Objective To analyze trend changes of disease burden of hypertensive nephropathy (HTN) between 2012 and 2023 in Chongqing, and to provide the suggestion for HTN prevention and treatment. Methods Death cases of HTN from Chongqing death registration data between 2012 and 2023 were analyzed to calculate indicators such as mortality, age standardization mortality rate (ASMR), rate of years of life lost (YLL) and Average years of life lost. The mortality of HTN between male and female, urban and rural were compared by Chi-square test. The trend change was explained by average annual percent of change (AAPC). Results The mortality and standardized mortality of HTN in Chongqing decreased from 5.44/100 000 and 3.13/100 000 in 2012 to 2.76/100 000 and 1.07/100,000 in 2023 respectively. The average annual percent change (AAPC) was -5.41% and -8.35% respectively, and the differences in the change trends were statistically significant (P<0.01). The mortality and standardized mortality of HTN in males and females decreased with AAPC of 5.50%, 8.07%, 5.27% and 8.69% respectively, and the differences in the change trends were all statistically significant (all P< 0.05). From 2012 to 2014, 2019 and 2021, the mortality rate of HTN in rural areas was higher than that in urban areas (all P < 0.05). The mortality and standardized mortality of HTN in rural areas decreased with AAPC of 6.58% and 9.46% respectively, and the differences in the change trends were all statistically significant (all P<0.05). The rate of YLL and standardized YLL of HTN in Chongqing decreased from 96.02/100 000 and 60.42/100 000 in 2012 to 44.98/100 000 and 21.49/100 000 in 2023 respectively. The AAPC was -5.83% and -7.80% respectively, and the differences in the change trends were statistically significant (both P < 0.05). AYLL of HTN were 17.88 years in 2012, and it was 17.08 years in 2023. There were no statistically significant differences in the changes (both P > 0.05). The standardized AYLL of HTN in rural areas increased at an average annual rate of 1.14%, and the difference was statistically significant (P < 0.05). Conclusion The mortality and YLL rate of HNT in Chongqing was lower than it in China. Moreover, its trend was decreased. It should be strengthened early screening and healthy management of HNT.

OBJECTIVE: It has been reported that the mRNA expression of serine protease 23 (PRSS23) was increased in skin fibroblasts from systemic sclerosis patients (SSc). The purpose of this study is to explore the pathogenetic effect and mechanism of PRSS23 in skin fibrosis of SSc. METHODS: The expression of PRSS23 in skin tissues from the SSc patients and healthy controls was detected by immunohisto-chemistry. Fibroblasts isolated from fresh skin tissue were used to detect the expression of PRSS23 by real-time quantitative PCR (RT-qPCR) and Western blot. Overexprssion of PRSS23 in BJ, the fibroblasts cell line of skin, was constructed by lentivirus. After stimulation with 400 μmol/L hydrogen peroxide for 12 h, Annexin V/7-AAD staining was used to detect apoptosis of fibroblasts; flow cytometry and Western blot were used to detect the expression of apoptosis-related protein cleaved Caspase-3. The expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in fibroblasts was detected by RT-qPCR and enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the healthy controls, the expression of PRSS23 in skin tissues of the SSc patients was significantly increased [4.952 (3.806-5.439) vs. 0.806 (0.395-1.173), P < 0.001], and fibroblast was the main cell that expressed PRSS23. The mRNA [27.59 (25.02-30.00) vs. 1.00, P < 0.001] and protein [0.675 (0.587-0.837) vs. 0.451 (0.342-0.502), P=0.029] of PRSS23 in skin fibroblasts isolated from the SSc patients were significantly up-regulated. Compared with the control group, the anti-apoptotic ability of skin fibroblasts overexpressing PRSS23 was enhanced, and the proportion of apoptotic cells was significantly reduced after hydrogen peroxide induction [(5.043±1.097)% vs. (17.480±3.212)%, P=0.022], the expression of apoptosis-related protein cleaved Caspase-3 was also markedly reduced [(0.718±0.022) vs. (1.422±0.105), P=0.003]. In addition, the mRNA [(99.780±1.796) vs. (1.000±0.004), P < 0.001] and protein [(211.600±2.431) ng/L vs. (65.930±1.768) ng/L, P < 0.001] of IL-6 in the fibroblasts overexpressing PRSS23 were significantly up-regulated; the mRNA[(3.555±0.555) vs. (1.000±0.004), P < 0.001] and protein levels [(41.190±0.949) ng/L vs. (31.150±0.360) ng/L, P < 0.001] of TNF-α in the fibroblasts overexpressing PRSS23 were also significantly up-regulated. CONCLUSION The expression of PRSS23 is increased in skin fibroblasts of SSc patients. PRSS23 can inhibit cell apoptosis, promote the secretion of inflammatory factors such as IL-6 and TNF-α, and regulate the process that skin fibroblasts transform into pro-inflammatory type. So, PRSS23 is associated with the development of skin fibrosis.
Humans ; Scleroderma, Systemic/enzymology* ; Fibroblasts/pathology* ; Apoptosis ; Skin/metabolism* ; Fibrosis ; Interleukin-6/metabolism* ; Caspase 3/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Male ; Female ; Cells, Cultured ; RNA, Messenger/metabolism* ; Middle Aged ; Adult ; Serine Endopeptidases/genetics*

Objective To observe the effect of sirtuin 1(SIRT1)on rat myocardial fibrosis induced by pressure overload and the proliferation of cardiac fibroblasts induced by angiotensin Ⅱ(Ang Ⅱ),and to explore the molecular mechanisms.Methods The pressure overload-induced myocardial fibrosis was established by abdominal aorta constriction(AAC)procedure in vi-vo.After treatment with SIRT1 activator,the myocardial interstitial fibrosis and the collagen volume fraction were evaluated by Masson's trichrome staining.The protein expressions of TGF-β1/Smads were determined by immunohistochemical analy-sis.After in vitro intervention of Ang Ⅱ or Ang Ⅱ with SIRT1 activator,the fibroblasts proliferation was detected by MTT as-say.The mRNA and protein expressions of collagen Ⅰ/Ⅲ(Col1α1/3α1),SIRT1 and TGF-β1/Smads in myocardial tissue and fi-broblasts were evaluated by qRT-PCR and Western blotting.Results Compared with the sham operation group,myocardial in-terstitial fibrosis was significantly observed in the pressure overload model group,myocardial collagen volume fraction was in-creased,expressions of Col1α1/3α1 and TGF-β1/Smads were significantly increased,and SIRT1 expression was decreased.After the intervention of SRT1720,SIRT1 activator could improve the myocardial interstitial fibrosis induced by pressure overload,downregulate the expressions of Col1α1/3α1 and TGF-β1/Smads,and upregulate the expression of SIRT1.Meanwhile,correla-tion analysis showed that the protein expression of SIRT1 was negatively correlated with the expression of TGF-β1.In addition,SRT1720 also inhibited Ang Ⅱ-induced fibroblast proliferation and increased expression of Col1α1/3α1 and TGF-β1.Conclusion Activation of SIRT1 inhibits pressure overload-induced myocardial fibrosis and Ang Ⅱ-induced fibroblasts proliferation via regu-lation of the TGF-β1/Smads signaling pathway.

The c-ros oncogene 1(ROS1)gene is primarily fused with CD74 and SLC34A in non-small cell lung cancer(NSCLC),and also fused with SDC4,EZR,TPM3,TFG,ZCCHC8,SLMAP,and MYO5C genes.The ROS1 fusion genes retain the tyrosine kinase structural domain of ROS1.When abnormally activated,the ROS1 fusion genes can activate the ROS1 tyro-sine kinase domain and downstream signaling pathways,leading to tumor growth,proliferation,migration,and invasion.Patients with ROS1 fusion-positive NSCLC are characterized by a young age of onset and a likelihood of brain metastasis.The first drug approved in China for ROS1 fusion-positive NSCLC is crizotinib,a ROS1 tyrosine kinase inhibitor.However,crizotinib is prone to developing resistance.Understanding its resistance mechanisms and how to treat ROS1-positive NSCLC after resistance has become an urgent issue that must be addressed.Highly effective and safe multi-targeted drugs bring hope to patients with ROS1-positive NSCLC.This article reviews the multi-targeted drugs for ROS1 gene-positive NSCLC and their resistance mecha-nisms.

Objective:To understand the current status of human resources in Operating Room nursing in China, so as to provide reference for nursing management, human resource allocation, nursing education and training in Operating Rooms.Methods:Using the stratified sampling method, a self-made Operating Room nursing human resource survey questionnaire of Chinese Nursing Society was used as a research tool in July 2021 to investigate the general situation, surgical workload, human resource allocation, Operating Room management, Operating Room information construction, nursing education and training of 2 201 hospitals in 31 provinces, autonomous regions and municipalities of China.Results:Among the 2 201 hospitals, there were 1 021 tertiary hospitals (46.39%), 1 177 secondary hospitals (50.75%), and 63 primary and below hospitals (2.86%). There were 2 056 hospitals with less than 30 Operating Rooms, accounting for 93.41%. There were 1 991 hospitals with an annual number of surgical cases less than 20 000, accounting for 90.46%, the educational background of Operating Room nurses was mainly undergraduate (66.93%, 43 359/64 780), with a total of 67.99% (44 045/64 780) having a bachelor's degree or above. Nurses were the main professional titles (42.66%, 27 632/64 780). Number of Operating Rooms: the number of Operating Room nurses (median) was 1: 2.43 and 78.96% (1 738/2 201) of hospital operating theatres were managed by Nursing Departments or hospitals. A total of 1 479 hospitals (67.20%) established anesthesia recovery rooms in their Operating Rooms, which was higher than 59.34% (1 210 hospitals) surveyed in 2016, and the difference was statistically significant (χ 2=226.701, P<0.01). 74.69% (1 644/2 201) and 87.87% (1 934/2 201) of hospitals carried out post management and capacity classification management in Operating Rooms, respectively. Day surgery and robotic surgery were performed in 47.80% (1 052/201) and 7.68% (169/2 201) hospitals, respectively. 36.98% (814/2 201) of the hospitals passed the information evaluation system certification and 64.61% (1 422/2 201) of the hospitals used the Operating Room information management system. In the Operating Room information system of the hospital, 2.54% (56/2 201) had intelligent functions. And 77.24% (1 700/2 201) of hospitals participated in the qualification training of Operating Room specialist nurses. Conclusions:By July 2021, the number of Operating Rooms in most hospitals in China is less than 30, and the annual number of operating cases is less than 20 000. The educational background and professional title of Operating Room nurses are mainly undergraduate and nurse. More than 60% of hospitals have set up anesthesia recovery rooms and have information management systems for Operating Rooms. At the same time, Operating Rooms in Chinese hospitals have widely implemented diversified nursing management models such as post management and ability grading management.

Objective To investigate the causes of a cluster of suspected neonatal carbapenem-resistant Klebsiella pneumoniae(CRKP)bloodstream infection(BSI)in the neonatal department of a hospital,and provide references for the effective control of the occurrence of healthcare-associated infection(HAI).Methods Epidemiological in-vestigation on 3 neonates with CRKP BSI in the neonatal department from January 31 to February 6,2023 was per-formed.Specimens from environmental object surfaces were taken for environmental hygiene monitoring,and effec-tive control measures were taken according to the risk factors.Results From January 31 to February 6,2023,a to-tal of 60 neonates were admitted in the neonatal department,including 16 with peripherally inserted central venous catheter(PICC).Three neonates had CRKP BSI,with a incidence of 5.00％.There were 33 hospitalized neonates on the day(February 7)when the cluster of HAI was reported,with a prevalence rate of 9.09％(3/33).CRKP BSI rate in the neonatal department of this hospital from January 31 to February 6,2023 was higher than that in 2022(P＜0.001).The incubators of the 3 neonates with CRKP BSI were in the same ward and adjacent to each other.The first neonate with CRKP BSI(who developed BSI on January 31)underwent PICC maintenance on Feb-ruary 4,and the other 2 neonates with PICC maintenance immediately following the first one also developed CRKP BSI.CRKP were isolated from blood culture of all 3 neonates,and antimicrobial susceptibility testing results were consistent.Conclusion The occurrence of the cluster event of neonatal CRKP BSI may be related to the failure of strict implementation of aseptic procedures during PICC maintenance and cross contamination among items.

Objective:To analyze the clinical phenotype and gene mutation of a genetic coagulation factor Ⅻ(FⅫ)deficiency pedigree and explore the molecular pathogenesis.Methods:The activated partial thromboplastin time(APTT)and FⅫ activity(FⅫ:C)were detected by clotting method.The FⅫ antigen(FⅫ:Ag)was tested with ELISA.All exons and flanks of F12 gene were determined by Sanger sequencing.ClustalX-2.1-win,PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site,forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.Results:The APTT of the proband prolonged to 71.3 s.The FⅫ:C and FⅫ;Ag were decreased to 5％and 6％,respectively.There were two heterozygous missense mutations c.580G＞T and c.1681G＞A detected in exon 7 and exon 14 of F12 gene,resultingin p.Gly175Cys and p.Gly542Ser,severally.Proband's father carried the p.Gly175Cys heterozygous mutation,while mother,brother and daughter had the p.Gly542Ser heterozygous mutation.Software analysis showed that both Gly175 and Gly542 were conserved,the two mutations were harmful and when mutations had occurred,the corresponding sites affected the protein local structure.Conclusion:The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FⅫ deficiency pedigree.The p.Gly175Cys mutation has been detected for the first time in the world.

ObjectiveTo investigate the effect of chorionicity， gestational age at birth and birth weight discordance on neonatal outcomes in twin pregnancies. MethodsWe conducted a population-based retrospective study of monochorionic diamniotic （MCDA） twin pregnancies and dichorionic diamniotic （DCDA） twin pregnancies who were admitted in the First Affiliated Hospital， Sun Yat-sen University from January 2015 to December 2020. A total of 1504 live-born twins were included， with 386 cases in MCDA group and 1118 cases in DCDA groups， respectively. The comparison of neonatal outcomes between MCDA and DCDA twins was performed using t-test， Wilcoxon rank sum test， Chi-square test or Fisher’s exact test. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight discordance and sex on neonatal outcomes. There were 168 live-born twins affected by inter-twin birth weight discordance≥25%， with 96 cases in MCDA group and 72 cases in DCDA groups， respectively. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight light or heavy （small twin or large twin） of the twin and sex on neonatal outcomes. ResultsAmong the 1 504 newborns， gestational age at birth was lower in MCDA group compared with DCDA group （P = 0.000）， and the degree of birth weight discordance was higher in MCDA group than that of the DCDA group （P = 0.001）. Birth asphyxia， respiratory distress syndrome （RDS）， bronchopulmonary dysplasia （BPD）， and sepsis were more frequency in MCDA group compared with DCDA group （P = 0.000， P = 0.000， P = 0.000， P = 0.000）. Low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis， necrotizing enterocolitis （NEC）≥stageⅡ， acute kidney injury （AKI）， retinopathy of prematurity （ROP）， and neonatal death respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.011， P = 0.000， P = 0.000， P = 0.000）. High degree of birth weight discordance was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP respectively （P = 0.045， P = 0.000， P = 0.000， P = 0.004， P = 0.017 ）. Chorionicity was not an independent risk factor for neonatal morbidity and death （P > 0.05）. Among the 168 twins with birth weight discordance ≥25%， low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP， respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.000）； small twin was an independent risk factor for birth asphyxia and BPD， respectively （ P = 0.013， P = 0.001）； chorionicity was not an independent risk factor for neonatal morbidity （P > 0.05）. ConclusionChorionicity was not an independent risk factor for adverse neonatal outcome in twin births. Low gestational age at birth and high degree of birth weight discordance were independent risk factor for adverse neonatal outcome in twin births. Small twins had increased risk of adverse neonatal outcome in twins with birth weight discordance ≥25%.

Objective To investigate the effects and mechanisms of TAR DNA-binding protein 43(TDP-43)on oxygen-glucose deprivation(OGD)-induced apoptosis in mouse atrial myocytes(HL-1 cells).Methods The in vitro cultured mouse atrial myocytes(HL-1 cells)were divided into:(1)control group and groups with different OGD treatment times(2,4,8,16 h),and cell viability was detected by CCK-8 assay,and TDP-43 protein expression level was detected by Western blotting,which was used to determine the time point of OGD induction for the subsequent study;(2)control and OGD groups,flow cytometry was used to detect apoptosis,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect adenosine triphosphate(ATP)relative content,microplate method to detect malondialdehyde(MDA)content,and WST-1 method to detect superoxide dismutase(SOD)content.Mouse atrial myocytes(HL-1 cells)transfected with lentivirus were divided into:(1)negative control lentiviral intervention group(NC-shRNA),TDP-43 knockdown lentiviral intervention group(TDP-43-shRNA1,TDP-43-shRNA2,TDP-43-shRNA3),and Western blotting was used to detect the TDP-43 protein expression level,and the group with the highest lentiviral knockdown efficiency was selected as the TDP-43-shRNA for subsequent experiments;(2)NC-shRNA group,TDP-43-shRNA group,OGD+NC-shRNA group,OGD+TDP-43-shRNA group,under normoxic and OGD conditions,flow cytometry was used to detect the apoptosis rate,MitoTracker staining to detect mitochondrial morphology,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect the relative content of ATP,flow cytometry to detect the fluorescence intensity of reactive oxygen species(ROS),microplate to detect the content of MDA,and WST-1 to detect the content of SOD.Results CCK-8 method showed that,with the prolongation of OGD time,the viability of mouse atrial myocytes(HL-1 cells)gradually decreased;Western blotting assay showed that the expression level of TDP-43 protein gradually increased,and both of them showed a strong time-dependence.Compared with control group,mouse atrial myocytes(HL-1 cells)viability was the lowest(P<0.05)and TDP-43 protein expression was the highest(P<0.05)at 16 h of OGD,accordingly,OGD 16 h was chosen as the induction time point for subsequent experiments.Compared with control group,the apoptosis rate,the fluorescence intensity ratio of mitochondrial membrane potential and the content of MDA increased,the relative content of ATP and SOD decreased in OGD group,and the differences were all statistically significant(P<0.05).Western blotting detection showed that compared with NC-shRNA group,the TDP-43-shRNA2 group had the most obvious reduction in TDP-43 protein expression level(P<0.05)and the highest knockdown efficiency,so the TDP-43-shRNA2 group was selected for subsequent experiments.The results of flow cytometry showed that under normoxic conditions,there was no significant change in the apoptosis rate in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);and under OGD conditions,the apoptosis rate in OGD+TDP-43-shRNA group reduced when compared with OGD+NC-shRNA group(P<0.05).MitoTracker staining results showed that the mitochondrial morphology of TDP-43-shRNA group was intact without significant changes compared with NC-shRNA group;the mitochondria of OGD+NC-shRNA group increased in number,most of which were fragmented and scattered in distribution;compared with OGD+NC-shRNA group,the mitochondrial morphology of OGD+TDP-43-shRNA group was restored.Under normoxic conditions,there were no significant changes in mitochondrial membrane potential,relative ATP content,ROS fluorescence intensity,MDA content,and SOD content in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);however,under OGD conditions,the ratio of fluorescence intensity of mitochondrial membrane potential of cells the fluorescence intensity of ROS,and the content of MDA decreased,and the relative content of ATP and the content of SOD increased in OGD+TDP-43-shRNA group compared with that of OGD+NC-shRNA group,and all of these differences was statistically significant(P<0.05).Conclusion TDP-43 exacerbates OGD-induced mitochondrial dysfunction by regulating cardiomyocyte apoptosis;therefore,knockdown of TDP-43 expression is expected to be a potential therapeutic strategy for ischemic cardiomyopathy.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.