OBJECTIVE: To explore the methods, fixation points, and effectiveness of staged therapy using external fixation frame in treatment of infectious nonunion near knee joint. METHODS: A retrospective analysis was conducted on the clinical data of 60 patients with infectious nonunion near knee joint, who underwent staged therapy using external fixation frame between June 2021 and June 2024 and were followed up. There were 48 males and 12 females with an average age of 47.9 years (range, 16-70 years). The disease duration ranged from 9 months to 20 years, with a median of 14 months. Among them, 21 cases of infectious nonunion located in the distal femur, 36 cases in the proximal tibia, and 3 cases in the patella; 12 cases exhibited segmental bone defects (≥4 cm), while 48 cases presented with localized bone defects (<4 cm). Osteomyelitis was classified using the Cierny-Mader system, with 3 cases classified as type Ⅰ, 6 cases as type Ⅱ, 35 cases as type Ⅲ, and 16 cases as type Ⅳ. Preoperative C-reactive protein levels ranged from 15.1 to 55.8 mg/L (mean, 36.4 mg/L). The erythrocyte sedimentation rate was 35-80 mm/1 h (mean, 56.9 mm/1 h). The Hospital for Special Surgery (HSS) score for knee joint was 69.3±17.7 and the range of motion was (70.61±40.60)°. After debridement and placement of antibiotic carriers at the first-stage operation, unilateral orbital frames ( n=14), combined frames ( n=27), or Ilizarov frames ( n=19) were used for cross joint fixation ( n=9) or joint preservation fixation ( n=51). After 6-8 weeks of infection control, the bone grafting or bone transport was performed at the second-stage operation based on the type of bone defect, with internal fixation employed as an adjunct if necessary. After operation, the infection control and fracture healing were observed and the bone healing time was recorded. The knee joint function was assessed using the HSS score, and the knee joint range of motion was measured as well as the angle of motion loss. Patients were grouped according to the site of nonunion, type of external fixation frame, and fixation method. The bone healing time, change value of HSS score, and knee joint range of motion loss (difference between pre- and post-operation) were compared between groups. RESULTS: All infection markers returned to the normal range within 6 weeks after the first-stage operation. All patients were followed up 12-48 months (mean, 22.0 months) after the second-stage operation. There were 5 cases of needle tract infection during the external fixation period, and 3 cases of infection recurrence after the second-stage operation, all of which were cured after symptomatic treatment. The bone healing time was 6-18 months (mean, 11.0 months). At last follow-up, the HSS score was 88.5±7.9 and the range of motion was (61.84±40.59)°, with significant differences compared to preoperative values ( P<0.05); the knee joint range of motion loss was (8.77±11.07)°. The bone healing time was significantly longer in the distal femur group than in the proximal tibia group ( P<0.05), and in the unilateral orbital frames group than in the Ilizarov frames group and the combined frames group ( P<0.05). The angle of motion loss was significantly larger in the Ilizarov frames group than in the unilateral orbital frames group and the combined frames group ( P<0.05). The change value of HSS score was significantly higher in the cross joint fixation group than in the joint preservation fixation group ( P<0.05). CONCLUSION During the first-stage operation, debridement is performed and antibiotic carriers are placed to control infection. External fixation frames are then precisely positioned based on the distance between the lesion and the joint surface, avoiding the infected wound while ensuring mechanical balance. During the second-stage operation, bone grafting options are selected according to the extent of bone defects to enhance the bone union. Postoperative early functional exercises of the knee joint are permitted to improve joint function.
Humans ; Male ; Female ; Middle Aged ; Adult ; Fractures, Ununited/surgery* ; Retrospective Studies ; External Fixators ; Aged ; Knee Joint/surgery* ; Adolescent ; Young Adult ; Treatment Outcome ; Osteomyelitis/surgery* ; Fracture Fixation/instrumentation* ; Bone Transplantation ; Tibial Fractures/surgery*

OBJECTIVE: To explore the effectiveness of primary interventional revascularization combined with secondary perforator composite flap in the treatment of peripheral arterial disease (PAD) accompanied by soft tissue defects around the ankle. METHODS: Between January 2022 and January 2025, 12 patients with PAD and soft tissue defects around the ankle were admitted. Among them, there were 9 males and 3 females; their ages ranged from 52 to 82 years, with an average of 68.9 years. The causes of injury included 4 cases of traffic accident, 5 cases of falls, 1 case of falling from height, 1 case of foreign body puncture injury, and 1 case of electric shock injury. The infection duration ranged from 1 month to 35 years, with a median duration of 3.5 months. The wound size ranged from 5.5 cm×3.0 cm to 15.0 cm×9.0 cm. The ankle-brachial index (ABI) was 0.32±0.12. The visual analogue scale (VAS) score for pain was 3.3±0.5. Preoperative vascular stenosis assessment was performed in all patients, with primary intervention to dredge large and medium-sized arteries, followed by secondary repair of the wound using a perforator composite flap. The flap size ranged from 6.5 cm×4.0 cm to 16.0 cm×10.0 cm. The donor sites were sutured directly or repaired with skin grafts. After two stages of treatment, the effectiveness was evaluated by measuring ABI, observing flap survival and wound healing, assessing VAS scores, and American Orthopedic Foot and Ankle Society (AOFAS) scores. RESULTS: All 12 cases completed two stages of treatment; all patients were followed up after the second-stage treatment, with a follow-up period ranging from 7 to 28 months, with an average of 16.8 months. After the first-stage treatment, the skin temperature around the ankle was significantly higher than that before treatment, and the ABI increased to 0.71±0.07, with a significant difference ( t=9.918, P<0.001). After the second-stage treatment, the blisters on the distal end of the skin flap occurred in 3 cases. The flaps survived and the wounds healed, with a healing time ranging from 10 to 14 days (mean, 11.8 days). The incisions at the donor site healed by first intention, and the skin grafts survived. The VAS score was 0.5±0.5 at 3 weeks, which was significantly lower than that before treatment ( t=13.675, P<0.001). No infection recurrence occurred during follow-up. At 6 months after the second-stage treatment, the AOFAS score of the ankle joint ranged from 92 to 97, with an average of 94.7, all reaching excellent. CONCLUSION Interventional revascularization combined with perforator composite flap for staged treatment of PAD with ankle soft tissue defects can obtain good effectiveness, by unclogging the main blood vessels, improving lower limb blood supply, and improving the survival rate of the skin flap.
Humans ; Male ; Female ; Middle Aged ; Aged ; Peripheral Arterial Disease/surgery* ; Soft Tissue Injuries/surgery* ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Aged, 80 and over ; Ankle/blood supply* ; Treatment Outcome ; Ankle Brachial Index ; Skin Transplantation/methods*

Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

Objective To establish and validate a multimodal MRI radiomics model based on intratumoral and peritumoral heterogeneity for prediction of spatial pattern of locally recurrent high-grade gliomas(HGGs).Methods A retrospective analysis was conducted on the clinical and imaging data of all HGGs patients who underwent maximum safe resection followed by postoperative radiotherapy combined with temozolomide treatment and experienced in local recurrence in Army Medical Center of PLA from 2012 to 2021.Two radiologists independently assessed the spatial patterns of locally recurrence HGGs through continuous follow-up MRI data,and primarily categorized the pattern into intra-resection cavity recurrence and extra-resection cavity recurrence.The subjected patients were randomly divided into a training set and a validation set in a 7∶3 ratio.In the training set,Pearson or Spearman correlation analysis and least absolute shrinkage and selection operator(LASSO)analysis were employed to screen radiomic features within the intratumoral and peritumoral regions,as well as to calculate radiomic scores.A radiomics model was established using logistic regression analysis.The performance of the model was assessed using calibration curves,Hosmer-Lemeshow goodness-of-fit test,and the area under the receiver operating characteristic curve(AUC).Validation of the model was performed in the validation set.Results A total of 121 patients with locally recurrent HGGs were enrolled in this study,including 54 in intra-resection cavity recurrence group and 67 in extra-resection cavity recurrence group.Among them,84 were assigned into the training set and 37 into the validation set.In the training set,the radiomics score for the extra-resection cavity recurrence group was 0.424(0.278,0.573),which was higher than that for the intra-resection cavity recurrence group[-0.030(-0.226,0.248),P<0.001].In the validation set,the radiomics score for the extra-resection cavity recurrence group was 0.369(0.258,0.487),which was higher than that for the intra-resection cavity recurrence group[0.277(0.103,0.322),P=0.033].The established radiomics model exhibited good calibration and performed well in predicting spatial recurrence patterns,with an AUC value of 0.844(95%CI:0.749～0.914)in the training set and 0.706(95%CI:0.534～0.844)in the validation set.Conclusion Our multimodal radiomics model combined with intratumoral and peritumoral heterogeneity can predict the spatial pattern of locally recurrent HGGs,providing a basis for individualized treatment of HGGs.

Objective To observe the improvement effect and mechanism of emodin on lipopolysaccharide(LPS)-induced podocyte injury.Methods Human glomerular podocytes were used as the study object,and they were randomly divided into the blank control group,the LPS group,the emodin low-,medium-,and high-dose groups,and the emodin+lysophosphatidic acid[LP A,RhoA/RhoRho-associatedcoiled-coil kinase(ROCK)activator]group.Cell counting kit 8(CCK8)and 5-ethynyl-2'-deoxyuridine(EdU)staining were applied to detect the proliferation of glomerular podocytes,Transwell assay was used to test the migration of glomerular podocytes,flow cytometry was used to detect apoptosis of glomerular podocytes,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflammatory factors tumor necrosis factor α(TNF-α),interleukin(IL)-1β,and IL-18 in the supernatant of glomerular podocytes,and the protein expression levels of RhoA and ROCK in glomerular podocytes were determined by Western Blot.Results The optical density(OD)450nm,EdU positive cell rate and migration number of glomerular podocytes in the LPS group were lower than those in the blank control group,and the apoptosis rate,the levels of TNF-α,IL-1β and IL-18 in the supernatant,as well as the protein expression levels of RhoA and ROCK in the cells were higher than those in the blank control group,the differences being statistically significant(P＜0.05);the OD450nm,EdU positive cell rate and migration number of glomerular podocytes in the emodin low-,medium-,and high-dose groups were higher than those in the LPS group,while the apoptosis rate,levels of TNF-α,IL-1 β and IL-18 in supernatant,as well as RhoA and ROCK protein expression levels in cells were reduced compared with those in the LPS group,the differences being statistically significant(P＜0.05);the OD450nm and EdU positive cell rate and migration number of glomerular podocytes in LPA group were lower than those of emodin high-dose group,while the apoptosis rate,levels of TNF-α,IL-1 βand IL-18 in supernatant,as well as RhoA and ROCK protein expression levels in cells were higher than those of emodin high-dose group,the differences being all statistically significant(P＜0.05).Conclusion Emodin can improve LPS-induced podocyte injury,and its mechanism of action may be related to the inhibition of RhoA/ROCK signaling pathway.

ObjectiveTo understand the process and influencing factors affecting the utilization of influenza vaccination services and vaccination decision-making among the elderly in Shanghai, to explore the delivery of influenza vaccination services and the difficulties faced by the health service system, and to provide guidance for optimizing immunization strategies. MethodsBased on the vaccine hesitancy determinants matrix, semi-structured personal interviews were conducted with stakeholders involved in influenza vaccination services in Shanghai from January to February 2024, using a purposive sampling method. Participants were included until thematic saturation was achieved. Interview data were audio-recorded, transcribed, coded, and organized using NVivo 20 software, and analyzed using the thematic framework method. ResultsA total of 25 interviewees were included, including 9 medical staff, 12 elderly people aged 60 and above, and 4 family members. The study found that Shanghai had a well-managed and standardized influenza vaccination service. However, the promotion of vaccine-related information at the grassroots level was passive and limited. Out-of-pocket payment of the vaccine and cultural beliefs of the elderly negatively impacted vaccination rates. Meanwhile, recommendations from family, friends, and medical staff facilitated vaccination, although the impact varied depending on the type of medical staff. Neighborhood committees in townships and streets played a crucial role in delivering vaccination information to the target population. Additionally, the internet, social media, and the COVID-19 vaccine had both positive and negative impacts on influenza vaccination. Strategic optimization of vaccination should prioritize price concessions, enhance publicity strategies, and improve awareness, professionalism, and willingness among medical and healthcare workers to recommend vaccination. ConclusionThe influenza vaccination service in Shanghai is well-managed and standardized. However, it is essential to consider the influence of family and other support systems on the elderly. It is also necessary to enhance the professionalism, service awareness, and willingness to recommend among the medical staff. Furthermore, systematic interventions and publicity efforts should be effectively integrated with social media and the functions of neighborhood committees.

Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.

Objective To investigate the characteristics of blood routine,chest computed tomography(CT)imaging and short-term evolution of hemodialysis patients infected with Omicron variant of severe acute respiratory syndrom coronavirus 2(SARS-CoV-2).Methods A total of 204 patients diagnosed with Omicron variant infection in the First Hospital of Hohhot from September 2022 to September 2023 were retrospectively reviewed.Among them,89 patients with end-stage renal disease(ESRD)who were receiving hemodialysis were included in the hemo-dialysis group.The remaining 115 patients were control group,and the first blood routine results chest com-puted tomography(CT)imaging data were observed.Thirty-four patients in the hemodialysis group and 29 patients in the control group had complete pulmonary CT imaging data on the day of admission,5-6 days and 10-12 days after admission.The characteristics and chest CT scores of all cases were analyzed.Results 1)The percentage of monocytes,neutrophils,neutrophil/lymphocyte ratio and chest CT score of the hemo-dialysis group were higher than those of the control group,while the white blood cells,lymphocytes and lymphocyte percentage were lower than those of the control group.2)The positive rate of first chest CT was 49.4%in hemo-dialysis group and 35.7%in control group.3)The chest CT scores of the hemo-dialysis group and the control group on day 5 and day 6 were higher than those of first check.Chest CT was reexamined on days 10-12,and scores were higher in the hemo-dial-ysis group than in the control group.Conclusions Hemo-dialysis patients with COVID-19 have higher blood routine indexes,higher positive rate of lung CT and slower absorption than non-hemodialysis patients.

Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

BACKGROUND:Bushen Yiqi Huayu granule has the effect of replenishing qi and eliminating blood stasis,tonifying kidney and smoothing collages,and is often used in the treatment of osteoporosis.At present,there are few studies on the effect of Bushen Yiqi Huayu granule on the callus angiogenesis of osteoporotic fractures. OBJECTIVE:To explore the mechanism of Bushen Yiqi Huayu granule by up-regulating extracellular signal-regulated kinase/mitogen-activated protein kinases(ERK/MAPK)signaling pathway to improve callus angiogenesis after fracturing in osteoporotic rats. METHODS:(1)Bone marrow mesenchymal stem cells from osteoporotic SD rats and bone marrow monocytes from C57BL/6 mice were collected.MTT assay was used to detect different doses of Bushen Yiqi Huayu granule on bone mesenchymal stem cell toxicity.Bone mesenchymal stem cells and bone marrow monocytes were cultured in the medium supplemented with 0 and 1.5 mg/mL Bushen Yiqi Huayu granules,respectively,and osteogenic differentiation and osteoclast differentiation were carried out in vitro.(2)144 SD rats were randomly divided into sham operation group,model group,granule group and granule+PD98059 group with 36 rats in each group.The osteoporotic model was established in the model group,granule group and granule+PD98059 group,and only part of the adipose tissue near the ovary was removed in the sham operation group.8 weeks later,all rats received left tibial osteotomy.In the granule+PD98059 group,5 g/kg Bushen Yiqi Huayu granule was given intragastrically,and 0.3 mg/kg PD98059 was injected into the tail vein.The granule group was given 5 g/kg Bushen Yiqi Huayu granule,and the same volume of normal saline was injected into the tail vein.The sham operation group and model group were given an equal volume of normal saline,and the caudal vein was injected with an equal volume of normal saline.Drug administration was conducted once a day for 8 weeks.Fracture healing and callus angiogenesis were observed by X-ray,micro-computed tomography and microvascular perfusion angiography.Bone mineral density and mechanical strength of the callus were measured.The tibia was observed by hematoxylin-eosin staining and Masson staining.Western blot assay and immunohistochemistry were used to examine the expression of ERK/MAPK signaling pathway-related molecules. RESULTS AND CONCLUSION:(1)Compared with the 0 mg/mL group,the alkaline phosphatase activity,mineralization level,p-ERK1/2 and p-p38 MAPK expression levels of osteocytes increased(P<0.05),while the density and volume of osteoclasts decreased in the 1.5 mg/mL group(P<0.05).(2)Compared with the sham operation group,the fracture healing degree of the granule group was similar at 4 and 8 weeks,but there was no significant difference in Lane-Sandhu score,total callus volume,mineralized callus volume,mineralized callus volume/total callus volume,trabecular thickness,vascular number,spacing,thickness,vascular volume/total volume,bone mineral density,ultimate load of callus,stiffness,p-ERK1/2,p-p38 MAPK,p-IκB-α,and p-p65 expression levels(P>0.05).In the model group and granule+PD98059 group,fracture healing was slow,Lane-Sandhu score,total callus volume,mineralized callus volume,mineralized callus volume/total callus volume,trabecular thickness,vascular number,thickness,vascular volume/total volume,bone mineral density,ultimate load of callus,stiffness,p-ERK1/2,p-p38 MAPK,p-IκB-α,and p-p65 expression levels decreased(P<0.05),and vascular spacing increased(P<0.05),compared with the sham operation group.(3)It is indicated that Bushen Yiqi Huayu granule can improve fracture healing,promote callus angiogenesis and alleviate the symptoms of osteoporosis by enhancing the expression of the ERK/MAPK signaling pathway-related molecules in osteoporotic rats.