Objective:To explore the clinical efficacy of anterolateral thigh perforator flap (ALTPF) in treatment of extensive wound of Degree IV burns in limbs.Methods:A retrospective analysis was conducted on 9 patients who had extensive wound of Degree IV burns in limbs caused by stove burns admitted to Department of Burns and Plastic Surgery, the 988th Hospital of the Joint Logistics Support Force of the Chinese PLA between January 2017 and January 2024. Among the patients, there were 8 males and 1 female, aged between 36 and 63 years. Three patients had the wound from anterior leg to dorsal foot, 3 from leg down to ankle, 1 from forearm to hand and 2 from arm to forearm. Area of burns ranged from 20 cm × 15 cm to 30 cm × 25 cm, and all patients were treated by free ALTPF. According to whether the main artery at the recipient site was feasible for direct anastomosis with the vessels carried in flap, 4 patients were treated by bilateral parallel ALTPFs, and 5 were treated by unilateral ultra-long internally supercharged ALTPF. A total of 13 ALTPFs were harvested, with individual flap size at 20 cm × 8 cm to 46 cm × 12 cm. Donor sites were directly sutured. Time for flap harvesting, flap survival and wound healing time were records. Scheduled postoperative follow-up was conducted at outpatient clinic and via telephone interviews to evaluate functional recovery. Follow-up assessments included evaluation of flap condition, two-point discrimination (TPD), recovery of joint function at recipient sites, flap appearance and donor site recovery.Results:The time for flap harvest was 1.0 to 4.5 hours. All 13 ALTPFs successfully survived. The time from surgery to healing of recipient sites was 18 to 72 days, and all donor sites healed. Over the postoperative follow-up that lasted for 6 to 34 months, the recipient sites had found with good cosmetic outcomes, without osteomyelitis or deep tissue infection. Four ALTPFs in 2 patients were found swelling, which were revised at 6 months after surgery. Four ALTPFs in other 2 patients had pigment deposition at edges. One ALTPF was scalded, which healed after dressing changes but left with patchy scars. The remaining ALTPFs were soft, elastic, free from pain and well-perfused, with regained protective sensation at S 3. However, all of the ALTPFs failed to detect TPD. Six patients with lower limb injuries were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scoring system: 2 patients were rated as excellent and 4 were rated as good. Three patients with upper limb injuries were evaluated using Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association: 1 patient was rated as excellent and 2 were rated as good. Only linear scars left at the 13 donor sites, with normal blood supply to the distal limbs, and without restrictions in range of motion of knee joints nor muscle strength of quadriceps. Conclusion:The ALTPF offers advantages such as anatomical consistency, reliable blood supply and flexible combination in treatment of extensive wound of Degree Ⅳ burns in limbs. It is an ideal surgical procedure for treatment of large soft tissue defects of extremities.

Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

Objective:To explore the clinical efficacy of anterolateral thigh perforator flap (ALTPF) in treatment of extensive wound of Degree IV burns in limbs.Methods:A retrospective analysis was conducted on 9 patients who had extensive wound of Degree IV burns in limbs caused by stove burns admitted to Department of Burns and Plastic Surgery, the 988th Hospital of the Joint Logistics Support Force of the Chinese PLA between January 2017 and January 2024. Among the patients, there were 8 males and 1 female, aged between 36 and 63 years. Three patients had the wound from anterior leg to dorsal foot, 3 from leg down to ankle, 1 from forearm to hand and 2 from arm to forearm. Area of burns ranged from 20 cm × 15 cm to 30 cm × 25 cm, and all patients were treated by free ALTPF. According to whether the main artery at the recipient site was feasible for direct anastomosis with the vessels carried in flap, 4 patients were treated by bilateral parallel ALTPFs, and 5 were treated by unilateral ultra-long internally supercharged ALTPF. A total of 13 ALTPFs were harvested, with individual flap size at 20 cm × 8 cm to 46 cm × 12 cm. Donor sites were directly sutured. Time for flap harvesting, flap survival and wound healing time were records. Scheduled postoperative follow-up was conducted at outpatient clinic and via telephone interviews to evaluate functional recovery. Follow-up assessments included evaluation of flap condition, two-point discrimination (TPD), recovery of joint function at recipient sites, flap appearance and donor site recovery.Results:The time for flap harvest was 1.0 to 4.5 hours. All 13 ALTPFs successfully survived. The time from surgery to healing of recipient sites was 18 to 72 days, and all donor sites healed. Over the postoperative follow-up that lasted for 6 to 34 months, the recipient sites had found with good cosmetic outcomes, without osteomyelitis or deep tissue infection. Four ALTPFs in 2 patients were found swelling, which were revised at 6 months after surgery. Four ALTPFs in other 2 patients had pigment deposition at edges. One ALTPF was scalded, which healed after dressing changes but left with patchy scars. The remaining ALTPFs were soft, elastic, free from pain and well-perfused, with regained protective sensation at S 3. However, all of the ALTPFs failed to detect TPD. Six patients with lower limb injuries were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scoring system: 2 patients were rated as excellent and 4 were rated as good. Three patients with upper limb injuries were evaluated using Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association: 1 patient was rated as excellent and 2 were rated as good. Only linear scars left at the 13 donor sites, with normal blood supply to the distal limbs, and without restrictions in range of motion of knee joints nor muscle strength of quadriceps. Conclusion:The ALTPF offers advantages such as anatomical consistency, reliable blood supply and flexible combination in treatment of extensive wound of Degree Ⅳ burns in limbs. It is an ideal surgical procedure for treatment of large soft tissue defects of extremities.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The ubiquitin-specific peptidase 25 (USP25) protein has been reported to participate in the development of several cancers. However, few studies have reported its association with HCC. In this study, we aimed to investigate the function and mechanism of USP25 in the progression of HCC. METHODS: We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database cohorts. Then, we constructed USP25-overexpressing and USP25-knockdown HepG2, MHCC97H, and L-O2 cells. We detected the biological function of USP25 by performing a series of assays, such as Cell Counting Kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway. The relationship between USP25 and tripartite motif-containing 21 (TRIM21) was assessed through mass spectrometry and co-immunoprecipitation (Co-IP) analysis. Finally, we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25. RESULTS: USP25 was highly expressed in HCC tissue and HCC cell lines. Importantly, high expression of USP25 in tissues was closely related to a poor prognosis. USP25 knockdown markedly reduced the proliferation, migration, and invasion of HepG2 and MHCC97H cells, whereas USP25 overexpression led to the opposite effects. In addition, we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial-mesenchymal transition (EMT; E-cadherin, N-cadherin, and Snail) and the Wnt/β-catenin pathway (β-catenin, Adenomatous polyposis coli, Axin2 and Glycogen synthase kinase 3 beta) and those of their downstream proteins (C-myc and Cyclin D1). Finally, we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo . CONCLUSIONS In summary, our data showed that USP25 was overexpressed in HCC. USP25 promoted the proliferation, migration, invasion, and EMT of HCC cells by interacting with TRIM21 to activate the β-catenin signaling pathway.
Animals ; Mice ; beta Catenin/genetics* ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic ; Liver Neoplasms/pathology* ; Ubiquitin Thiolesterase/metabolism* ; Wnt Signaling Pathway/genetics*

【Objective】 To evaluate the expression of GAB1 in ER-positive breast cancer and its effect on MCF-7 cells’ metastasis. 【Methods】 The expression of GAB1 in ER-positive breast cancer tissues was detected by immunohistochemistry. We analyzed the relationship of GAB1 expression with the patients’ clinicopathological features and prognosis. The invasion and metastasis abilities of MCF-7 cells after silencing GAB1 expression were observed by Transwell assay. The effect of GAB1 expression on the EMT of breast cancer cells was analyzed by Western blotting. 【Results】 Immunohistochemical staining showed that GAB1 expression had significant correlation with lymph node metastasis(P=0.014) and stage(P=0.011). Transwell results showed that shGAB1 significantly inhibited the migration and invasion of human breast cancer MCF-7 cells. Western blotting results showed that shGAB1 significantly increased E-cadherin expression and decreased Vimentin expression. Kaplan-Meier analysis revealed that ER-positive breast cancer patients with high GAB1 expression tumors had a significantly worse relapse-free survival rate than those with low GAB1 expression tumors(P<0.001). Multivariate analysis showed that stage and GAB1 expression were independent predictors of survival. 【Conclusion】 GAB1 is highly expressed in ER-positive breast cancer. ShGAB1 expression can inhibit the migration, invasion and EMT of breast cancer cells. GAB1 might be used as one of the valuable markers for prognosis in patients with ER-positive breast cancer.

Objectives: To explore and summarize the beneficial effects of a traditional Chinese medicine prepara-tion, Tripterygium glycosides tablets (TGT), in rheumatoid arthritis (RA) animal models of neo-vascularization, and to provide a reference for future clinical applications and research on its pharmacologic mechanism.Methods: We searched the databases PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, VIP, Wan Fang and SinoMed (China Biomedical Document Service System) to identify studies of TGT with outcome indicators of angiogenesis-related factors that were published before April 2020. Subgroup analysis and meta-regression were performed for dosage and duration of TGT. Statistical tests and subgroup analysis were conducted using RevMan 5.3, and meta-regression and sensitivity analysis were conducted using STATA/SE 15.0. Results: Fourteen studies of TGT in RA rats were included in this analysis. Treatment with TGT signifi-cantly reduces synovial microvessel density and the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, hypoxia inducible factor α, c-Fos, c-Jun, angiopoietin-1 and angiopoietin-2 compared with control groups (P < .05). Subgroup analysis did not show a significant association of the mRNA levels of VEGF in synovium, assessed using quantitative real-time PCR, with duration or dosage of TGT. Meta-regression analysis also indicated that the effects of dosage and duration were not significantly associated with differences in VEGF mRNA levels. Sensitivity analysis on VEGF mRNA levels did not fundamentally change the results. Conclusions: TGT can reduce synovial neovascularization by decreasing synovial microvessel density and expression of VEGF, VEGF receptor 2, hypoxia-inducible factorα, c-Fos, c-Jun, Ang-1 and Ang-2, thereby suppressing pannus formation and bone destruction in rat models of RA. Additional well-designed studies are required to confirm these findings.

Objective To observe the efficacy and safety of apatinib combined with docetaxel in the third line and above treatment of advanced serum alpha-fetoprotein-positive gastric cancer(AFPGC). Methods A total of 41 patients with AFPGC from February 2015 to April 2018 in Suining Central Hospital of Sichuan Province were retrospectively analyzed. The patients were divided into experimental group and control group according to different treatment methods,15 patients in the experimental group received with apatinib combined with docetaxel,and 26 patients in the control group received chemotherapy alone or optimal nutritional support. The short-term efficacy,long-term efficacy and adverse reactions were evaluated by Response Evaluation Criteria in Solid Tumours(RECIST)version 1. 1,progression-free survival(PFS),overall survival(OS)and National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE)version 4. 0. Results After 2 cycles of treatment,no complete remission( CR)was achieved in either group,4 partial remission (PR),7 stable disease(SD),4 progressive disease(PD)in the experimental group,and 2 PR,7 SD,17 PD in the control group. The objective response rate(ORR)was 26. 67％(4 / 15)and 7. 69％(2 / 26)respective-ly in the experimental group and the control group,with no significant difference(χ2 = 1. 433,P = 0. 231). The disease control rate(DCR)was 73. 33％(11 / 15)and 34. 62％(9 / 26)respectively in the two groups, with significant difference(χ2 = 5. 707,P = 0. 017). The median PFS of the experimental group and the control group were both 3. 0 months,and there was no significant difference between the two groups(χ2 = 4. 425,P =0. 350). The median OS were 6. 0 months and 4. 0 months respectively,and the difference was statistically sig-nificant(χ2 = 5. 727,P = 0. 017). The occurrence rates of leukopenia of the experimental group and the control group were 73. 33％(11 / 15)and 30. 77％(8 / 26),the occurrence rates of hypertension were 40. 00％(6 /15)and 0(0 / 26),the occurrence rates of proteinuria were 26. 67％(4 / 15)and 0(0 / 26),the occurrence rates of poor appetite were 80. 00％(12 / 15)and 38. 46％(10 / 26),and the occurrence rates of hemorrhage were 33. 33％(5 / 15)and 3. 85％(1 / 26). The occurrence rates of the above adverse reactions in the experi-mental group were significantly higher than those in the control group(χ2 = 6. 930,P = 0. 008;χ2 = 9. 191, P = 0. 002;χ2 = 4. 953,P = 0. 026;χ2 = 6. 600,P = 0. 010;χ2 = 4. 471,P = 0. 034),and the differences were statistically significant. There was no significant difference in the incidence of thrombocytopenia,anemia, nausea and vomiting,diarrhea,fatigue and hand-foot syndrome between the two groups( all P > 0. 05). Conclusion The DCR of apatinib combined with docetaxel in the third-line and above treatment of advanced AFPGC patients is higher. This scheme can prolong survival period,and the adverse reactions are more serious,but they are basically tolerable.

Sepsis is frequently associated with multi-system organ dysfunction and refractory hypotension,leading to a high mortality and poor prognosis.As an antioxidant,ascorbic acid (vitamin C) is an important auxiliary factor for many enzymes in the organism.Numerous studies have revealed that vitamin C can attenuate the inflammatory response,improve microcirculatory and hypotension in sepsis,and also can enhance the role of catecholamine in central nervous system,to prevent sepsis-induced organ failure and improve prognosis of patients.

This study was aimed to analyze the application of non-pharmacotherapy in treating cervical radiculopathy (CR) in real-world,and to provide clinical reference for CR non-pharmacotherapy.The clinical real-world data of CR was extracted by using information sharing system of traditional Chinese medicine (TCM) and clinical research.Six hundred and twenty-eight inpatients and outpatients with CR were enrolled from December 2012 to July 2014 in the information system database of Wangjing Hospital.Basic characteristics of the non-pharmacotherapy groups were analyzed by statistical description method.The node degree and mutual information value were recorded for non-pharmacotherapy application of all patients by using liquorice software.Complex network diagrams were generated.The results showed that 47％ of CR patients received non-pharmacotherapy (294/628),including 67 males and 227 females.The average age of patients was 49 years old,and the prevalence of the disease was the highest from 45 to 65 years old.In all patients,the usage of manipulation and cervical traction was higher,and the combination of manipulation and acupuncture was the most.Within outpatients,the proportion of cervical traction was higher,and the combination of manipulation and acupuncture was the most frequently.Within inpatients,the proportion of manipulation and cervical traction was higher,and the combination of comprehensive physical therapy and exercise therapy was the most frequently.It was concluded that non-pharmacotherapy has been commonly used in clinical treatment of CR.Cervical traction and manipulation was the widest applications.The combination treatment was in wide application.Future studies should increase the sample size of CR patients from different regions,and enhance gradually the level of evidence of clinical research for non-pharmacotherapy treating CR.