Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.

BACKGROUND:The appearance of the crescent sign in femoral head necrosis is a"turning point"in the progression of the disease,and repairing and stabilizing the bone-cartilage interface is particularly important in preventing further progression and collapse of the femoral head.Tissue engineering offers potential advantages in the simultaneous repair and integration of the bone-cartilage interface. OBJECTIVE:To review potentially suitable techniques addressing the subchondral separation in femoral head necrosis. METHODS:Relevant articles from January 1970 to April 2023 were searched in PubMed,Web of Science,and China National Knowledge Infrastructure(CNKI)using English search terms"femoral head necrosis,avascular necrosis of femoral head,osteonecrosis of femoral head"and Chinese search terms"femoral head necrosis,subchondral bone,cartilage,integration of cartilage and subchondral bone".A total of 114 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Structural defects,ischemic and hypoxic environment,inflammatory factors,and stress concentration may cause subchondral separation in osteonecrosis of the femoral head.Subchondral bone collapse and failure of hip-preserving surgery may be associated.Integration of tissue engineering scaffolds with the bone-cartilage interface is one potential approach for treating subchondral separation in osteonecrosis of the femoral head.(2)Current literature suggests that multiphase scaffolds,gradient scaffolds,and composite materials have shown improvements in promoting cell adhesion,proliferation,and deposition of bone and cartilage matrix.These advancements aid in the integration of scaffolds with the bone-cartilage interface and have implications for the treatment of subchondral separation in osteonecrosis of the femoral head.(3)Surface modifications of scaffolds can enhance interface integration efficiency,but they have their advantages and disadvantages.Scaffolds providing different environments can induce differentiation of mesenchymal stem cells and facilitate integration between different interfaces.(4)Future scaffolds for subchondral separation in osteonecrosis of the femoral head are expected to be composite materials with gradient and differentiated biomimetic structures.Surface modifications and stem cell loading can promote integration between the bone-cartilage interface and scaffolds for therapeutic purposes,but further experimental verification is still needed.Challenges include synchronizing scaffold degradation rate with repair progress and ensuring stability between different interfaces.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection. Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120 after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05). Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14-28 d)on the immunization potential.

Objective:To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene. Methods:A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c. 548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+ PM2_Supporting+ PP3+ PP4). Conclusion:Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.

Objective:To investigate the effect of tofacitinib,a pan-Janus kinase(JAK)inhibitor,on transforming growth factor-beta 1(TGF-β1)-induced fibroblast to myofibroblast transition(FMT)and to explore its mechanism.To provide a theoretical basis for the clinical treatment of connective tissue disease-related interstitial lung disease(CTD-ILD).Methods:(1)Human fetal lung fibroblast 1(HFL-1)were cultured in vitro,and 6 groups were established:DMSO blank control group,TGF-β1 in-duction group,and TGF-β1 with different concentrations of tofacitinib(0.5,1.0,2.0,5.0 μmol/L)drug intervention experimental groups.CCK-8 was used to measure the cell viability,and wound-healing assay was performed to measure cell migration ability.After 48 h of combined treatment,quantitative real-time PCR(RT-PCR)and Western blotting were used to detect the gene and protein expression levels of α-smooth muscle actin(α-SMA),fibronectin(FN),and collagen type Ⅰ(COL1).(2)RT-PCR and enzyme-linked immunosorbnent assay(ELISA)were used to detect the interleukin-6(IL-6)gene and protein expression changes,respectively.(3)DMSO carrier controls,1.0 μmol/L and 5.0 μmol/L tofacitinib were added to the cell culture media of different groups for pre-incubation for 30 min,and then TGF-β1 was added to treat for 1 h,6 h and 24 h.The phosphorylation levels of Smad2/3 and signal transducer and activator of transcription 3(STAT3)protein were detected by Western blotting.Results:(1)Tofacitinib inhibited the viability and migration ability of HFL-1 cells after TGF-β1 induction.(2)The expression of α-SMA,COL1A1 and FN1 genes of HFL-1 in the TGF-β1-induced groups was signifi-cantly up-regulated compared with the blank control group(P＜0.05).Compared with the TGF-β1 in-duction group,α-SMA expression in the 5.0 μmol/L tofacitinib intervention group was significantly inhi-bited(P＜0.05).Compared with the TGF-β1-induced group,FN1 gene was significantly inhibited in each intervention group at a concentration of 0.5-5.0 μmol/L(P＜0.05).Compared with the TGF-β1-induced group,the COL1A1 gene expression in each intervention group did not change significantly.(3)Western blotting results showed that the protein levels of α-SMA and FN1 in the TGF-β1-induced group were significantly higher than those in the control group(P＜0.05),and there was no significant difference in the expression of COL1A1.Compared with the TGF-β1-induced group,the α-SMA protein level in the intervention groups with different concentrations decreased.And the differences between the TGF-β1-induced group and 2.0 μmol/L or 5.0 μmol/L intervention groups were statistically significant(P＜0.05).Compared with the TGF-β1-induced group,the FN1 protein levels in the intervention groups with different concentrations showed a downward trend,but the difference was not statistically sig-nificant.There was no difference in COL1A1 protein expression between the intervention groups com-pared with the TGF-β1-induced group.(4)After TGF-β1 acted on HFL-1 cells for 48 h,the gene ex-pression of the IL-6 was up-regulated and IL-6 in culture supernatant was increased,the intervention with tofacitinib partly inhibited the TGF-β1-induced IL-6 gene expression and IL-6 in culture supernatant.TGF-β1 induced the increase of Smad2/3 protein phosphorylation in HFL-1 cells for 1 h and 6 h,STAT3 protein phosphorylation increased at 1 h,6 h and 24 h,the pre-intervention with tofacitinib inhibited the TGF-β1-induced Smad2/3 phosphorylation at 6 h and inhibited TGF-β1-induced STAT3 phosphorylation at 1 h,6 h and 24 h.Conclusion:Tofacitinib can inhibit the transformation of HFL-1 cells into myofi-broblasts induced by TGF-β1,and the mechanism may be through inhibiting the classic Smad2/3 path-way as well as the phosphorylation of STAT3 induced by TGF-β1,thereby protecting the disease progres-sion of pulmonary fibrosis.

Osteonecrosis of the femoral head(ONFH)is a common orthopedic disease,and hip preservation surgery has high clinical value in the early stages of ONFH,especially for young and middle-aged patients.However,the repair of ONFH is heterogeneous,leading to inter-individual variations in the efficacy of hip preservation.Currently,the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation,making it difficult to achieve precise repair.Smart responsive materials have good biocompatibility and self-feedback capability.By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems,new possibilities are provided for the precise repair of ONFH.This paper reviews the research progress of smart responsive materials at home and abroad.Based on the response principles of various materials and the repair characteristics of ONFH,the application prospects of various smart responsive materials such as reactive oxygen species-responsive,fluid shear stress-responsive,and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH,providing new ideas for the precise treatment of ONFH.

Objective:To investigate the independent influencing factors of body mass index (BMI) growth risk during breast cancer treatment and establish a predictive model, and validate its predictive efficacy.Methods:A retrospective cohort study was conducted by a convenience sampling method. 306 eligible breast cancer patients underwent follow-up at the Tianjin Medical University Cancer Hospital between January and May 2023 were selected as the modeling group. The BMI changes of the modeling group patients were monitored during the study period. Patients with BMI changed < ± 0.5 kg/m 2 were classified as the stable group, while those with BMI changed ≥ 0.5 kg/m 2 were classified as the growth group. Factor analysis was conducted, and a predictive model was established. The fitting effect was verified by the Hosmer-Lemeshow test, and the receiver operating characteristic (ROC) curve was drawn to verify the model′s predictive ability. 110 eligible breast cancer patients underwent follow-up at the Tianjin Medical University Cancer Hospital between June and August 2023 were selected as the validation group to verify the predictive effect of the model. Results:The age of the modeling group patients was (48.89 ± 7.78) years, BMI was (25.53 ± 1.39) kg/m 2 and the age of the validation group patients was (50.18 ± 7.70) years, BMI was(24.31 ± 0.86) kg/m 2, both groups were female, there were no significant differences between the two groups (all P>0.05). Axillary lymph node dissection ( OR=4.196, 95% CI 3.512-9.158), chemotherapy duration ( OR=2.002, 95% CI 1.001-3.003), premenopausal status ( OR=3.257, 95% CI 1.244-3.733), low health behavior capacity ( OR=5.977, 95% CI 2.878-7.893), and low physical activity ( OR=3.755, 95% CI 1.244-11.733) were identified as independent influencing factors of BMI change during breast cancer treatment (all P<0.05). The predictive model was P=0.915, with the ROC curve area of 0.950, a J-index of 0.785, a sensitivity of 0.971, and a specificity of 0.814. Internal and external validation of the model in the validation group revealed a sensitivity of 0.858, a specificity of 0.887, and an accuracy of 97.3%. Conclusion:The predictive model exhibited excellent performance and can serve as a valuable tool for formulating nursing intervention strategies to maintain the BMI stability of breast cancer patients during treatment.

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.

The distribution of Ixodes and Ana plasma carried by Ixodes ticks in Anhui Province was clarified as reference for prevention and control of anaplasmosis.In total,630 hard ticks were collected from Jinzhai County,Hanshan County,Jing-de County and Chaohu City in Anhui Province from April to August 2023.Ticks were identified by morphological analysis and 16S rRNA sequencing.Nested PCR with Anaplasma species-specific primers were used to detect 16S rRNA of Anaplasma spe-cies carried by ticks.A phylogenetic tree was constructed using MEGA11.0 software.Of the identified ticks,18.8％(18/96)were Rhipicephalus microplus and 81.2％(78/96)were Haemaphysalis longicorni in Jinzhai County of Anhui Province,all were H.longicorni in Hanshan County and Chaohu City,while the main species in Jingde County was R.microplus.The posi-tive rate of Anaplasma carried by H.longicornis was 30.9％(102/330),which included A.bovis at 1.8％(6/330),A.phagocytophilum at 21.8％(72/330)and uncultured Anaplasma species at 7.3％(24/330).R.microplus was positively cor-related to A.bovis(13.6％,18/132).The uncultured Anaplasma species was mainly detected in host-free ticks.A.phagocy-tophilum was detected in 24.4％of parasitic ticks and 15.8％of host-free ticks.The positive rates of host-free and parasitic ticks were 19.9％and 17.8％,respectively.These results show that H.longicornis and R.microplus were the dominant ticks in several counties of Anhui Province.H.longicornis and R.microplus as well as free and parasitic ticks all carried Anaplas-ma.