Objective To explore the expression of serum miR-410-3p in patients with rheumatoid arthritis(RA)and its relationship with knee soft tissue lesions.Methods A total of 89 RA patients admitted to our hospital were selected and divided into the active group(42 cases)and the remission group(47 cases)according to disease activity score in 28 joints(DAS28).In addition,52 healthy volunteers underwent physical examination during the same period in our hospital were selected as the healthy group.The expression level of serum miR-410-3p was detected by RT-PCR,the lesions of knee soft tissue was examined by ultrasound,and the relationship between the expression of serum miR-410-3p and knee soft tissue lesions was analyzed by Pearson.Results The expression levels of serum miR-410-3p of patients in the active group and the remission group were lower than that in the healthy group(P<0.05),and the expression level of serum miR-410-3p of patients in the active group was lower than that in the remission group(P<0.05).The cartilage thicknesses of medial and lateral ankle of patients in the active group and the remission group were smaller than those in the healthy group(P<0.05),and the above indexes in the active group were smaller than those in the remission group(P<0.05).The depths of suprapatellar bursa fluid and synovial thicknesses of patients in the active group and the remission group were greater than those in the healthy group(P<0.05),and the depth of suprapatellar bursa fluid and synovial thickness of patients in the active group were greater than those in the remission group(P<0.05).The level of serum miR-410-3p in RA patients was positively correlated with the depth of suprapatellar bursa fluid and synovial thickness(P<0.05),and negatively correlated with the cartilage thicknesses of medial and lateral ankle(P<0.05).Conclusion Serum miR-410-3p expression level in RA patients is decreased,which was closely related to knee soft tissue lesions,detecting the changes of serum miR-410-3p level may provide a reference for the evaluation of knee soft tissue lesions.

Objective To explore the selection rules of acupuncture and moxibustion for treating ovarian dysfunction-related diseases by applying data mining technology.Methods Computer searches were conducted to find clinical research literature on acupuncture and moxibustion for ovarian reserve dysfunction-related diseases(including diminished ovarian reserve,premature ovarian insufficiency,premature ovarian failure)in major databases,such as China National Knowledge Infrustructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and China Science and Technology Journal Database(VIP),Excel 2021 was used to establish a prescription database of acupoints selection,and SPSS Modeler 18.0 and SPSS Stastics 26.0 software were used to analyse the frequency,meridian tropism,site,special acupoints,analysis of association rule,and cluster analysis of acupoints to study the rules of acupuncture and moxibustion for treating ovarian reserve dysfunction-related diseases.Results A total of 215 articles were screened to meet the requirements,in which,96 acupoints were used,with a total frequency of 2 110 times.The high-frequency used acupoints were Guanyuan(RN4),Sanyinjiao(SP6),and Shenshu(BL23),etc,.The commonly used meridians were the conception vessel(CV)and bladder meridian of foot-taiyang,and the acupoints were mostly located in the abdomen and lower limbs,with the majority being the five-shu point and the yuan front-mu points.The core acupoints and four effective clusters were analysed.Conclusion The acupoint selection of acupuncture and moxibustion for ovarian reserve dysfunction-related diseases focuses on tonifying qi and blood,cultivating the vital essence and tonifying the kidneys.Most of the meridians related to reproduction were selected in this method,which aiming at regulating menstruation and tonifying blood,and pre-cultivating its loss.This research focuses on the matching of neighboring point and distant point selection,and pays attention to the use of specific acupoints,and treates multiple organs simultaneously.

This study investigated the prevalence of Borrelia burgdorferi,Anaplasma phagocy tophilum,Rickettsia typhi,Orientia tsutsugamushi,Leptospira interrogans,Francisella tularensis,and Babesia spp.in small mammals in the Qinghai plateau region,to provide a scientific basis for the prevention and control of local zoonotic diseases.Small mammals were cap-tured with snap traps at six sampling sites in the Qinghai plateau region.Liver,spleen,and kidney tissues were collected for detection of six bacterial pathogens with real-time PCR.Conventional PCR(cPCR)was used for Babesia detection,and the positive PCR products were sequenced and analyzed.The differences in pathogen detection rates among species and habitats were analyzed with x2 test or Fisher's exact test.In to-tal,235 small mammals from 15 species were captured.B.burgdorferi,L.interrogans,and Babesia were detected in 11 spe-cies of small mammals,whereas A.phagocytophilum,R.typhi,O.tsutsugamushi,and F.tularensis were not detected.B.burgdorferi was detected in 41 small mammals from nine species(Cricetulus longicaudatus,Apodemus peninsulae,Ochotona curzoniae,Mus m usc ulus,Meriones meridians,Microtus arvalis,Cricetidae,Ochotona cansus,and Allactaga sibirica),with an infection rate of 17.45％(41/235).L.interrogans was detected in eight small mammals from four species(C.longicaudatus,M.musculus,M.arvalis,and Microtus oeconomus),with an infection rate of 3.40％(8/235).Babesia was detected in only one Mustela altaica,with an infection rate of 0.85％(1/235).Statistically significant differences were ob-served in the detection rates of pathogens among small mammal species(x2=200.54,P＜0.05).Among habitats,the detection rate of B.burgdorferi was highest in the forest(Fisher's exact test,P＜0.05).B.burgdorferi and L.interrogans co-infection was observed in three M.arvalis and two C.longicaudatus.In addition,one Babesia sequence was obtained,which clustered with Babesia vulpes in the phylogenetic tree.B.burgdorferi,L.interrogans,and Babesia were the main pathogens prevalent in small mammals in the Qinghai plateau region and have potential to cause human diseases.Local authori-ties should strengthen the surveillance of corresponding zoonotic diseases,and formulate corresponding prevention and control measures.

Objective:To investigate the efficacy and safety of ixazomib combined with thalidomide and dexamethasone in the treatment of multiple myeloma(MM).Methods:The clinical data of 60 MM patients admitted to our center from January 2019 to June 2022 were analyzed retrospectively,including 43 newly diagnosed patients and 17 patients with recurrence and progression.All patients were treated with ixazomib combined with thalidomide and dexamethasone,and completed 2 to 7 treatment cycles.Results:The overall response rate(ORR)of all patients was 98.3％.Among them,53 patients completed 4 treatment cycles,and the ORR was 86.8％.Seventeen patients completed the whole treatment cycle,with curative effect reaching 88.2％achieving very good partial response and above,and 52.9％achieving complete response and above.Albumin and β2-microglobulin of all patients had been improved rapidly after treatment.The deadline was August 31,2022.The median follow-up time was 14(3-24)months,and overall survival(OS)rate was 86.67％.The OS rate of patients with recurrence and progression was significantly lower than that of newly diagnosed patients(P＜0.05).The most common adverse reaction of hematology was lymphopenia(53.3％),followed by anemia(33.3％).The most common non-hematological adverse reaction was fatigue(68.33％),followed by peripheral neuropathy(31.67％).Conclusion:Ixazomib combined with thalidomide and dexamethasone is effective in the treatment of MM,with good short-term efficacy,survival and safety.However,its long-term efficacy needs further observation.

It has been well documented that exercise can improve bone metabolism, promote bone growth and development, and alleviate bone loss. MicroRNAs (miRNAs) are widely involved in the proliferation and differentiation of bone marrow mesenchymal stem cells, osteoblasts, osteoclasts and other bone tissue cells, and regulation of balance between bone formation and bone resorption by targeting osteogenic factors or bone resorption factors. Thus miRNAs play an important role in the regulation of bone metabolism. Recently, regulation of miRNAs are shown to be one of the ways by which exercise or mechanical stress promotes the positive balance of bone metabolism. Exercise induces changes of miRNAs expression in bone tissue and regulates the expression of related osteogenic factors or bone resorption factors, to further strengthen the osteogenic effect of exercise. This review summarizes relevant studies on the mechanism whereby exercise regulates bone metabolism via miRNAs, providing a theoretical basis for osteoporosis prevention and treatment with exercise.
Humans ; MicroRNAs/metabolism* ; Osteogenesis/genetics* ; Cell Differentiation ; Osteoblasts ; Bone Resorption/metabolism*

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota.However,the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations.A well-controlled envi-ronment is thus necessary to reduce undesirable confounding effects,and recapitulate age-dependent changes in the gut microbiota of healthy primates.Herein we performed 16S rRNA gene sequenc-ing,characterized the age-associated gut microbial profiles from infant to elderly crab-eating maca-ques reared in captivity,and systemically revealed the lifelong dynamic changes of the primate gut microbiota.While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium,the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants,underlining their potential role in host development.Importantly,topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity,and its tremendous decline with age could probably be linked to healthy aging.Moreover,we identified key driver microbes responsible for such age-dependent network changes,which were further linked to altered metabolic functions of lipids,carbohydrates,and amino acids,as well as phenotypes in the microbial community.The current study thus demon-strates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota,and provides new insights into their roles in the development and healthy aging of their hosts.

ObjectiveTo identify the protective effect and possible mechanism of Gandou Fumu decoction （GDFMD） on liver fibrosis in mice with Wilson's disease. MethodA total of 50 homozygous TX^J mice were randomly divided into five groups， with 10 mice in each group. Ten wild-type mice were selected as a normal group. The GDFMD high， medium， and low-dose groups were given 13.92， 6.96， 3.48 g·kg^-1 of GDFMD， respectively. The penicillamine group were given 0.1 g·kg^-1 of penicillamine. The model group and the normal group were given the same volume of 0.9% sodium chloride solution once a day for 4 consecutive weeks. The enzyme-linked immunosorbent assay （ELISA） method was performed to detect serum superoxide dismutase （SOD） activity and malondialdehyde （MDA） content. Corresponding kits were used to detect the mitochondrial adenine triphosphate （ATP） content and Na⁺-K⁺-ATPase activity in liver tissues. Hematoxylin-eosin （HE） and Masson staining were used to observe the pathological morphology of liver tissue， and transmission electron microscope was used to observe ultrastructural changes of liver tissues in mice. Western blot was used to detect the c-Jun N-terminal kinase， the phosphorylated protein， and the expressions of Caspase-3， B cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax） in c-Jun N-terminal kinase （JNK） signaling pathway. ResultCompared with the normal group， MDA content increased and SOD activity decreased in the model group （P<0.05）. Compared with the model group， SOD activities in the GDFMD high-， medium-， and low-dose groups and the penicillamine group significantly increased （P<0.01）， and MDA content significantly decreased （P<0.05， P<0.01）. Compared with the normal group， ATP content and Na⁺-K⁺-ATPase activity significantly decrease in the model group （P<0.05）. Compared with the model group， ATP content and Na⁺-K⁺-ATPase activity in the GDFMD medium and high-dose groups and the penicillamine group significantly increased （P<0.05， P<0.01）. The results of the pathological morphology of liver tissue showed that a large number of liver cells degeneration and necrosis， inflammatory cell infiltration， unclear liver lobule structure， and collagen fiber deposition were observed in the model group. Transmission electron microscopy showed that the number of mitochondria in liver tissues significantly reduced， the mitochondria were locally damaged， and the cristae of mitochondria were broken even disappear in the model group. The pathological morphology of liver tissue and mitochondrial structure recovered to varying degrees after medicinal intervention. The results of Western blot suggested that， compared with the normal group， the expression levels of phosphorylation-JNK （p-JNK）， p-JNK/JNK， Caspase-3， and Bax in the liver tissues were up-regulated， while the expression of Bcl-2 was down-regulated in the model group （P<0.05）. The expression levels of p-JNK， p-JNK/JNK， Caspase-3 and Bax were down-regulated and the expression of Bcl-2 was up-regulated in the GDFMD high and medium-dose groups and the penicillamine group （P<0.01）. ConclusionGDFMD can alleviate oxidative stress damage and recover mitochondrial function of TX^J mice with liver fibrosis. The mechanism of GDFMD may be related to regulating the JNK signaling pathway and downstream factors and inhibiting cell apoptosis.

Hepatolenticular degeneration（HLD），also known as Wilson disease （WD）， is a genetic disorder characterized by copper metabolism disorder caused by ATP7B gene mutation. Specifically， due to the ceruloplasmin synthesis disorder induced by gene mutation，copper cannot be excreted through bile，which results in pathological deposition of copper in various organs and damage to organs such as the brain and the liver. The incidence of WD in Chinese is significantly higher than that in the world. Copper chelating agents， such as D-penicillamine and dimercaptosuccinic acid， are used as the main therapeutic agents in western medicine. However， many clinical adverse events limit the application of these drugs. Traditional Chinese medicine （TCM） has its characteristics in the treatment of WD. As confirmed by long-term research on TCM clinical diagnosis and treatment，MD has become TCM dominant disease. In spite of many views about the etiology and pathogenesis of WD，a consensus has not been reached so far. Based on the theory of latent pathogen in TCM and the pathological mechanism of excessive deposition of copper ions in the body，this study proposed that latent toxin is the key etiology of WD，and further elaborated that the latent toxin of WD was inherited from parents and occurred in children and adolescents，which was hidden in the liver and the kidney and damaged the brain. The latent toxin， Yang in nature and dispersing in property， is prone to transform into dampness-heat to block Qi movement and produce phlegm leading to stasis. Furthermore， this study determined latent toxin blocking collaterals as the basic pathogenesis of WD and revealed the complex clinical manifestations of latent toxin blocking collaterals such as liver collaterals，brain collaterals，kidney collaterals，spleen collaterals，stomach collaterals，lung collaterals，heart collaterals， and uterus collaterals. Treatment should follow the basic therapeutic principles of resolving pathogens，removing toxins， and dredging collaterals. This study is expected to provide a theoretical basis for syndrome differentiation and treatment of WD in TCM.

Objective To investigate the role of phosphoglycerate kinase 1 (PGK1) in tumorigenesis and its potential post-translational modification sites were investigated by bioinformatics method and molecular biology experimental techniques, in order to provide evidence for PGK1 as a hepatocellular carcinoma ( HCC) diagnostic biomarker and therapeutic target. Methods From pan-cancer's point of view, 10 967 samples were obtained from the cancer genome database TCGAs, and the expression of PGK1 in different tumors was explored by using cBioPortal and UALCAN analysis tools; Focusing on HCC, the expression differences of PGK1 in hepatocellular carcinoma tumor tissues and normal tissues were further analyzed by using GEO database analysis, Real-time PCR, Western blotting and cell invasion assay;The String database was used to analyze the protein-protein interaction network and gene set enrichment analysis; The CSS-Palm database and bioinformatics method were used to predict protein post-translational modification sites on PGK1. Results The PGK1 gene was abnormally amplified and overexpressed in various solid tumors, including hepatocellular carcinoma, and overexpression of PGK1 was correlated with a poor prognosis in hepatocellular carcinoma. Multiple novel posttranslational modifications were existed on PGK1. Conclusion PGK1 is closely related to the occurrence and development of various cancers including HCC and glycolytic metabolism abnormalities. Epigenetic modifications can regulate PGK1 and affect its cellular function in HCC.