ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

Objective:To analyze the prevalence of the Dabie bandavirus among rats in Taipusi Banner, Xilingol League, Inner Mongolia Autonomous Region.Methods:The cytochrome b gene for the identification of rat species was amplified. Real-Time RT-PCR and RT-PCR were used to amplify and sequence DBV positive rat tissues and detected by XilinGol League Center for Disease Control and Prevention, and the gene evolution was analyzed.Results:The rat was identified as Spermophilus dauricus. Through molecular detection on 20 samples, 15 samples showed positive result in Real Time RT-PCR nucleic acid test, and 7 samples showed positive result in RT-PCR nucleic acid test. Seven base sequences were obtained through sequencing, and they were compared with those in the National Center for Biotechnology Information (NCBI) of the United States by BLAST. It was determined that they were the S gene sequences of DBV. It has been uploaded to GenBank with serial numbers PV231886, PV231887 and PV231888.Conclusions:DBV was detected for the first time in the mice of Inner Mongolia Autonomous Region. In future work, monitoring of DBV carried by rodents and ectoparasites such as ticks and fleas in this area should be strengthened. Publicity and education on severe fever with thrombocytopenia syndrome should be carried out in this area to improve the local medical system′s ability to identify such cases, ensuring early detection, early diagnosis, and early treatment, and reducing the occurrence of human cases and clustered outbreaks.

Aim To investigate the mechanism of Guanxinning injection regulating cardiac immune mi-croenvironment to improve myocardial infarction in mice.Methods In this study,MI model was estab-lished by permanent ligation of left anterior descending coronary artery in mice.The mice were divided into five groups:sham operation group,model group,Guanxinning injection low dose group,Guanxinning in-jection high dose group and positive drug captopril group.Hearts were weighed,heart tissues were collect-ed,and Masson staining was used for pathological anal-ysis of heart tissues;immunofluorescence staining was used to detect apoptosis and CCL21 expression in the infarct border zone;flow cytometry was used to detect the proportion of immune cells in myocardial ischemia tissues and lymph nodes;PCR was used to detect CCL21 expression in heart and in vitro human lymphat-ic endothelial cells(HLEC).Results Compared with the model group,the low and high dose groups of Guanxinning injection significantly improved cardiac hypertrophy.Apoptosis in the border zone of myocardi-al infarction was reduced in the low and high dose groups of Guanxinning injection and captopril group.Compared with the model group,the proportion of leu-kocytes in the infarct border zone was dreduced and the proportion of CD4+T cells,Treg cells,and CD8+T cells in the mediastinal lymph nodes and infarct border zone of the heart was regulated in the low and high dose groups of Guanxinning injection;CCL21 secretion by the heart and lymphatic vessels increased.Conclu-sions Guanxinning injection can significantly improve cardiac hypertrophy and fibrosis in MI mice,reduce ap-optosis in the infarct border zone,and play a role in an-ti-myocardial ischemia injury by promoting CCL21 ex-pression in lymphatic vessels to regulate the proportion of mediastinal lymph nodes and cardiac T cells after myocardial infarction.

This study was aimed at analyzing the biotypes and genetic diversity characteristics of five non-major Brucella species,to provide a scientific basis for understanding the species diversity of Brucella and strengthening pathogen monitoring and control.According to the biotypes(species,hosts,isolation locations,and time)and MLVA-16 genotypes(MLVA-16 lo-cus data,MLVA-11 genotypes)of five non-major pathogenic Brucella in the international MLVA database,we used Bionu-merics 8.0 software and PHYLOVIZ2.0 online software to analyze the geographical origin and genetic diversity characteristics of strains.A total of 227 strains were studied,including 121 Brucella ceti,47 B.pinnipedialis,37 Brucella ovis,11 B.mi-croti,and Brucella neotomae.The greatest host diversity was observed for B.ceti,followed by B.pinnipedialis and B.mi-croti.B.ceti was distributed in European and South American countries;B.pinnipedialiswas distributed in Europe;and B.microti.was distributed in the Czech Republic,Austria,and Hungary in Central Europe.B.ovis was widely distributed in Af-rica,Argentina,Australia,Brazil,Greece,the United States,Spain,and France.The MLVA-11 genotypes of different types of Brucella showed high polymorphism and large differences,thus suggesting that the strains have different geographical ori-gins.MST analysis indicated that the studied strains were divided into four branches(BCⅠ-Ⅳ),among which B.ceti was di-vided into two different branches(BC-Ⅰ and BC-Ⅱ),the strains of other types formed different branches(or sub-branches),and the strains of different types showed clear regional and dominant host characteristics.Genetic correlation analysis of strains of the Brucella genus revealed that non-major pathogenic Brucella had clear genetic,distribution,and host spectrum differ-ences with respect to four classical pathogenic Brucella species.Five non-major pathogenic Brucella strains presented unique genetic evolutionary patterns,geographical distributions,and host tropism characteristics,thereby providing new insight for understanding the biological and genetic diversity of those Brucella strains.

Aim To investigate the mechanism of Guanxinning injection regulating cardiac immune mi-croenvironment to improve myocardial infarction in mice.Methods In this study,MI model was estab-lished by permanent ligation of left anterior descending coronary artery in mice.The mice were divided into five groups:sham operation group,model group,Guanxinning injection low dose group,Guanxinning in-jection high dose group and positive drug captopril group.Hearts were weighed,heart tissues were collect-ed,and Masson staining was used for pathological anal-ysis of heart tissues;immunofluorescence staining was used to detect apoptosis and CCL21 expression in the infarct border zone;flow cytometry was used to detect the proportion of immune cells in myocardial ischemia tissues and lymph nodes;PCR was used to detect CCL21 expression in heart and in vitro human lymphat-ic endothelial cells(HLEC).Results Compared with the model group,the low and high dose groups of Guanxinning injection significantly improved cardiac hypertrophy.Apoptosis in the border zone of myocardi-al infarction was reduced in the low and high dose groups of Guanxinning injection and captopril group.Compared with the model group,the proportion of leu-kocytes in the infarct border zone was dreduced and the proportion of CD4+T cells,Treg cells,and CD8+T cells in the mediastinal lymph nodes and infarct border zone of the heart was regulated in the low and high dose groups of Guanxinning injection;CCL21 secretion by the heart and lymphatic vessels increased.Conclu-sions Guanxinning injection can significantly improve cardiac hypertrophy and fibrosis in MI mice,reduce ap-optosis in the infarct border zone,and play a role in an-ti-myocardial ischemia injury by promoting CCL21 ex-pression in lymphatic vessels to regulate the proportion of mediastinal lymph nodes and cardiac T cells after myocardial infarction.

Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

This study investigated the prevalence of hepatitis E virus(HEV)in rodents within the Inner Mongolia Autonomous Region.In 2024,liver,spleen,kidney,and lung tissue samples were collected from rodents in 11 leagues and cities across the Inner Mongolia Autonomous Region,including Hohhot,Baotou,Hulunbuir,Xing'an League,Tongliao,Chifeng,Xilin Gol League,Ulan-qab,Ordos,Bayannur,and Wuhai.Nested PCR(RT-PCR)was used to detect the conserved regions of the HEV open reading frame 1(ORF1)gene.The RT-PCR-positive products were sequenced,and phylogenetic and homology analysis of the obtained sequences was performed.A total of 816 rodents were captured in this investigation,including 319 Rattus norvegicus(39.09%,319/816),206 Musmusculus(25.25%,206/816),and 140 Mongolian gerbils(17.16%,140/816).The HEV infection rate among rodents in the In-ner Mongolia region was 3.68%(30/816).Sequencing of the RT-PCR-positive results and analysis of the nucleotide sequences yielded 30 HEV-positive rodent samples.Phylogenetic analysis identified these sequences as belonging to the HEV-C1 genotype.The prevalence of HEV was observed in brown rats(Rattus norvegicus)in five leagues and cities within the Inner Mongolia region,includ-ing Xing'an League,Chifeng City,Hulunbuir City,Xilin Gol League,and Tongliao City,with infection rates of 16.67%,10.00%,5.98%,3.30%,and 2.50%,respectively.Brown rats,a species of house rats,frequently inhabit areas near human residences and have close interactions with humans and livestock.Studies have shown that multiple subtypes of HEV can cause zoonotic infections.Therefore,strengthening the monitoring of pathogens carried by rodents in residential environments and optimizing the prevention and control of rodent-borne diseases will be essential.Timely dissemination of relevant infectious disease knowledge to local communities will also be crucial,to decrease the risk of human infection.

Oncolytic viruses can selectively infect and kill tumor cells.Since China's first oncolytic virus product re-combinant human 5 adenovirus H101 was approved for market in 2005,four oncolytic virus products have entered the market globally.More than 200 clinical trials of oncolytic virus therapies have been conducted worldwide.However,the number of globally approved indications for oncolytic virus products remains limited,and the potential patient populations and therapeutic mechanisms require further clinical investigation.To further optimize the clinical trial design of oncolytic virus products in China,this consensus was developed based on the"Guiding principles for clinical trial design of oncolytic virus drugs(trial version)"issued by the National Medical Products Administration(NMPA).Based on the medicine method,from the perspective of the mechanism of action of oncolytic virus,development indication,clinical application mode,clinical trial biology and pharmacodynamic detection,etc.,multidisciplinary expert meeting discussion and ques-tionnaire survey were carried out based on the considerations and related contents of the current clinical trial design of oncolytic virus.After three rounds of opinion collection,combing and summarizing,the"Chinese expert consensus on the key points of oncolytic virus clinical trial design(2024 edition)"was formed,aiming to provide references for sponsors and re-searchers of clinical trials of oncolytic virus products in China,help related products quickly go to market,and achieve new breakthroughs in tumor treatment.

Objective:To analyze the prevalence of the Dabie bandavirus among rats in Taipusi Banner, Xilingol League, Inner Mongolia Autonomous Region.Methods:The cytochrome b gene for the identification of rat species was amplified. Real-Time RT-PCR and RT-PCR were used to amplify and sequence DBV positive rat tissues and detected by XilinGol League Center for Disease Control and Prevention, and the gene evolution was analyzed.Results:The rat was identified as Spermophilus dauricus. Through molecular detection on 20 samples, 15 samples showed positive result in Real Time RT-PCR nucleic acid test, and 7 samples showed positive result in RT-PCR nucleic acid test. Seven base sequences were obtained through sequencing, and they were compared with those in the National Center for Biotechnology Information (NCBI) of the United States by BLAST. It was determined that they were the S gene sequences of DBV. It has been uploaded to GenBank with serial numbers PV231886, PV231887 and PV231888.Conclusions:DBV was detected for the first time in the mice of Inner Mongolia Autonomous Region. In future work, monitoring of DBV carried by rodents and ectoparasites such as ticks and fleas in this area should be strengthened. Publicity and education on severe fever with thrombocytopenia syndrome should be carried out in this area to improve the local medical system′s ability to identify such cases, ensuring early detection, early diagnosis, and early treatment, and reducing the occurrence of human cases and clustered outbreaks.

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL