of robot-assisted femoral tunnel localization in reconstruction of the medial patellofemoral ligament (MPFL).Methods:A retrospective study was conducted to analyze the 36 patients who had been admitted to Department of Sports Medicine, The Fourth Hospital of Wuhan between January 2019 and January 2022 due to recurrent patellar dislocation. There were 15 males and 21 females; age: 23.5 (18.3, 29.0) years; number of dislocations: 2.5 (2.0, 3.0). They were stratified into 2 cohorts based on utilization of robot-assistance. In the observation group (17 cases), the femoral tunnel localization was robot-assisted in MPFL reconstruction; in the control group (19 cases), the femoral tunnel localization was guided by C-arm fluoroscopy in MPFL reconstruction. The 2 groups were compared in terms of operation time, frequency of guide wire placement, visual analogue scale (VAS) at postoperative 1 d, patellar tilt angle (PTA) and the disparity between actual femoral tunnel insertion and ideal tunnel insertion point (Sch?ttle point) at postoperative 1 to 3 d, and Lysholm knee score and International Knee Documentation Committee (IKDC) score at the last follow-up.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for 12.0 (10.3, 13.0) months. In the observation group, the operation time [(64.1±16.7) min], frequency of guide wire placement [1.0 (1.0, 2.0) times], VAS [2.5 (2.0, 3.0) points], and disparity between actual femoral tunnel insertion and ideal tunnel insertion point [(4.7±1.2) mm] were significantly better than those in the control group [(84.2±19.7) min, 3.0 (2.0, 4.0) times, 3.5 (3.0, 4.0) points, and (6.1±1.2) mm] ( P<0.05). There was no statistical difference between the 2 groups in PTA, Lysholm knee score or IKDC score ( P>0.05). Conclusions:The short-term clinical efficacy of robot-assisted femoral tunnel localization is satisfactory in MPFL reconstruction. Compared with the intraoperative C-arm fluoroscopy, robot-assisted localization can decrease the frequency of guide wire placement, enhance femoral tunnel accuracy and efficiency, and alleviate more postoperative pain for the patients.

Objective　To investigate the epidemiology and genomic characterizations of carbapenem-resistant Escherichia coli (CREC) from a tertiary hospital in Guangzhou, Guangdong province, China from January 2021 to December 2023. Methods　The non-repetitive CREC isolates identified at the hospital from January 2021 to December 2023 were included and their clinical characteristics were analyzed through the clinical record system. A total of 42 CREC isolates were randomly selected for species identification, antimicrobial susceptibility testing, and multilocus sequence typing. Whole-genome sequencing and bioinformatics analysis were conducted to investigate the antimicrobial resistance genes, virulence-related genes, replicons, and plasmid types carrying the carbapenem resistance genes in CREC. Results　A total of 2 887 Escherichia coli (EC) isolates were collected from the hospital between January 2021 to December 2023, including 105 CREC strains. The prevalence rates of CREC over the three years were 1.76%, 2.80%, and 5.69%, respectively, showing a significant upward trend (P<0.001). All 42 CREC isolates showed resistance to multiple antibiotics, with resistance rates for amoxicillin-clavulanate, ceftazidime, and cefepime all at 100.00%, ertapenem and imipenem at 97.62%, levofloxacin at 83.33%, and amikacin at 45.24%. All CREC isolates were susceptible to tigecycline. The 42 CREC strains were classified into 14 ST types, with the main types being ST167 (28.57%), ST410 (26.19%), and ST131 (9.52%). ST410 CREC isolates carried significantly more fim, algA, icsP/sopA, and high-pathogenicity island (HPI) related virulence genes than ST167 isolates (P<0.05), whereas aslA and hcp-2 were significantly lower than ST167 (P<0.05). The carbapenem resistance genes carried by CREC were primarily blaNDM-5 (n=34), followed by blaNDM-1 (n=6), with only one isolate carrying blaKPC-2. These carbapenem resistance genes were mainly located on IncF (n=27) and IncX3 (n=11) type of plasmids. Conclusions　The prevalence of CREC significantly increased from 2021 to 2023 in this hospital, with ST167 and ST410 as the dominant types. ST410 CREC is a newly prevalent high-risk clone carrying adhesion, biofilm formation, and HPI-related virulence genes, and there is an urgent need to monitor its epidemiological status and transmission characteristics to provide a basis for the formulation of control measures.

Objective:To investigate the early clinical effect of fascia lata autograft bridging combined with the long head of biceps tendon transposition for treatment of irreparable massive rotator cuff tear.Methods:All of 31 cases of massive irreparable rotator cuff tear treated in our hospital from March 2016 to March 2020 were analyzed retrospectively. Among them, 17 cases (10 males, 7 females) were repaired with fascia lata autograft bridging under arthroscopy (patch group), the average age was 61.47±6.63 (ranging from 51 to 72) and 14 cases (4 males, 10 females) were repaired with fascia lata autograft bridging combined with the long head of biceps tendon transposition (combined group), the average age was 62.57±6.11 (ranging from 53 to 71). The operation time, intraoperative blood loss, postoperative complications, visual analogue scale (VAS) of pain before operation, at 1 week and 12 months after operation, Constant-Murley score of shoulder joint and American Association of shoulder and elbow Surgeons (ASES) score before operation, at 6 months and 12 months after operation were compared between the two groups. The outcome of rotator cuff healing was evaluated by MRI 1 year after operation.Results:All patients were followed up for 12-27 months (mean 18.33 ±6.8 months). There was no perioperative complication, and there was no significant difference in operation time between the two groups ( P>0.05) . The VAS score in the patch group was significantly higher than the combined group 1 week after operation ( t=2.09, P=0.048) , and there was no significant difference in VAS score 12 months after operation between the two groups. Constant-Murley score and ASES score in the combined group were significantly higher than the patch group at 6 months after operation ( t=5.23, P<0.001; t=4.45, P<0.001) , and there was no significant difference in Constant score and ASES score between the two groups at 12 months after operation. Constant score and ASES score in the two groups were significantly higher than those before operation. One year after operation, the MRI of the affected shoulder showed that the incidence of autograft patch thinning (Sugaya grade III) was 52.94%, the autograft patch structure failure rate (Sugaya grade IV and V) was 17.65% in the patch group, the autograft patch thinning rate (Sugaya grade III) was 35.71%, and the structural failure rate (Sugaya grade IV and V) was 7.14% in the combined group. The difference was statistically significant (χ 2=7.12, P=0.028) . Conclusion:Fascia lata autograft patch bridging combined with long head of biceps tendon transposition technique for treatment of irreparable massive rotator cuff tear has less pain 1 week after operation and better recovery of shoulder function half a year after operation. MRI showed better patch healing 1 year after operation.

【Objective】 To explore the effects of insulin on the QT interval and induced arrhythmias of cardiomyocytes derived from human induced pluripotent stem cells （hiPSC-CMs）. 【Methods】 Immunofluorescence staining and flow cytometry were used to analyze the purity of hiPSC-CMs. Microelectrode array （MEA） was utilized to detect the electrophysiological changes including heart rate （HR）， field potential duration （FPD， which is similar to QT interval in ECG）， FPDc （FPD corrected by HR）， conduction velocity （CV）， and spike amplitude before and after insulin treatment. The effects of E4031 on QT interval prolongation and induced arrhythmias of hiPSC-CMs were evaluated before and after treatment with insulin. 【Results】 hiPSC-CMs highly expressed myocardial specific marker cTnT. The purity of hiPSC-CMs was 97.1%. After 5-day insulin treatment of hiPSC-CMs， HR increased by （11.9±3.3）%， FPD shortened by （22.7±2.8）%， FPDc shortened by （15.6±1.6）%， and spike amplitude increased by （39.1±7.9）% when compared with untreated group， but CV remained unchanged. 10 nmol/L of E4031 could prolong the FPDc of hiPSC-CMs by （37.8±9.0）%， and 30 nmol/L of E4031 could induce arrhythmias. After insulin treatment， 10 nmol/L of E4031 prolonged the FPDc of hiPSC-CMs by （21.8±3.1）% （compared with the untreated group， insulin decreased FPDc prolongation by E4031， 37.8%±9.0% vs. 21.8%±3.1%， P<0.05）， while 30 nmol/L of E4031 did not induce arrhythmias. 【Conclusion】 Insulin can shorten the QT interval of hiPSC-CMs and significantly reduce the QT interval prolongation and the risk of arrhythmias induced by drugs.

Objective:To explore the feasibility, safety and effectiveness of anatomical partial lobectomy.Methods:The clinical data of 3 336 patients with lung nodules underwent anatomical partial lobectomy in our center from November 2013 to November 2019 were retrospectively analyzed. We set the safety margin distance according to the imaging feature of the lesion. The surgeons then anatomically detached the major vessels and bronchus in this region, resected the targeted lung tissue along the plane, and completed the resection of anatomical pulmonary lobe and clean and sampling of systemic lymph nodules.Results:A total of 668 cases were multiple nodules and 2 668 cases were solitary pulmonary nodules. According to the postoperative pathological results, 283 cases were benign, 1 197 cases were preinvasive lesions (including 38 cases of atypical adenomatous hyperplasia, 445 cases of adenocarcinoma in situ and 714 cases of minimally invasive adenocarcinoma), 1 713 cases were invasive adenocarcinoma, 73 cases were non-adenocarcinoma and 70 cases were metastatic carcinoma. Among 1 786 invasive primary lung cancers, 11 cases received preoperative neoadjuvant chemotherapy, and their postoperative pathologic diagnoses were stage ypIA. Other 1 775 cases who did not receive postoperative neoadjuvant treatment included 1 587 cases in stage ⅠA, 112 cases in stage ⅠB, 3 cases in stage ⅡA, 18 cases in stage ⅡB, 37 cases in stage ⅢA, 9 cases in stage ⅢB, 9 cases in stage Ⅳ. The average operation time was (127.3±55.3) minutes, and the mean postoperative hospital stay was (4.8±2.4) days. The incidence rate of complications (grade>2) was 1.1%(38/3 336), and no death occurred during 30 days after operation.Conclusion:Anatomic partial lobectomy has good clinical applicability, safety and effectiveness, which is worthy of clinical application and recommendation.

Objective:To explore the feasibility, safety and effectiveness of anatomical partial lobectomy.Methods:The clinical data of 3 336 patients with lung nodules underwent anatomical partial lobectomy in our center from November 2013 to November 2019 were retrospectively analyzed. We set the safety margin distance according to the imaging feature of the lesion. The surgeons then anatomically detached the major vessels and bronchus in this region, resected the targeted lung tissue along the plane, and completed the resection of anatomical pulmonary lobe and clean and sampling of systemic lymph nodules.Results:A total of 668 cases were multiple nodules and 2 668 cases were solitary pulmonary nodules. According to the postoperative pathological results, 283 cases were benign, 1 197 cases were preinvasive lesions (including 38 cases of atypical adenomatous hyperplasia, 445 cases of adenocarcinoma in situ and 714 cases of minimally invasive adenocarcinoma), 1 713 cases were invasive adenocarcinoma, 73 cases were non-adenocarcinoma and 70 cases were metastatic carcinoma. Among 1 786 invasive primary lung cancers, 11 cases received preoperative neoadjuvant chemotherapy, and their postoperative pathologic diagnoses were stage ypIA. Other 1 775 cases who did not receive postoperative neoadjuvant treatment included 1 587 cases in stage ⅠA, 112 cases in stage ⅠB, 3 cases in stage ⅡA, 18 cases in stage ⅡB, 37 cases in stage ⅢA, 9 cases in stage ⅢB, 9 cases in stage Ⅳ. The average operation time was (127.3±55.3) minutes, and the mean postoperative hospital stay was (4.8±2.4) days. The incidence rate of complications (grade>2) was 1.1%(38/3 336), and no death occurred during 30 days after operation.Conclusion:Anatomic partial lobectomy has good clinical applicability, safety and effectiveness, which is worthy of clinical application and recommendation.

Objective:To investigate the clinical efficacy of fixed-bearing unicompartmental knee arthroplasty (UKA) in the treatment of anteromedial knee osteoarthritis or spontaneous osteonecrosis of the femoral condyle.Methods:Between June 2017 and June 2018, 62 consecutive patients were treated at Department of Joint Surgery, Fuzhou Second Hospital Affiliated to Xiamen University for anteromedial knee osteoarthritis or spontaneous osteonecrosis of the femoral condyle using a fixed-bearing UKA system. They were 27 men and 35 women, aged from 58 to 85 years (average, 69.8 years). There were 58 cases of anteromedial knee osteoarthritis and 4 cases of spontaneous osteonecrosis of the femoral condyle. The courses of disease ranged from 2 to 10 years (average, 5.1 years). Medial unicompartmental knee arthroplasty was performed for all the patients on the fixation platform SLED. Recorded were the hip-knee-ankle angle (HKA) of the patients 2 days after operation, Oxford knee score (OKS) and American Knee Society score (KSS) at the final follow-up and post-operative complications.Results:The 62 patients were followed up for 9 to 21 months (average, 15.6 months). Tibial plateau fracture occurred in one case who eventually obtained bony union after open reduction and internal fixation. Another case had a wound healing problem which responded to drainage and debridement with prosthesis preservation. Another case presented prepatellar pain which was improved after physical therapy. In the 62 patients, the HKA 2 days after operation (172.27°±1.61°) was significantly improved compared to the preoperative value (177.79°±1.32°), the OKS at the final follow-up (19.8±2.7) significantly lower than the preoperative value (50.2±3.1), and the KSS at the final follow-up (89.7±2.6) significantly higher than the preoperative value (49.6±5.2) (all P<0.05). Follow-ups revealed no cases of joint infection or prosthetic loosening. Conclusion:Fixed-bearing unicompartmental knee arthroplasty can lead to fine short-term outcomes for anteromedial knee osteoarthritis or spontaneous osteonecrosis of the femoral condyle.