Objective:To investigate the effects and mechanisms of capsaicin on full-thickness skin defects in diabetic mice.Methods:This study was an experimental study. Thirty-six male db/db mice aged 6-8 weeks were taken. Circular full-thickness skin defect wounds (6 mm in diameter) were created on their backs. According to the random number table method (grouping method same below), the mice were divided into control group, low-concentration capsaicin group, and high-concentration capsaicin group injected with normal saline, 10 μmol/L capsaicin solution, and 20 μmol/L capsaicin solution, respectively ( n=12). Immediately after modeling and on day 2, 30 μL of the corresponding solution was injected locally into the wounds. At 4, 8, and 12 days after injury, wound healing status was observed grossly and the percentage of residual wound area was calculated. At 12 days after injury, the proportions of inflammatory cell, collagen fiber, and CD31-positive expression areas in the wound of mice were observed and detected respectively using hematoxylin and eosin staining, Masson staining, and immunohistochemical staining, and the protein expression of transient receptor potential vanilloid type 1 (TRPV1) in the wound tissue of mice was detected using Western blotting. Human primary fibroblasts were prepared from normal skin tissue obtained from 5 patients (2 male and 3 female patients, aged 20-45 years) who were admitted to the Department of Plastic and Reconstructive Surgery of Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine in October 2024. Cells in the logarithmic growth phase (passages 2-5) were used for subsequent experiments. Cells were divided into control group and high-concentration capsaicin group, cultured in complete media without or with 20 μmol/L capsaicin, respectively. After 24 hours of culture, differentially expressed genes (DEGs) between two groups were identified using the DESeq2 R package, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The cells were divided into control group, low-concentration capsaicin group, and high-concentration capsaicin group, which were cultured in complete media without capsaicin, and with 10 μmol/L capsaicin, and with 20 μmol/L capsaicin, respectively. After 48 hours of culture, cell apoptosis status was assessed using flow cytometer. The protein expression levels of protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) in cells were detected by Western blotting, and the p-Akt/Akt and p-mTOR/mTOR ratios were calculated. At 12 days after injury, the protein expression levels of Akt, p-Akt, mTOR, and p-mTOR in the wounds of diabetic mice in both control group and high-concentration capsaicin group were detected by Western blotting, and the p-Akt/Akt and p-mTOR/mTOR ratios were calculated. All animal experiments used a sample size of 6, and all cellular experiments used 3. Results:At 4 days after injury, the wounds of three groups of diabetic mice began to heal gradually, and the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 2.31 and 2.87, respectively, P<0.05). At 8 days after injury, the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 2.55 and 5.38, respectively, P<0.05). At 12 days after injury, the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group remained significantly lower than that in control group (with t values of 3.31 and 6.24, respectively, P<0.05), with the high-concentration capsaicin group showing a significantly greater reduction compared to that in low-concentration capsaicin group ( t=3.42, P<0.05). At 12 days after injury, the proportion of inflammatory cell area in the wound of mice in high-concentration capsaicin group was (6.2±1.8)%, significantly lower than (15.5±3.0)% in control group ( t=6.45, P<0.05). The proportion of collagen fiber area, proportion of CD31-positive expression area, and protein expression of TRPV1 in the wound of mice in high-concentration capsaicin group were significantly higher compared with those in control group (with t values of 5.48, 7.11, and 15.41, respectively, P<0.05). After 24 hours of culture, 51 DEGs with significantly differential expression were detected in high-concentration capsaicin group of cells compared with those in control group ( P<0.05), with 31 upregulated and 20 downregulated genes. GO analysis showed that the significantly upregulated and significantly downregulated DEGs mainly participated in biological processes such as extracellular matrix (ECM) polymerization, extracellular structure organization, collagen metabolic process regulation, and ECM component secretion regulation. KEGG analysis showed that the significantly upregulated and significantly downregulated DEGs mainly participated in cell apoptosis-related pathways such as the phosphatidylinositol 3-kinase/Akt pathway and tumor necrosis factor signaling pathway. After 48 hours of culture, the cell apoptosis rates in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 6.38 and 9.09, respectively, P<0.05). The p-mTOR/mTOR ratio in cells in low-concentration capsaicin group was significantly higher than that in control group ( t=2.74, P<0.05). The p-Akt/Akt and p-mTOR/mTOR ratios in cells in high-concentration capsaicin group were significantly higher than those in control group (with t values of 4.43 and 3.33, respectively, P<0.05). At 12 days after injury, the p-Akt/Akt and p-mTOR/mTOR ratios in wounds of diabetic mice in high-concentration capsaicin group were 0.470±0.044 and 0.549±0.106, respectively, which were significantly higher than 0.189±0.058 and 0.241±0.120 in control group (with t values of 6.67 and 3.36, respectively, P<0.05). Conclusions:Capsaicin can promote the healing of full-thickness skin defect wounds in diabetic mice by activating the Akt/mTOR signaling pathway in fibroblasts, thereby inhibiting apoptosis.

Objective:To investigate the effects and mechanisms of capsaicin on full-thickness skin defects in diabetic mice.Methods:This study was an experimental study. Thirty-six male db/db mice aged 6-8 weeks were taken. Circular full-thickness skin defect wounds (6 mm in diameter) were created on their backs. According to the random number table method (grouping method same below), the mice were divided into control group, low-concentration capsaicin group, and high-concentration capsaicin group injected with normal saline, 10 μmol/L capsaicin solution, and 20 μmol/L capsaicin solution, respectively ( n=12). Immediately after modeling and on day 2, 30 μL of the corresponding solution was injected locally into the wounds. At 4, 8, and 12 days after injury, wound healing status was observed grossly and the percentage of residual wound area was calculated. At 12 days after injury, the proportions of inflammatory cell, collagen fiber, and CD31-positive expression areas in the wound of mice were observed and detected respectively using hematoxylin and eosin staining, Masson staining, and immunohistochemical staining, and the protein expression of transient receptor potential vanilloid type 1 (TRPV1) in the wound tissue of mice was detected using Western blotting. Human primary fibroblasts were prepared from normal skin tissue obtained from 5 patients (2 male and 3 female patients, aged 20-45 years) who were admitted to the Department of Plastic and Reconstructive Surgery of Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine in October 2024. Cells in the logarithmic growth phase (passages 2-5) were used for subsequent experiments. Cells were divided into control group and high-concentration capsaicin group, cultured in complete media without or with 20 μmol/L capsaicin, respectively. After 24 hours of culture, differentially expressed genes (DEGs) between two groups were identified using the DESeq2 R package, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The cells were divided into control group, low-concentration capsaicin group, and high-concentration capsaicin group, which were cultured in complete media without capsaicin, and with 10 μmol/L capsaicin, and with 20 μmol/L capsaicin, respectively. After 48 hours of culture, cell apoptosis status was assessed using flow cytometer. The protein expression levels of protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) in cells were detected by Western blotting, and the p-Akt/Akt and p-mTOR/mTOR ratios were calculated. At 12 days after injury, the protein expression levels of Akt, p-Akt, mTOR, and p-mTOR in the wounds of diabetic mice in both control group and high-concentration capsaicin group were detected by Western blotting, and the p-Akt/Akt and p-mTOR/mTOR ratios were calculated. All animal experiments used a sample size of 6, and all cellular experiments used 3. Results:At 4 days after injury, the wounds of three groups of diabetic mice began to heal gradually, and the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 2.31 and 2.87, respectively, P<0.05). At 8 days after injury, the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 2.55 and 5.38, respectively, P<0.05). At 12 days after injury, the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group remained significantly lower than that in control group (with t values of 3.31 and 6.24, respectively, P<0.05), with the high-concentration capsaicin group showing a significantly greater reduction compared to that in low-concentration capsaicin group ( t=3.42, P<0.05). At 12 days after injury, the proportion of inflammatory cell area in the wound of mice in high-concentration capsaicin group was (6.2±1.8)%, significantly lower than (15.5±3.0)% in control group ( t=6.45, P<0.05). The proportion of collagen fiber area, proportion of CD31-positive expression area, and protein expression of TRPV1 in the wound of mice in high-concentration capsaicin group were significantly higher compared with those in control group (with t values of 5.48, 7.11, and 15.41, respectively, P<0.05). After 24 hours of culture, 51 DEGs with significantly differential expression were detected in high-concentration capsaicin group of cells compared with those in control group ( P<0.05), with 31 upregulated and 20 downregulated genes. GO analysis showed that the significantly upregulated and significantly downregulated DEGs mainly participated in biological processes such as extracellular matrix (ECM) polymerization, extracellular structure organization, collagen metabolic process regulation, and ECM component secretion regulation. KEGG analysis showed that the significantly upregulated and significantly downregulated DEGs mainly participated in cell apoptosis-related pathways such as the phosphatidylinositol 3-kinase/Akt pathway and tumor necrosis factor signaling pathway. After 48 hours of culture, the cell apoptosis rates in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 6.38 and 9.09, respectively, P<0.05). The p-mTOR/mTOR ratio in cells in low-concentration capsaicin group was significantly higher than that in control group ( t=2.74, P<0.05). The p-Akt/Akt and p-mTOR/mTOR ratios in cells in high-concentration capsaicin group were significantly higher than those in control group (with t values of 4.43 and 3.33, respectively, P<0.05). At 12 days after injury, the p-Akt/Akt and p-mTOR/mTOR ratios in wounds of diabetic mice in high-concentration capsaicin group were 0.470±0.044 and 0.549±0.106, respectively, which were significantly higher than 0.189±0.058 and 0.241±0.120 in control group (with t values of 6.67 and 3.36, respectively, P<0.05). Conclusions:Capsaicin can promote the healing of full-thickness skin defect wounds in diabetic mice by activating the Akt/mTOR signaling pathway in fibroblasts, thereby inhibiting apoptosis.

ObjectiveTo identify the rate， population characteristics， and vaccination history of repeat infections among previously infected people in the current epidemic based on the rate of repeat infection and population characteristics of different mutant strains at different times in Pudong New Area of Shanghai， and to provide reference for the prevention and control strategies of novel coronavirus repeat infections. MethodsA total of 9 250 investigated subjects were randomly selected from the new cases of asymptomatic infection and confirmed cases reported by Pudong New Area from March to May 2022. The investigation mainly focused on demographic characteristics， nucleic acid or antigen test results， and symptoms after infection. The repeat infection rates among different populations were compared， and logistic regression was used to analyze the impact of gender， age， and vaccination status on repeat infections. ResultsThe survey sample of 9 250 people had a response rate of 81.85%. There were 4 043 males （53.40%） and 3 528 females （46.60%）， with a median age of 34 years old （P₂₅， P₇₅： 7， 61）. The overall vaccine uptake rate was 59.44% （4 500/7 571）. In December of 2022， there were 563 cases of repeat infection， with an infection rate of 7.44%. The lowest rate of repeat infection was seen in the 3‒ year-old group （2.86%） and the highest rate in the 30‒ year-old group （12.42%）， with significant differences between different age groups. The repeated infection rate for those who had completed their vaccinations was significantly lower （6.57%） compared to those who had not （7.11%）. The age groups of 3‒ years， 70‒79 years， as well as individuals who completed full vaccination and received booster shots were protective factors against repeat infections. ConclusionThe overall rate of reinfection among the infected in Shanghai during the spring of 2022 was low in the outbreak of the Omicron variant， and the rate of reinfection in the 3‒ year-old group was significantly lower than in other age groups. Completing the full course of vaccination significantly reduces the risk of reinfection. Although the reinfection rate is high in individuals who received booster shots， it remains a mitigating factor compared to those who do not receive the vaccine. It is recommended to continue monitoring reinfections in key populations and further strengthen immunization efforts.

The tricuspid valve has been nicknamed the"forgotten valve"and is often neglected by clinicians.However,tricuspid regurgitation is a common clinical heart valve disease.With the continuous development of transcatheter interventional medical device technology,the treatment of tricuspid regurgitation has gradually attracted attention,and more and more companies are developing interventional medical devices for treating this disease.This review will provide an overview of the current research progress on transcatheter therapy for tricuspid regurgitation repair devices at home and abroad,including the design principles,operational steps,clinical outcomes,and the advantages and disadvantages of these devices.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Taking the course of Chinese traditional medicine as an example, this paper discusses the construction and implementation effect of online teaching mode from the following four aspects: online teaching curriculum design, teaching implementation, teaching effect evaluation, and teaching reflection, with a view to providing beneficial reference for the follow-up hybrid teaching and promoting the construction of hybrid first-class courses by summarizing the experience of online teaching.

Objective To investigate the effect of Liangxue Jiedu decoction on intestinal flora in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods The patients who were hospitalized and diagnosed with HBV-ACLF in Beijing Ditan Hospital from October 2018 to October 2019 were enrolled, and healthy individuals were enrolled as HP group. High-throughput sequencing was used to screen for the differences in bacterial diversity and species between HBV-ACLF patients and healthy individuals, and differentially expressed bacteria between the two groups were screened out at the phylum and genus levels. With the help of in vitro simulated fermentation experiment, fecal samples were collected from the patients with HBV-ACLF and were then cultured in the medium containing different concentrations of Liangxue Jiedu decoction (0, 10%, 50%, and 100%) for 24 hours, and the changes in intestinal flora were analyzed and compared between the HBV-ACLF treatment group, the HBV-ACLF non-treatment group, and the HP group at the genus level. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. Results A total of 10 HBV-ACLF patients were enrolled, with 5 in the HBV-ACLF treatment group and 5 in the HBV-ACLF non-treatment group, and there were 15 individuals in the HP group. Compared with the HP group, the HBV-ACLF non-treatment group had significant reductions in the diversity and abundance of intestinal flora. At the phylum level, Bacteroidetes and Firmicutes were mainly observed in the samples of the HP group, while the HBV-ACLF non-treatment group had a significant reduction in Bacteroidetes and significant increases in Fusobacteria , Proteobacteria , and Fibrobacteres. At the genus level, compared with the HP group, the HBV-ACLF non-treatment group had significant reductions in Ruminococcus, Blautia , and Eubacterium and significant increases in Parabacteroides, Lactobacillus, Fusobacterium , and Streptococcus . The in vitro fermentation experiment showed that compared with the HBV-ACLF non-treatment group, the HBV-ACLF treatment group had significant increases in Ruminococcus, Lachnospira, Bacteroides , and Genusgenus and significant reductions in Fusobacterium and Proteobacteria (all P < 0.05). Conclusion Liangxue Jiedu decoction can regulate intestinal flora disturbance, restore the diversity of intestinal flora, increase dominant bacteria, and reduce pathogenic bacteria, which may be one of its important mechanisms of action in the treatment of HBV-ACLF.

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.
Animals ; Bone Regeneration ; Indoles ; Nanoparticles ; Osteogenesis ; Pharmaceutical Preparations ; Polymers ; Rats

Three patients (patient 1, a 27-years-old male with chronic hepatitis C; patient 2, a 71-years-old male with hepatitis C complicated by hepatocellular carcinoma; patient 3, a 60-years-old male with hepatitis C decompensated cirrhosis) were treated with daclatasvir-based regimens and developed drug resistance or treatment failure. Patient 1 and patient 2 received daclatasvir combined with asunaprevir. No resistance variants in the non-structural protein (NS) 5A region of HCV were detected in the 2 patients before treatment. In patient 1, HCV RNA levels were both <15 IU/ml at 4 weeks of treatment and when the drug was stopped at 24 weeks of treatment. Ten days after the drug withdrawal, virological breakthrough occurred and HCV sequence analysis showed variants at 4 sites, including S122G, L31V, Y93H, and C316N. In patient 2, HCV RNA was <15 IU/ml at 8 weeks of treatment and virological breakthrough occurred at 12 weeks of treatment. Both patients were given sofosbuvir/velpatasvir combined with ribavirin for 12 weeks and achieved sustained virologic response (SVR). Patient 3 received sofosbuvir combined with daclatasvir for 24 weeks. His HCV RNA levels were all <15 IU/ml at 4 and 12 weeks of treatment and when the drugs were stopped at 24 weeks of treatment. Virological breakthrough appeared at 12 weeks of drug withdrawal. Sofosbuvir/velpatasvir combined with ribavirin were given for 24 weeks and SVR was achieved.

Three patients (patient 1, a 27-years-old male with chronic hepatitis C; patient 2, a 71-years-old male with hepatitis C complicated by hepatocellular carcinoma; patient 3, a 60-years-old male with hepatitis C decompensated cirrhosis) were treated with daclatasvir-based regimens and developed drug resistance or treatment failure. Patient 1 and patient 2 received daclatasvir combined with asunaprevir. No resistance variants in the non-structural protein (NS) 5A region of HCV were detected in the 2 patients before treatment. In patient 1, HCV RNA levels were both <15 IU/ml at 4 weeks of treatment and when the drug was stopped at 24 weeks of treatment. Ten days after the drug withdrawal, virological breakthrough occurred and HCV sequence analysis showed variants at 4 sites, including S122G, L31V, Y93H, and C316N. In patient 2, HCV RNA was <15 IU/ml at 8 weeks of treatment and virological breakthrough occurred at 12 weeks of treatment. Both patients were given sofosbuvir/velpatasvir combined with ribavirin for 12 weeks and achieved sustained virologic response (SVR). Patient 3 received sofosbuvir combined with daclatasvir for 24 weeks. His HCV RNA levels were all <15 IU/ml at 4 and 12 weeks of treatment and when the drugs were stopped at 24 weeks of treatment. Virological breakthrough appeared at 12 weeks of drug withdrawal. Sofosbuvir/velpatasvir combined with ribavirin were given for 24 weeks and SVR was achieved.