Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Objective:To investigate the effects and mechanisms of zinc ion-loaded composite hydrogel (hereinafter referred to as the zinc-containing hydrogel) on infected full-thickness skin defect wounds in diabetic mice.Methods:This study was an experimental study. A poly (glycerol sebacate)-co-poly(ethylene glycol)-g-catechol prepolymer/quaternized-chitosan hydrogel (hereinafter referred to as the simple hydrogel) and a solid-state zinc-containing hydrogel with porous and good adhesion by adding zinc ions to the simple hydrogel were prepared. The release rate of zinc ions from the zinc-containing hydrogel after immersion in phosphate buffer solution (PBS) for 14 days was calculated. The concentration of methicillin-resistant Staphylococcus aureus (MRSA) cultured for 2 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was measured. The scavenging ability of the simple hydrogel, zinc-containing hydrogel, and PBS for 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2, 4, 6-trinitrophenyl) hydrazyl (DPPH) was detected using microplate reader to reflect the ability of oxygen free radical removal. The length of vessels formed by human umbilical vein endothelial cells (HUVECs) cultured for 24 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was measured. The cell viability of L929 cells cultured for 24 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was detected using the cell counting kit-8. The mouse red blood cell suspension was divided into blank control group treated with PBS, simple hydrogel group, zinc-containing hydrogel group, and Triton X-100 group treated with corresponding solution. Hemolysis was detected using microplate reader after 2 hours of treatment, and the hemolysis rate was calculated. All experiments had a sample size of 3. Twenty-one C57BL/6J mice aged 6-8 weeks were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back spine and infected with MRSA. Mice were divided into blank control group treated with PBS, simple hydrogel group, and zinc-containing hydrogel group treated with the corresponding hydrogel. Three days after injury, bacterial concentration in the wounds were measured in all groups of mice ( n=4). On day 0 (immediately), 3, 7, and 14 after injury, the wound infection status of mice was generally observed and the wound healing rate was calculated ( n=5). Hematoxylin-eosin staining and Masson staining were used to detect new epithelium and collagen formation in the wounds of mice on day 14 after injury. Immunofluorescence staining was used to detect neovascularization and distribution of M2 macrophages in the wounds of mice. Results:After immersion for 14 days, the release rate of zinc ions of the zinc-containing hydrogel was (70.5±4.6)%. Compared with the zinc-containing hydrogel, the bacterial concentration was significantly increased after 2 hours of culture with PBS and the simple hydrogel ( P<0.05). The DPPH scavenging rate of the zinc-containing hydrogel was significantly higher than that of PBS and the simple hydrogel (with P values all <0.05). The length of vessels formed by HUVECs cultured for 24 hours with the zinc-containing hydrogel was significantly longer than that cultured with PBS ( P<0.05). Compared with PBS and the simple hydrogel, the cell viability of L929 cells cultured for 24 hours with the zinc-containing hydrogel was significantly higher ( P<0.05). After 2 hours of incubation, compared with that in Triton X-100 group, the hemolysis rate of red blood cells in blank control, simple hydrogel, and zinc-containing hydrogel groups was significantly reduced ( P<0.05); and the hemolysis rate of red blood cells in the latter three groups was similar ( P>0.05). On day 3 after injury, the bacterial concentration in the wounds of mice in zinc-containing hydrogel group was significantly lower than that in blank control and simple hydrogel groups (with P values all <0.05). From day 3 to day 14 after injury, the wounds of mice in all the three groups were gradually healing, and on day 14 after injury, the wounds of mice in the zinc-containing hydrogel group were basically healed. On day 7 after injury, the wound healing rate of mice in zinc-containing hydrogel group was (72.4±8.4)%, which was significantly higher than that of blank control and simple hydrogel groups, being (31.6±6.7)% and (44.7±5.4)%, respectively(with P values all< 0.05). On day 14 after injury, the wound healing rate of mice in zinc-containing hydrogel group was (92.7±4.3)%, which was significantly higher than (73.5±7.4)% in blank control group ( P<0.05). On day 14 after injury, compared with that in blank control and simple hydrogel groups, the newly formed epidermis in mice wound of zinc-containing hydrogel group was longer and thicker, with more collagen deposition, and a more abundant distribution of new vessels and M2 macrophages. Conclusions:The zinc-containing hydrogel exhibits good biocompatibility, oxygen free radical scavenging capacity, and antimicrobial effects both in vitro and in vivo, as well as angiogenic promotion capability. It can provide sustained release of zinc ions to promote re-epithelialization and collagen synthesis, thus enhancing the healing of infected full-thickness skin defect wounds in diabetic mice.

Objective:To evaluate the safety and efficacy of the domestic robotic surgical system for general surgery.Methods:A prospective single-center, single-arm exploratory study was conducted at Gansu Provincial People's Hospital from Jun 2022 to Oct 2023, enrolling 54 patients undergoing general surgery using domestically produced Toumai? Endoscopic Surgical Robotic System. The primary study endpoint was surgical success rate, and the secondary study endpoints were intraoperative bleeding, operative time, complications, system performance, hospitalization days.Results:In this study, robotic surgery was successfully completed in 52 patients, and in 2 patients undergoing thyroid operation it was converted to open surgery due to bleeding, with a success rate of 96%, no organ injury or death during surgery, and no system failure. The types of surgery included cholecystectomy, radical gastric cancer resection, radical colorectal cancer resection, inguinal hernia repair, partial hepatectomy, total thyroidectomy and choledocho-jejunal anastomosis.Conclusion:The study provides preliminary evidence of the safety and efficacy of the Toumai? Endoscopic Surgical Robotic System for the treatment of general surgical diseases.

Objective To understand the occurrence of catheter-associated urinary tract infection(CAUTI)in pa-tients with catheterization,and provide evidence for reducing the incidence of CAUTI.Methods Based on monito-ring requirement for CAUTI in competency building project of healthcare-associated infection(HAI)prevention and control established by Hospital Infection Management Committee of Chinese Hospital Association,CAUTI among patients who hospitalized and received urinary catheterization ≥2 days in a hospital from January to December 2014 were analyzed prospectively,incidences of CAUTI in different patients were compared.Results A total of 6 046 patients with urinary catheterization were monitored,166 of whom developed CAUTI,incidence of CAUTI was 2.75%,the total urinary catheter days were 31 833 days,incidence of CAUTI was 5.21 per 1 000 urinary catheter days.There was no significant difference in the incidence of CAUTI among patients of different genders (χ2 =1 .23, P =0.54);incidence of CAUTI in patients > 60 years old was higher than those ≤60 years (4.72% vs 2.07%,χ2=30.38,P <0.01);incidence of CAUTI in patients with different duration of catheterization was significantly dif-ferent(χ2 = 251 .14,P <0.01 );with the prolongation of duration of catheterization,incidence of CAUTI also in-creased(trendχ2 =211 .82,P <0.001 ).Patients in department of neurology had the longest average catheterization time(14.84 days)and highest incidence of CAUTI(15.00%,10.11 ‰);patients in the other departments of surgery had the shortest average catheterization time(3.56 days)and lowest incidence of CAUTI(0.97%,2.74‰);inci-dences of CAUTI in patients with urinary catheterization in different departments were significantly different(χ2 =302.24,P <0.001).166 CAUTI patients were isolated 66 isolates of pathogenic strains,86.36% were gram-nega-tive bacilli,33.33% of which were Escherichia coli .Conclusion CAUTI is related to the age of patients and dura-tion of indwelling urinary catheter.Daily assessment on the necessity of indwelling catheter and timely removal of catheter is helpful for reducing the occurrence of CAUTI.

Objective To explore the telomere length (TL) in buccal cells and its possible implications for long-lived families of Zhuang nationality in Bama area of Guangxi.Methods Relative TL in buccal cells from Bama long-lived families (BLF,n=1250) was determined by real time PCR and compared between Bama non-long-lived families (BNLF,n=556) and Pingguo longlived families (PLF,n=630).All participants were Zhuang ethnic.Results The TL in buccal cells was negatively correlated with age (R=-0.215,P=0.000) and was independent of sex in all subjects (n=2436).There were no significant differences in TL between males and females in different of ages in BLF (all P＞0.05).Similar tendency was observed in most but not all age groups in the two other families.The TL was significantly longer in BLF aged over 65 years (the first offspring of the longlived individual) than in BNLF aged over 65 years (1.969 vs.1.622,P=0.004) and the TL of BLF aged over 90 years was comparable to that of BNLF aged over 65 years (1.662 vs.1.622,P=0.955),which indicating that the offspring of long-lived individuals inherited longer TL from their parental generation.Conclusions Telomere length is shorten with aging in long-lived families in Bama area.The TL of BLF has a tendency of inheritance,which may be one of the mechanisms of longevity in Bama area.

Under the general requirements of China's national health reform, the basic framework of Shanghai's health reform was constructed at five different aspects the long term vision, goal, strategies, measures, supportive reform activities. The general thought of Shanghai's health reform can be concluded into two aspects: first, establishing a basic healthcare system of covering both urban and rural residents universally; second, enhancing the foundation of enabling sustainable health development.