OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Objective To provide a longitudinal evaluation tool based on the frequency of aggressive be-havior for the aggression assessment of schizophrenia patients.Methods The Life History of Aggression was translated and revised to form the Life History of Aggression-Chinese Version(LHA-CV)based on 369 patients diagnosed with schizophrenia in the Chengdu community and compulsory medical insti-tution.The reliability of LHA-CV was analyzed by means of split-half reliability,test-retest reliability and inter-evaluator consistency.The validity was analyzed by item analysis,construct validity and crite-rion validity.Results Item analysis found that LHA-CV had good homogeneity and discriminant validity.Exploratory factor analysis found that the Kaiser-Meyer-Olkin(KMO)test value was 0.80,and the Bartlett's sphericity test χ2=1203.46(P<0.05),and it revealed four factors including non-physical ag-gression,physical aggression,self-directed aggression and antisocial behavior/consequences.The factor loadings for all 11 items were greater than 0.40.Confirmatory factor analysis was performed on the factor model,Chi-square degree of freedom(χ2/df)was 3.61,root mean square error of approxima-tion(RMSEA)was 0.07,goodness-of-fit index(GFI)was 0.92,comparative fit index(CFI)was 0.90,incremental fit index(IFI)was 0.90,and the discriminant validity of each factor was good.The criterion validity test showed the total score of LHA-CV was positively correlated with the aggressive behavior level of MacArthur Community Violence Instrument,the total score of Buss-Perry Aggression Scale,and the score of Antisocial Personality Disorder Subscale of Personality Diagnostic Question-naire-4th Edition Plus(PDQ-4+_ASPD,P<0.05).The Cronbach's α coefficient of non-physical aggres-sion,physical aggression,self-directed aggression,antisocial behavior/consequences and LHA-CV total score were 0.82,0.73,0.74,0.56 and 0.79,respectively.The test-retest reliability,Spearman-Brown split-half reliability and intra-class correlation coefficient of LHA-CV total score were 0.82(P<0.05),0.66 and 0.99,respectively.Conclusion LHA-CV has good reliability and validity,and can be used as an evaluation tool for longitudinally assessing aggressive behavior in schizophrenia patients.

Objective To investigate the efficacy of Fuzheng Hejie Prescription(composed of Scutellariae Radix,Lonicerae Japonicae Flos,Agastachis Herba,Bupleuri Radix,Atractylodis Rhizoma,Glycyrrhizae Radix et Rhizoma,etc.)in the treatment of respiratory viral infections in children and to observe its effect on inflammatory factors and immune function.Methods A total of 203 children with respiratory viral infection of H1N1 virus were randomly divided into 101 cases in the observation group and 102 cases in the control group.Both groups were given the routine treatment for subsiding fever,maintaining water-electrolyte balance,and ensuring enough sleep.And additionally,the control group was given Ribavirin Granules and Ibuprofen Granules,and the observation group was given Fuzheng Hejie Prescription based on the treatment for the control group.The course of treatment covered 7 days.The changes of traditional Chinese medicine(TCM)syndrome scores and the levels of immunological indicators and inflammatory factors in the two groups were observed before and after the treatment.Moreover,the clinical efficacy,symptom resolution time and the incidence of adverse reactions were compared between the two groups of children.Results(1)In the course of the trial,one case fell off in the observation group and 2 cases fell off in the control group,and eventually 100 children in each group were included in the trial.(2)After 7 days of treatment,the total effective rate of the observation group was 93.00%(93/100),and that of the control group was 88.00%(88/100),and the intergroup comparison showed that the therapeutic effect of the observation group was superior to that of the control group,but the difference was not statistically significant(χ2= 1.454,P = 0.228).(3)After treatment,the scores of primary symptoms and secondary symptoms as well as the total TCM syndrome scores in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the time for the resolution of clinical symptoms such as fever,cough,expectoration and sore throat in the observation group was significantly shorter than that in the control group(P＜0.01).(5)After treatment,the levels of immunological indicators of T lymphocyte subset CD3+ and CD4+ in the two groups were increased compared with those before treatment(P＜0.05),and the levels of CD8+ and B cells were decreased compared with those before treatment(P＜0.05).The intergroup comparison showed that the increase in the levels of CD3+ and CD4+ as well as the decrease in the levels of CD8+ and B cells of the observation group was significantly superior to that of the control group(P＜0.01).(6)After treatment,the levels of inflammatory factors of serum amyloid A(SAA),C-reactive protein(CRP),serum tumor necrosis factor alpha(TNF-α),soluble interleukin 2 receptor(SIL-2R),and interleukin 6(IL-6)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels of interleukin 2(IL-2)and interferon γ(IFN-γ)ls were all significantly increased compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum SAA,CRP,TNF-α,SIL-2R,and IL-6 levels and the increase of serum IL-2 and IFN-γ levels in the observation group were significantly superior to those in the control group(P＜0.01).(7)The incidence of adverse reactions in the observation group was 2.00%(2/100),which was significantly lower than that of 8.00%(8/100)in the control group,but the difference was not statistically significant(χ2 = 3.789,P = 0.052).Conclusion Fuzheng Hejie Prescription exerts certain effect in treating children with respiratory viral infection of H1N1 virus,which can effectively decrease children's TCM syndrome scores,regulate the inflammatory response,improve the immune function,accelerate the relief of clinical symptoms and shorten the course of the disease.

Objective To investigate the risk factors of periprosthetic femoral fracture(PFF)after total knee arthroplasty(TKA)in the elderly and to construct a predictive model for the prevention of PFF after clinical operation.Methods The clinical data of 537 elderly patients who underwent TKA in the orthopedic department of the First Affiliated Hospital of Air Medical University from October 2016 to October 2021 were retrospectively analyzed.The occurrence of PFF during the follow-up period was statistically analyzed and the clinical data were collected.Binary Logistic regression was used to analyze the risk factors of PFF after TKA in the elderly,and a predictive model of PFF after TKA in the elderly was constructed based on the risk factors.Receiver operating characteristic(ROC)curve and Hosmer-Lemeshow(H-L)were used to test the discrimination and calibration of prediction model.Results The patients were followed up for 12 to 72 months after discharge,with a median time of 47 months.During the follow-up period,31 patients(5.77%)developed PFF.Age,osteoporosis,Parkinson's disease and anterior femoral notch(AFN)were the risk factors for PFF after TKA in the elderly(P<0.05),and cross fixation of prosthesis and bone cement fixation were the protective factors(P<0.05).The results of H-L test showed that the risk prediction model of PFF after TKA in the elderly had good calibration(P>0.05).ROC curve analysis showed that the risk prediction model of PFF after TKA in the elderly has high discrimination(area under the curve was 0.858,95%CI:0.826 to 0.887),the sensitivity was 83.87%,the specificity was 88.34%.Conclusion The risk of PFF after TKA in the elderly is high,and prevention should be carried out according to the high risk factors.The prediction model constructed based on the high risk factors has good prediction efficiency.

Objective To understand and assess the quality status of national drug sampling inspection in 2022 and the possible risks of drug quality.Methods With the aim of identifying issues and preventing risks,a sampling model of"dispersed sampling,centralized inspection,exploratory research,and comprehensive evaluation"was used to review the historical inspection data of national drug sampling.The overall quality and potential risks of national drug sampling in 2022 were analyzed,with a focus on identifying and examining the main quality problems and risks.Results The average pass rate of the sampling inspection in 2022 was 99.4% .The overall safety situation of China's post-marketing drug quality is stable and manageable,indicating that the drug quality is at a high level.Conclusions By carrying out exploratory studies related to drug safety,authenticity,and efficacy,national sampling plays an important role in comprehensively evaluating the quality status of drugs.It aids in improving the quality control level of drug varieties and industry standards,strengthening quality and safety supervision,combating illegal practices such as adulteration and falsification,and providing public warnings about drug safety.

Objectives:Present study aimed to use quantitative flow ratio based on Murray's law to analyze the risk factors of impaired side branches perfusion without naked eye visible slowing of blood flow in branches after interventional treatment of true bifurcation lesions of the coronary arteries. Methods:A total of 211 patients with non-left main coronary artery true bifurcation coronary artery disease who underwent percutaneous coronary intervention(PCI)in Hunan Provincial People's Hospital from June 2022 to September 2023 were continuously enrolled,with a total of 234 bifurcation lesions.The general clinical indicators,anatomical characteristics of coronary artery bifurcation lesions,branch protection methods,postoperative branch TIMI blood flow and other data were collected,and quantitative flow ratio(μQFR)was measured for postoperative branch blood vessels.Post-PCI μQFR<0.8 was considered as impaired branch perfusion and was included in the postoperative impaired branch perfusion group(n=51,53 branch lesions).Patients with μQFR≥0.8 were included in the postoperative normal branch perfusion group(n=160,181 branch lesions).Multivariate Logistic regression analysis was used to evaluate the effects of various clinical and anatomical factors on branch perfusion after PCI. Results:The post-PCI branch flow grading of all patients was TIMI grade Ⅲ.The postoperative branch μQFR of 53 vessels(22.6％)in the group with impaired postoperative branch perfusion was 0.70±0.10,and 0.93±0.05 in the group with normal postoperative branch perfusion,and the difference between the two groups was statistically significant(P<0.001).Compared with the postoperative group with normal branch perfusion,the postoperative group with impaired branch perfusion was featured with an elevated branch lesion length,branch reference diameter,postoperative branch opening diameter stenosis rate,postoperative branch narrowest lumen diameter stenosis rate,and a lower main branch-to-branch diameter ratio,preoperative branch narrowest lumen diameter stenosis rate,and preoperative main branch μQFR,all of which were statistically significant(all P<0.05).The postoperative branch opening diameter stenosis rate(r=-0.490,P<0.001),postoperative branch narrowest lumen diameter stenosis rate(r=-0.788,P<0.001),preoperative branch narrowest lumen diameter stenosis rate(r=-0.280,P<0.001),branch narrowest lumen diameter(r=-0.469,P<0.001),branch lesion length(r=-0.157,P=0.016)were negatively correlated with postoperative branch μQFR,and branch reference diameter(r=0.173,P=0.008),main branch/side branch diameter ratio(r=0.194,P=0.003),and branch opening diameter(r=0.328,P<0.001)were positively correlated with postoperative branch μQFR,and none of them were significantly correlated with clinical baseline data(all P>0.05).Multifactorial logistic regression analysis showed that following four factors were independent risk factors for impaired branch perfusion:postoperative stenosis of the narrowest branch lumen diameter(OR=1.228,95％CI:1.144-1.318,P<0.001),postoperative stenosis of the branch opening diameter(OR=1.110,95％CI:1.055-1.168,P<0.001),postoperative stenosis of the narrowest lumen diameter of the main branch(OR=1.115,95％CI:1.042-1.192,P=0.001),and length of the branch lesion(OR=1.121,95％CI:1.021-1.231,P=0016). Conclusions:Some of the patients whose branch flow reached TIMI grade Ⅲ after PCI are still faced the risk of hemodynamical impairment and should be functionally evaluated after PCI.The postoperative stenosis rate of the narrowest branch lumen diameter,postoperative stenosis rate of the branch opening diameter,postoperative stenosis rate of the narrowest lumen diameter of the main branch,and branch lesion length are the risk factors of branch perfusion impairment after PCI for coronary bifurcation lesions.

Tripterifordin and neotripterifordin are important ent-kaurane diterpenoids in the Chinese medicinal herb Tripterygium wilfordii, possessing significant anti-HIV(human immunodeficiency virus) activity. On the basis of elucidating the natural biosynthetic pathways of these compounds, heterologous production with microbial cell factories can help to alleviate the reliance on plant resources and provide abundant raw materials for sustainable production. TwKO is the first CYP450 enzyme involved in the biosynthesis of tripterifordin and neotripterifordin. This study aimed to enhance the catalytic activity of TwKO by site-directed mutagenesis to benefit the production of tripterifordin and neotripterifordin in yeast. The AlphaFold DB established based on the AlphaFold 2 was employed to obtain the protein model of TwKO. According to multiple sequence alignments and principles of natural evolution, the key residues influencing the binding of TwKO to the substrate were identified. Subsequently, functional characterization of the mutants were conducted in Saccharomyces cerevisiae. A total of 71 mutants were obtained, among which 11 and 11 mutants had the abilities of enhancing the production of 16α-hydroxy-ent-kaurenol and 16α-hydroxy-ent-kaurenoic acid, respectively. In addition, 10 mutants could increase the proportion of the oxidation product of 16α-hydroxy-ent-kaurenol. In particular, R304 was identified as a key residue affecting the catalytic specificity of TwKO, the mutation of which led to the specific prodiction of 16α-hydroxy-ent-kaurenol. This study was the first to reveal the key residue affecting the catalytic activity of TwKO and obtained the mutants with increased TwKO activity, lay a foundation for the biosynthesis of tripterifordin and neotripterifordin.
Tripterygium/chemistry* ; Mutagenesis, Site-Directed ; Diterpenes, Kaurane/chemistry* ; Plant Proteins/chemistry* ; Cytochrome P-450 Enzyme System/chemistry* ; Saccharomyces cerevisiae/metabolism*

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*

OBJECTIVE: To evaluate toxicity of raw extract of Panax notoginseng (rPN) and decocted extract of PN (dPN) by a toxicological assay using zebrafish larvae, and explore the mechanism by RNA sequencing assay. METHODS: Zebrafish larvae was used to evaluate acute toxicity of PN in two forms: rPN and dPN. Three doses (0.5, 1.5, and 5.0 µ g/mL) of dPN were used to treat zebrafishes for evaluating the developmental toxicity. Behavior abnormalities, body weight, body length and number of vertebral roots were used as specific phenotypic endpoints. RNA sequencing (RNA-seq) assay was applied to clarify the mechanism of acute toxicity, followed by real time PCR (qPCR) for verification. High performance liquid chromatography analysis was performed to determine the chemoprofile of this herb. RESULTS: The acute toxicity result showed that rPN exerted higher acute toxicity than dPN in inducing death of larval zebrafishes (P<0.01). After daily oral intake for 21 days, dPN at doses of 0.5, 1.5 and 5.0 µ g/mL decreased the body weight, body length, and vertebral number of larval zebrafishes, indicating developmental toxicity of dPN. No other adverse outcome was observed during the experimental period. RNA-seq data revealed 38 genes differentially expressed in dPN-treated zebrafishes, of which carboxypeptidase A1 (cpa1) and opioid growth factor receptor-like 2 (ogfrl2) were identified as functional genes in regulating body development of zebrafishes. qPCR data showed that dPN significantly down-regulated the mRNA expressions of cpa1 and ogfrl2 (both P<0.01), verifying cpa1 and ogfrl2 as target genes for dPN. CONCLUSION This report uncovers the developmental toxicity of dPN, suggesting potential risk of its clinical application in children.
Animals ; Zebrafish/genetics* ; Saponins/pharmacology* ; Panax notoginseng/chemistry* ; Larva ; Sequence Analysis, RNA