Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up.

To analyze the occurrence of early complications after total hip arthroplasty (THA) in patients with systemic lupus erythematosus (SLE).

Objective:To investigate the efficacy of a decellularized extracellular matrix (dECM)-quaternized chitosan (QCS)-gelatin (Gel) composite scaffold loaded with growth factors in repairing diabetic foot wounds in a rat model.Methods:A dECM-QCS-Gel composite scaffold (referred to as GDQ scaffold) was fabricated using a 3D bioprinter. Forty 8-week-old male Sprague-Dawley (SD) rats were selected to establish a diabetic foot wound model with a diameter of approximately 1 cm. Based on the treatment methods for diabetic foot wounds, the rats were divided into five groups: Control group (no treatment), Exosome group (wound covered with exosome suspension), Exosome+GDQ group (wound covered with GDQ scaffold loaded with exosome suspension), GDQ group (wound covered with GDQ scaffold alone), and Growth factor+GDQ group (wound covered with GDQ scaffold loaded with recombinant human basic fibroblast growth factor suspension). The wound healing rate was measured. Histological analysis was performed by HE staining and Masson staining. ELISA kits were used to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in wound tissues from each group. Protein expression levels of MIP-1 and MIP-2 genes were also assessed.Results:The wound healing rate of the growth factor+GDQ group on the 21st d was 94.89%±1.21%, which was higher than that of the exosome+GDQ group ( P<0.05). With increasing repair time, the expression levels of TNF-α, IL-1β and IL-6 in each group all decreased, while IL-10 increased in all groups ( P<0.05). Among them, the exosome+GDQ group (TNF-α: 46.54±1.26 pg/ml, IL-1β: 225.79±7.29 pg/ml, IL-6: 142.81±4.02 pg/ml and IL-10: 117.36±0.95 pg/ml, P<0.001) and the growth factor+GDQ group (TNF-α : 40.01±1.64 pg/ml, IL-1β: 209.15±2.98 pg/ml, IL-6: 138.50±2.61 pg/ml and IL-10: 127.66±1.23 pg/ml, P<0.05); The levels of TNF-α and IL-1β in the exosome+GDQ group were both lower than those in the exosome+GDQ group ( P<0.05), and IL-10 was higher than that in the exosome+GDQ group ( P<0.05). On the 7th d the control group showed the highest expression levels of MIP-1α and MIP-2. All other groups had lower levels, with the growth factor+GDQ group showing the lowest among them. On the 21st d, the inflammatory protein expression in the growth factor+GDQ group had further decreased and remained lower than in all other experimental groups. Conclusions:The GDQ composite scaffold, when combined with bioactive factors, can synergistically reduce inflammation in diabetic foot wounds and promote wound healing. The scaffold loaded with basic fibroblast growth factor demonstrated superior therapeutic efficacy compared to the scaffold loaded with exosomes.

Objective:To evaluate the therapeutic efficacy of an upper limb rehabilitation robot on the recovery of elbow function recovery following arthroscopic elbow joint release.Methods:Seventy-two patients who underwent arthroscopic elbow joint release at Shanghai Sixth People’s Hospital from December 2022 to December 2023 were recruited. All patients were randomly assigned to either the conventional group (n=36; 16 males, 20 females; age 34.39±9.04 years, range 24-56; fractures: 4 intercondylar humerus, 18 olecranon, 8 radial head, 6 other) which received conventional rehabilitation postoperatively, or the robot-assisted group (n=36; 18 males, 18 females; age 33.78±9.98 years, range 20-59; fractures distribution identical to the conventional group) receiving conventional rehabilitation combined with robot-assisted upper limb rehabilitation therapy. The active range of motion (ROM) of elbow joint, Mayo elbow performance score (MEPS), visual analogue scale (VAS) of elbow joint were recorded preoperatively and at 4 weeks and 3 months postoperatively. The surface electromyography were analyzed at 3 months postoperatively.Results:All patients completed the 3-month rehabilitation program. At 4 weeks postoperatively, the conventional group exhibited a mean active ROM of 106.78°±9.91°, MEPS of 67.78±7.68, VAS of 2.11±0.74; the robot-assisted group showed active ROM of 113.72°±7.06°, MEPS of 73.33±9.28, VAS of 21.89±0.46. By 3 months postoperatively, the conventional group achieved a mean active ROM of 118.11°±6.75°, MEPS of 85.00±8.66, VAS of 0.67±0.67; robot-assisted achieved a mean active ROM of 127.61°±6.61°, MEPS of 91.11±6.57, VAS of 0.39±0.49. Both groups exhibited significant improvements in active ROM and MEPS, and significant reductions in VAS scores at 4 weeks and 3 months postoperatively compared with preoperatively values ( P<0.05). The robot-assisted group demonstrated significantly higher active ROM and MEPS at both 4 weeks and 3 months postoperatively, and a significantly lower VAS score at 3 months postoperatively, compared with the conventional group ( P<0.05). Surface electromyography at 3 months revealed significantly higher biceps brachii root mean square and significantly lower co-contraction index in the robot-assisted group compared to the conventional group ( P<0.05). No adverse symptoms were reported in the treated elbows of either group during the operation and follow-up period. Conclusion:The integration of upper limb rehabilitation robot-assisted therapy and conventional rehabilitation program significantly enhances the recovery of elbow range of motion and functional outcomes at 3 months following arthroscopic elbow joint release.

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.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To summarize the surgical strategies and to evaluate the clinical outcomes of up-per urinary tract reconstruction in patients with stone-related ureteral strictures.Methods:This retro-spective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who un-derwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023.Patient data were collected,including demographic characteristics,clinical presen-tation,laboratory results,imaging findings,surgical procedures,and follow-up outcomes.Ureteral stric-tures were classified according to anatomical location into upper,middle,lower,or multiple segments.Surgical procedures were carried out depending on the stricture characteristics.Surgical success was de-fined as resolution or improvement of clinical symptoms,radiographic improvement or stabilization of hy-dronephrosis,and maintenance of normal and stable renal function.Results:Among the 71 patients,36(50.7％)had strictures in the upper ureter,9(12.7％)in the middle ureter,15(21.1％)in the lower ureter,and 11(15.5％)had multifocal ureteral strictures.The median stricture length was 5.0 cm(interquartile range:3.0-15.0 cm).Surgical approach selection was individualized based on the location and extent of the stricture.For upper ureteral strictures,the most frequently employed techniques were oral mucosal graft ureteroplasty(13/36,36.1％)and appendiceal flap ureteroplasty(8/36,22.2％).Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures.In middle ureteral strictures,treatment was stratified by length:balloon dilation(1/9,11.1％)and ureteroureterostomy(1/9,11.1％)were applied in shorter strictures,while oral mucosal graft ureteroplasty(3/9,33.3％)and ileal ureter replacement(4/9,44.4％)were reserved for longer segments.For lower ureteral strictures,ureteral reimplantation into the bladder was the most common approach(10/15,66.7％),often combined with a psoas hitch or Boari flap when necessary.All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease.The median follow-up period was 14.2 months(range:6.1-107.1 months).During follow-up,69 of 71 patients(97.2％)achieved surgical success.Conclusion:Stone-related ure-teral strictures present with considerable heterogeneity in terms of anatomical location,length,and com-plexity.Careful preoperative evaluation and individualized surgical planning are critical to successful re-construction.With appropriate selection of surgical methods,favorable long-term clinical outcomes can be achieved in the majority of patients.

OBJECTIVES: To explore the role of C1q, the promoter of the classical pathway of the complement system, in regulating postpartum depressive-like behaviors in mice and the therapeutic mechanism of C1q-neutralizing antibodies. METHODS: Female C57BL/6 mouse models of postpartum depression established by hormone-simulated pregnancy (HSP) were evaluated for depression-like behaviors, and peripheral blood levels and hippocampal expressions of C1q were detected using ELISA and Western blotting. Immunofluorescence staining was used for detecting co-labeling of C1q and microglia, and the differentially expressed mRNAs in the hippocampus of HSP mice were analyzed using RNA sequencing. The Edinburgh Postnatal Depression Scale was used to screen patients with postpartum depression, from whom peripheral blood mononuclear cells were extracted for detecting C1q expression levels with Western blotting. The HSP mice were subjected to stereotactic injection of C1q-neutralizing antibody or a control IgG in the hippocampus, and the changes in depressive-like behaviors and hippocampal expression of C3 were examined. RESULTS: The HSP mice exhibited obvious depressive behaviors, demonstrated by significantly decreased preference for sugar water and increased forced swimming and tail suspension time. The mouse models showed significantly increased peripheral blood C1q level and hippocampal expression level of C1q, accompanied by an increase in Iba1 and C1q co-labeling in the hippocampus. The expression level of C1q in peripheral monocytes was also significantly increased in patients with postpartum depression. In HSP mice, stereotactic injection of C1q-neutralizing antibody, but not the control IgG, obviously alleviated depressive-like behaviors, shown by significantly increased preference for sugar water and decreased forced swimming and tail suspension time, resulting also in decreased expression of C3 in the hippocampus and lowered serum levels of IL-6 and TNF-α. CONCLUSIONS C1q-neutralizing antibodies improve postpartum depressive-like behaviors in mice possibly by regulating the C1q/C3 signaling pathway.
Animals ; Female ; Depression, Postpartum ; Complement C1q/metabolism* ; Antibodies, Neutralizing/pharmacology* ; Mice, Inbred C57BL ; Mice ; Hippocampus/metabolism* ; Pregnancy ; Disease Models, Animal

Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*