ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

BackgroundResident physicians represent a high-risk group for sleep disorders， exhibiting a significantly higher prevalence of such conditions compared with the general population， which severely impairs their physical and mental health. It is hypothesized that perceived stress negatively impacts sleep quality through psychological mechanisms， such as depleting self-control resources and triggering anxiety. However， this pathway warrants empirical validation. ObjectiveTo explore the mediating role of self-control and anxiety emotions in the association between perceived stress and sleep quality among resident physicians， and to elucidate the underlying psychological mechanisms， aiming at providing theoretical basis for developing targeted psychological interventions. MethodsA cross-sectional survey was conducted in April 2025. First- to third- year resident physicians at a hospital in Fuyang City were recruited as participants （n=372）. The Chinese Perceived Stress Scales （CPSS）， the Chinese version of the Dual-Mode of Self-Control Scale （DMSC-S）， the Pittsburgh Sleep Quality Index （PSQI）， and the Generalized Anxiety Disorder Scale-7 item （GAD-7） were used for group testing. The model 6 of the Process macro version 4.1 was ultilized to examine the mediating pathway of self-control and anxiety emotions between perceived stress and sleep quality. ResultsA total of 322 valid questionnaires were collected， yielding an effective responsive rate of 86.56%. Among the respondents， 146 （45.34%） reported poor sleep quality. The CPSS score and GAD-7 score of resident physicians were positively correlated with the PSQI score （r=0.727， 0.784， P<0.01）， while the DMSC-S score was negatively correlated with the PSQI score （r=-0.615， P<0.01）. Perceived stress directly and positively predicted poor sleep quality （B=0.124， P<0.01）， with the direct effect accounting for 31.39% of the total effect. Furthermore， perceived stress indirectly affected sleep quality through the independent mediating effects of self-control and anxiety emotions. The indirect effect values of 0.053 （95% CI： 0.019 - 0.091） and 0.192 （95% CI： 0.141 - 0.249）， accounting for 13.42% and 48.61% of the total effect， respectively. Perceived stress also impact sleep quality through the serial mediating effect of self-control and anxiety， with the indirect effect value of 0.026 （95% CI： 0.005 - 0.049）， accounting for 6.58% of the total effect. ConclusionThe perceived stress of resident physicians can influence sleep quality by impairing self-control， exacerbating anxiety， and through the serial mediation of both factors.

Objective To compare the performance of 7 Chinese-developed GenAI models (DeepSeek, Wenxin Yiyan, Tongyi, Doubao, Kimi, Hunyuan, and iFLYTEK Spark) in responding to common diseases of the pediatric genitourinary system and to explore their potential applications.Methods A total of 80 questions covering basic disease information, diagnosis, treatment, and prognosis related to “hypospadias, hydronephrosis, and cryptorchidism” were developed as prompts.The models were tested under 3 modes:“quick thinking, ”“deep thinking, ” and “deep thinking + internet access.” The results were evaluated in a blinded review by two pediatric urologists.The responses were graded into 4 levels—A, B, C, and D—based on accuracy, completeness, and relevance.The proportions of responses rated as A and A+B were statistically analyzed and compared across the different models/modes.Results The “deep thinking” mode of DeepSeek demonstrated the best performance, with 88% of responses rated as A and 96% rated as A+B.DeepSeek (deep thinking + internet access), Doubao (quick thinking), Hunyuan (deep thinking), and Doubao (deep thinking + internet access) followed closely, also showing excellent response capabilities.Among the top 5 models/modes, significant differences were observed in the proportion of Alevel responses (P＜0.05), while differences in the proportion of A+B-level responses were not statistically significant (P＞0.05).Conclusion Certain Chinese-developed GenAI models, represented by DeepSeek (deep thinking), demonstrate significant application potential.However, they still cannot consistently provide recommendations rated at the A+B level (recommended grade or higher) with 100% accuracy.In clinical practice, both doctors and patients should view GenAI as an auxiliary tool for education and information acquisition rather than as a final decision-making authority.All information must be reviewed and confirmed by professional physicians.

Objective To compare the clinical efficacy and safety of transarterial chemoembolization(TACE)plus apatinib(Apa)and camrelizumab(Cam)and TACE plus Apa in treating CNLC stage Ⅲ hepatocellular carcinoma(HCC).Methods A total of 54 patients in Affiliated Yancheng No.1 People's Hospital,School of Medicine,Nanjing University with CNLC stage Ⅲ HCC were enrolled in this study.The patients were divided into triple treatment group(n=25,receiving TACE plus Apa and Cam)and dual treatment group(n=29,receiving TACE plus Apa).The overall survival(OS)and progression-free survival(PFS)were compared between the two groups.Univariate analysis and multivariate analysis were used to determine the independent influencing factors for OS and PFS.The target immunotherapy-related adverse reactions(TRAE)were analyzed.Results The median OS and PFS in the triple treatment group were 23.2 months and 10.9 months respectively,which were higher than 15.2 months and 5.8 months respectively in the dual treatment group(both P＜0.001).Multivariate analysis indicated that the therapeutic regimen and the type of portal vein tumor thrombosis(PVTT)were the independent factors affecting OS,while only the therapeutic regimen was the independent factor affecting PFS.The incidence of≥grade Ⅲ TRAE in the triple treatment group and the dual treatment group was 20％(5/25)and 17.2％(5/29)respectively,the difference between the two groups was not statistically significant(P＞0.05).Conclusion For the treatment of patients with CNLC stage Ⅲ HCC,TACE plus Apa and Cam is superior to TACE plus Apa in OS and PFS,and the type of PVTT and the therapeutic regimen are the independent prognostic factors associated with patient's survival.

We report a case of a 14-year-old male with first metatarsocuneiform coalition. With a 1-month history of left foot pain the patient presented to some hospital 8 months ago, where conservative management, including rest, physiotherapy, and medication, was administered. However, symptoms gradually worsened. On admission to our hospital, radiograph revealed a bony bridge at the left first metatarsocuneiform joint, which had enlarged compared with the radiograph 8 months earlier. The patient was diagnosed as first metatarsocuneiform coalition in the left foot and underwent resection of the bony bridge, followed by plaster immobilization for 3 weeks. At 3 months postoperatively, he had resumed normal activity without pain or discomfort. First metatarsocuneiform coalition is a rare type of tarsal coalition. Currently, there are no standardized surgical indications or established treatment protocols. Given the uncertainty of surgical outcomes, conservative treatment should be the primary choice. Surgical intervention may be considered when conservative measures fail or symptoms continue to worsen.

Objective:To evaluate the relationship between the mechanism of mild hypothermia-induced reduction of neuronal apoptosis during cerebral ischemia-reperfusion (I/R) and calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in rats.Methods:Forty SPF male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 5 groups ( n=8 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (IR group), hypothermia + cerebral I/R group (HIR group), hypothermia + cerebral ischemia-reperfusion + solvent group (HIR-DMSO group) and hypothermia + ischemia-reperfusion + CaMKK2 inhibitor STO-609 group (HIR-STO609 group). A global cerebral I/R injury model was established using the four-vessel occlusion method. In HIR group, HIR-DMSO group, and HIR-STO609 group, an ice blanket was used to reduce the body temperature immediately after cerebral ischemia, bringing the core body temperature down to 32.5-33.5 ℃, and rewarming was carried out 4 h later. One hour before developing the model, STO-609 solution 4 μl was injected into the lateral ventricle in HIR-STO609 group, and the equal volume of dimethyl sulfoxide solution was given instead in HIR-DMSO group. At the end of reperfusion, the modified neurological severity score (mNSS) was performed. Then the rats were sacrificed under deep anesthesia, and the hippocampal tissues were taken to observe the pathological results of the hippocampal tissues (using HE staining and Nissl staining) and to determine the apoptosis rate of neurons (by TUNEL method) and expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X (Bax), CaMKK2, phosphorylated AMPK (p-AMPK) and AMPK (by Western blot). Results:Compared with Sham group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly increased, the expression of Bax was up-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was down-regulated, and the ratio of p-AMPK/AMPK was decreased in IR group ( P<0.05). Compared with IR group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly decreased, the expression of Bax was down-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was up-regulated, and the ratio of p-AMPK/AMPK was increased in HIR group ( P<0.05). Compared with HIR group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly increased, the expression of Bax was up-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was down-regulated, the ratio of p-AMPK/AMPK was decreased ( P<0.05), and no significant change was found in the aforementioned parameters in HIR-DMSO group ( P>0.05). Conclusions:Mild hypothermia can inhibit neuronal apoptosis by up-regulating the CaMKK2/AMPK signaling pathway, thus reducing cerebral I/R injury in rats.

Objective:To investigate a surgical method and clinical effect on reconstruction of infective ulcer and soft tissue defects in dorsal fingers of the elderly patients with free perforator flap of peroneal artery.Methods:From March 2016 to June 2022, 13 elderly patients with infective ulcer and soft tissue defects in dorsal fingers were reconstructed with free perforator flaps of peroneal artery. The patients were 65-70 years with an average age of 66.5 years. Cause of infection: 10 ulceration and soft tissue defects were caused by diabetes and 3 by injury. Seven infective ulceration and soft tissue defects were in dorsal index fingers, 3 in dorsal middle fingers and 3 in dorsal ring fingers with the size of soft tissue defects at 2.0 cm×4.5 cm-2.0 cm×5.5 cm with an exposure of tendon and phalange. The donor site of the flaps was of contralateral calf and the flaps were 2.5 cm×5.0 cm-2.5 cm×6.0 cm in size. All donor sites were sutured directly. All patients were included in the postoperative follow-up at outpatient clinic to observe the appearance and sensation of the flap as well as finger movement.Results:All flaps survived and all wounds achieved stage I healing, without recurrence of infection. Twelve patients had the postoperative follow-up for 12 to 27 months, with an average of 21.6 months. There were satisfactory appearance of flaps and the function of fingers. Sensation of flaps recovered to S 2 in 5 patients and S 3 in 7 patients. The recovery of hand function was evaluated according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, with 8 hands in excellent and 4 in good. Conclusion:The free perforator flap of peroneal artery has advantages of constant vascular anatomy, reliable blood supply, moderate thickness and direct closure of donor site. It is a useful clinical method in reconstruction of infective ulcer and soft tissue defects in dorsal fingers of the elderly patients.

Objective:To explore the therapeutic effect of micro-flaps carrying sensory nerve in treatment of high-pressure injection injuries of the digit (HPIID).Methods:From January 2022 to June 2024, retrospective analysis of 7 patients who had HPIID were admitted to the Department of Hand Surgery Division 1, Norinco General Hospital. The patients were 5 males and 2 females with ages from 25 to 59 years. The digital injuries were: 3 index fingers, 2 middle fingers and 2 thumbs. All patients received debridement under microscope in primary surgery, with the defects at 1.5 cm×2.4 cm - 2.5 cm×5.5 cm in size after debridement. In stage Ⅱ surgery, 5 patients received the treatment of free fibular great toe flap carrying peroneal nerve of the great toe, with the flap size at 1.8 cm× 2.0 cm - 2.7 cm×4.0 cm. Two patients received the treatment of transfer of free fibular medial plantar flap carrying medial plantar nerve, with flap size at 1.9 cm×2.6 cm - 4.5 cm×5.7 cm. Donor sites were directly sutured in 5 patients, and 2 patients received skin grafting. Five patients received postoperative follow-up at outpatient clinic, 1 patient via telephone interview and 1 via WeChat review.Results:All 7 flaps survived and all wounds had primary healing. All donor and recipient sites and skin grafting sites healed primarily. Postoperative follow-up lasted for 4 to 9 months, with an average of 6.4 months. All the affected digits had satisfactory appearance and function, except 1 which was slightly slimmer than the healthy side. Range of motion of the affected digits was evaluated according to total active movement (TAM): 5 were in excellent and 2 in good. Sensory recovery of the digits was evaluated according to the British Medical Research Council (BMRC): 1 digit was at S 2, 2 at S 3 and 4 at S 4. One patient had two-point discrimination (TPD) at 9.0-15.0 mm, 2 at 6.0-10.0 mm, and 4 at 3.0-6.0 mm. Conclusion:For HPIID with a defect, surgical treatment with transfer of micro-flap carrying sensory nerve should be a preferred treatment option.

OBJECTIVE: To summarize the effectiveness of orthopedic surgery for patients with moderate and severe hallux valgus and analyze its related influencing factors. METHODS: A clinical data of 247 patients (287 feet) with moderate and severe hallux valgus, who were admitted between January 2013 and October 2024 and met the selection criteria, was retrospectively analyzed. There were 39 males and 208 females, with a median age of 57 years (range, 19-89 years). There were 207 cases of single-foot involvement and 40 cases of double-foot involvement; 159 feet were moderate hallux valgus and 128 feet were severe hallux valgus. The disease duration ranged from 3 months to 25 years, with a median of 5 years and 8 months. The hallux valgus angle (HVA), the intermetatarsal angle (IMA), proximal articular set angle (PASA), and the American Orthopaedic Foot and Ankle Society (AOFAS) scores were measured before operation and at 6 months after operation, and the differences (change values) between pre- and post-operation were calculated. All patients were grouped according to the degree of preoperative hallux valgus deformity and age, and the patients with severe hallux valgus according to different surgical procedures, and the change values of HVA, IMA, and AOFAS scores were compared between groups. All patients were grouped according to postoperative HVA, then the postoperative AOFAS scores were compared between groups. RESULTS: All patients successfully completed the operations and were followed up 6 months to 11 years and 3 months, with an average of 4 years and 6 months. The HVA, IMA, PASA, and AOFAS scores at 6 months after operation showed significant improvement compared to preoperative levels, and the differences were significant ( P<0.05). The patients with severe hallux valgus had the higher change values of HVA, IMA, and AOFAS scores than the patients with moderate hallux valgus ( P<0.05). The elderly patients had the highest change values of HVA and AOFAS scores than the young and middle-aged patients ( P<0.05). The patients with postoperative HVA ranging from 0° to 5° had the highest AOFAS scores than the other patients at 6 months after operation ( P<0.05). Among different surgical procedures for severe hallux valgus, the metatarsophalangeal joint fusion had the highest change value of HVA, the Scarf osteotomy had the highest performance in correcting the IMA, and the first metatarsal base osteotomy had the highest improvement in the postoperative AOFAS score, and the differences were significant ( P<0.05). CONCLUSION Elderly patients show the better improvement in HVA and foot function after operation. The first metatarsal base osteotomy show the better improvement in foot function than other surgical procedures. A certain HVA is allowed to remain after hallux valgus correction, and the postoperative AOFAS score is higher when the corrected HVA is in the range of 0°-5°.
Humans ; Hallux Valgus/diagnostic imaging* ; Middle Aged ; Male ; Female ; Aged ; Retrospective Studies ; Adult ; Aged, 80 and over ; Treatment Outcome ; Osteotomy/methods* ; Severity of Illness Index ; Orthopedic Procedures/methods* ; Metatarsophalangeal Joint/surgery* ; Young Adult ; Metatarsal Bones/surgery*