BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

Objective: To analyze the epidemiological characteristics and incidence trends of pulmonary tuberculosis (TB) in children aged 0-14 years in Shaanxi Province from 2010 to 2024, so as to provide a reference for optimizing child TB prevention and control strategies. Methods: Data on pulmonary TB cases in children aged 0-14 years and demographic information in Shaanxi Province from 2010 to 2024 were collected from Surveillance and Reporting Management System with Disease Prevention and Control Information Management System under the National Health Security Informatization Project Disease Prevention and Control Information System. A Joinpoint regression model was established to analyze the temporal, spatial, and population distribution trends of child pulmonary TB incidence. Results: A total of 2 954 cases of pulmonary TB in children aged 0-14 years were reported in Shaanxi Province from 2010 to 2024, accounting for 0.97% of all TB cases in the general population. The average annual reported incidence rate in children was 3.32 per 100 000. Among these cases, 804 were pathogenetically positive, showing a increasing trend ( χ 2 trend =420.94, P < 0.01 ). The overall reported incidence rate of pulmonary TB in children aged 0-14 years in Shaanxi Province showed a decreasing trend, dropping from 5.35 per 100 000 in 2010 to 2.41 per 100 000 in 2024. Joinpoint regression analysis identified three distinct phases for the reported incidence rate of TB:a rapid decline from 2010 to 2013 (APC=-20.02%, 95% CI = -33.64% to -10.42%), a slight increase from 2013 to 2017 (APC=11.18%, 95% CI =3.07%-24.17%) and a slight decline again from 2017 to 2024 (APC= -7.27 %, 95% CI =-12.73% to -4.30%) (all P <0.01). Among children aged 0-14 years, the age group with the highest average annual reported incidence rate was 10-14 years (8.02 per 100 000), followed by 5-9 years (1.44 per 100 000), and 0-4 years had the lowest rate (0.95 per 100 000). The difference in reported incidence rates among the three age groups was statistically significant ( χ 2= 51.91, P <0.01). The average annual reported incidence rate of TB was 3.25 per 100 000 in boys and 3.39 per 100 000 in girls, with no statistically significant difference ( χ 2=2.01, P >0.05). There was no obvious periodic variation in the annual case reporting. Among all cities in Shaanxi Province, Ankang City had the highest average annual reported incidence rate (5.16 per 100 000). Conclusions From 2010 to 2024, the reported incidence rate of pulmonary TB in children aged 0-14 years in Shaanxi Province showed an overall decreasing trend. However, it is still necessary to strengthen active surveillance, implement targeted measures in high incidence areas such as Ankang City, and maintain continuous attention to child TB prevention and control.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

Objective To evaluate five types of DIC scoring systems based on sepsis patients,to explore the values of different DIC scoring systems in the occurrence and prognosis of DIC in sepsis patients,and to compare the applicability of different DIC scoring systems for sepsis complicated with DIC.Methods Laboratory indexes and clinical data from sepsis patients who had been hospitalized in Gansu Provincial People's Hospital from December 1,2019 to December 31,2021 were retrospectively analyzed within 24 hours.Five types of DIC scoring systems were used to score,and the difference of diagnostic rate and discharge outcome in sepsis patients with different severity was compared.The ROC curves of five DIC scoring systems were established to evaluate the accu-racy of DIC in sepsis patients.Results The fatality rate of sepsis increased with the severity of sepsis(P<0.05).There were statistically significant differences in discharge outcomes between DIC and non-DIC in the five scoring systems(P<0.05).JMHW,CDSS and part of ISTH were detected in JAAM cases,while ISTH was detected in non-dominant ISTH cases.ISTH,JAAM,JMHW,CDSS,and non-dominant ISTH5 scoring systems were used to diagnose DIC,and absence of full health restoration and death were 3.0,3.8,4.2,3.9,and 3.0 times higher than non-DIC cases,respectively.Conclusion JAAM scoring system has higher diagnostic rate and sensitivity for adult sepsis.CDSS and JMHW scoring systems are more accurate in predicting the prognosis of sepsis patients.

Objective To investigate the effects of Zhoufei Pingchuan Capsules on the balance of peripheral blood helper T lymphocyte 17 cell/regulatory T lymphocyte cell(Th17/Treg)and related inflammatory factors in peripheral blood of patients with stable chronic obstructive pulmonary disease(COPD)with lung-kidney qi deficiency syndrome.Methods Totally 40 COPD patients were randomly divided into the study group and the control group,with 20 cases in each group.Another 20 cases were in the healthy group.The control group was given tiotropium bromide powder inhalation,18 μg/time,1 time/d,inhalation;on the basis of the control group,the study group was given Zhoufei Pingchuan Capsules,3 pills/time,3 times/d,orally.All patients were treated for 8 weeks.The healthy group was not given any intervention.Forced expiratory volume in one second(FEV1),FEV1/forced vital capacity(FEV1/FVC),maximum mid-expiratory flow(MMEF),carbon monoxide diffusing capacity/alveolar ventilation(DLCO/VA),arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),COPD assessment test(CAT)score,Th17/Treg ratio,cytokines interleukin(IL)-17,IL-22,IL-10,and transforming growth factor-β1(TGF-β1)were compared before and after treatment.Results Compared with before treatment,the lung function indexes(FEV1,FEV1/FVC,MMEF,DLCO/VA),blood gas indexes(PaO2,PaCO2)and CAT score in the study group after treatment were significantly improved(P<0.05).After treatment,the mean values of MMEF,DLCO/VA,PaCO2 and CAT score in the study group were better than those in the control group(P<0.05).Compared with before treatment,the levels of Th17,IL-17 and IL-22 in the study group were significantly lower,and the levels of Treg,IL-10 and TGF-β1 were significantly higher(P<0.05).After treatment,there were significant differences in Th17,Treg,IL-17,IL-22,IL-10 and TGF-β1 among the three groups(P<0.01).Further pairwise comparison showed that Th17 ranked in the order of high and low was control group>study group>healthy group,Treg in the order of high and low was healthy group>study group>control group,the levels of IL-17 and IL-22 in the order of high and low were control group>study group>healthy group,and the levels of IL-10 and TGF-β1 in the order of high and low were healthy group>study group>control group,with statistical significance(P<0.05).Conclusion Zhoufei Pingchuan Capsules can improve the lung function,arterial blood gas and symptom score of patients with lung-kidney qi deficiency syndrome in stable stage of COPD.Its mechanism may be related to regulating the balance of Th17/Treg,down-regulating the levels of Th17,IL-17 and IL-22,and up-regulating the levels of Treg,IL-10 and TGF-β1,in order to reduce airway inflammation and regulate immune homeostasis.

Currently, the management of domestic laboratory developed test (LDT) is still in the exploration stage, and new plans and ideas need to be investigated that are suitable for our national development. By analyzing encountered issues, combining the actual needs of the government, healthcare reform, and patients, this article proposes that "promoting healthy development of LDT projects and focusing on the organic combination of patients′ interest protection and innovation support" is an important direction for LDT management, around which the new idea for LDT project management is proposed, that is, LDT management model targeting product registration. The core of this management model is to target product registration and to ensure low service fees for patients and continuous real-time data monitoring. Benefit and risk analysis demonstrate that this management model can to a larger extent balance the realistic demands of patients, medical institutions, in vitro diagnostics companies, and government management departments, which benefits promoting the perfection and development of LDT projects in our country.

According to the relevant requirements of the Chinese Pharmacopoeia and relevant reports, this article briefly introduces the basic principles, research ideas, and precautions for the revision of the “characteristics” standards of Chinese medicinal materials and decoction pieces. In recent years, enterprises and social media reported that the characteristics of Chinese medicinal materials in the market did not fully comply with the characteristics specified in the Chinese Pharmacopoeia. Therefore, this article explored the variation in the characteristics of Chinese medicinal materials and decoction pieces and its main reasons, scientific and reasonable revision of the “characteristics” of Chinese medicinal materials and decoction pieces, the new methods for identifying properties, as well as the issues that need to be noted in revising the characteristics of Chinese medicinal materials and decoction pieces, which provided reference for the revision of the “characteristics” standards of Chinese medicinal materials and decoction pieces.

Objective To investigate the geographical distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Henan Province in 2023, so as to provide insights into the prevention and control of visceral leishmaniasis vectors. Methods A total of 23 counties (districts) were sampled from 18 cities of Henan Province from May to September, 2023 as sandfly surveillance sites, and sandflies were captured using human capture and light trapping methods. Following morphological identification, the changes in the sandfly density were calculated at different months and in different breeding habitats. Results A total of 406 light traps were set at sandfly surveillance sites in Henan Province from May to September, 2023, and a total of 3 137 female sandlies were captured, with an average density of 7.73 sandlies/(light·night). A total of 1 494 Phlebotomus chinensis sandflies were captured, including 1 222 female sandflies, with an average density of 3.01 sandflies/(light·night), and the highest density of P. chinensis was found in Gongyi City [17.00 sandflies/(light·night)]. A total of 5 544 sandflies were captured using the human capture method, including 230 P. chinensis, and the density of P. chinensis appeared a unimodal distribution, with a peak in early July [5.81 sandflies/(light·night)]. Among different breeding habitats, the highest P. chinensis density was detected in pigpens [4.50 sandflies/(light·night)]. Conclusions P. chinensis was predominantly distributed in hilly areas of northern and central-western Henan Province in 2023, and the sandfly density appeared a unimodal distribution. Intensified monitoring of visceral leishmaniasis vectors is recommended.

Objective To characterize the species of common sandflies in Henan Province using DNA barcoding with cytochrome c oxidase subunit I (COI) gene as the molecular marker, and to analyze the genetic polymorphisms of sandflies, so as to provide insights into visceral leishmaniasis prevention and control in Henan Province. Methods Sandfly specimens were sampled from 13 sandflies surveillance sites from 2021 to 2023 in Anyang City, Zhengzhou, Luoyang and Xuchang cities (Zhengzhou-Luoyang-Xuchang areas) where visceral leishmaniasis cases were reported and in Jiaozuo and Xinxiang cities (Jiaozuo-Xinxiang areas) without visceral leishmaniasis cases reported. Genomic DNA was extracted from a single sandfly, and COI gene was amplified. The amplification product was subjected to bidirectional sequencing. Following sequence assembly, the species of sandflies was characterized through sequence alignment using the BLAST tool. The intra-specific and inter-specific genetic distances of sandflies were estimated among different areas using the software Mega 11, and phylogenetic trees were created. The polymorphisms of nucleotide sequences in the sandflies COI gene were estimated using the software DnaSP. The fixation index (F_ST) of different geographical isolates of sandflies was calculated using the Arlequin software, and the gene flow value (Nm) was used to measure the gene flow in the sandflies populations. In addition, the population genetic structure of different geographical populations of Phlebotomus chinensis was analyzed using the STRUCTURE software. Results A total of 978 sandflies were collected from 13 sandflies surveillance sites in Zhengzhou-Luoyang-Xuchang areas, Jiaozuo-Xinxiang areas and Anyang City of Henan Province from 2021 to 2023, and 475 sandflies were randomly sampled for subsequent detections. A total of 304 Ph. chinensis, 162 Se. squamirostris and 9 Se. bailyi were identified based on molecular biological detection of the COI gene, and Se. bailyi was reported for the first time in Henan Province. The intraspecific genetic distances of sandflies were 0.000 to 0.040, and the inter-specific genetic distances ranged from 0.133 to 0.161. Phylogenetic analysis revealed that each of the three sandfly species was clustered into a clade. The genetic polymorphisms of Ph. chinensis populations varied among different areas, with the highest haplotype diversity (0.966 ± 0.007) and the greatest nucleotide diversity (0.011) in Zhengzhou-Luoyang-Xuchang areas, and the lowest haplotype diversity (0.720 ± 0.091) and nucleotide diversity (0.004) in Anyang City. The dominant haplotype of Ph. chinensis populations was Pch_Hap_2 in Anyang City and Jiaozuo-Xinxiang areas, with moderate genetic differentiation (0.05 < F_ST < 0.15) and frequent gene exchange (Nm value > 1) between Ph. chinensis populations sampled from Anyang City, and Jiaozuo-Xinxiang areas. Population genetic structure analysis showed that the dominant component of Ph. chinensis populations was K5 in Anyang City and Jiaozuo-Xinxiang areas. No obvious dominant haplotype was observed in Ph. chinensis populations sampled from Zhengzhou-Luoyang-Xuchang areas, which had very high genetic differentiation (F_ST > 0.25) and little gene exchange (Nm value < 1) with Ph. chinensis populations from Anyang City, and Jiaozuo-Xinxiang areas, with K3 as the dominant component. In addition, there was no significant difference in the genetic polymorphism level among Se. squamirostris populations from the three areas. Conclusions There are Ph. chinensis, Se. squamirostris and Se. bailyi in Henan Province, and S. bailyi is recorded for the first time in Henan Province by molecular biological assays. There are different levels of genetic differentiation and gene exchange among P. chinensis populations in different areas of Henan Province.