ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

Objective: To explore the prevalence of bone defect and alveolar bone thickness changes in the mandibular incisors of untreated adults and post-orthodontic treatment adults, with the aim of providing strategies for preventing and managing alveolar bone defects during orthodontic treatment. Methods: This study was reviewed and approved by the Medical Ethics Committee. Clinical records, panoramic radiographs, cephalometric radiographs, and cone beam computed tomography (CBCT) images and informed consent were obtained for 150 untreated adults and 150 post-orthodontic adults. The untreated adults and post-orthodontic adults were respectively divided into three subgroups: skeletal ClassⅠ, Class Ⅱ and Class Ⅲ, with 50 cases per subgroup. Meanwhile, 60 cases with completeness of pre- and post-orthodontic data were enrolled from 150 post-orthodontic adults, including 20 cases each of skeletal ClassⅠ, Class Ⅱ, and Class Ⅲ. Cephalometric radiographs were imported into Dolphin software to measure skeletal parameters. CBCT images were imported into Mimics software to assess alveolar bone defects and to measure alveolar bone thickness of mandibular incisors among three groups: 150 untreated adult groups, 150 post-orthodontic groups and the pre- and post-treatment status of 60 patients selected from the latter group. Results: Untreated adult patients: the prevalence of labial dehiscence and fenestration in the mandibular incisors was higher than that on the lingual side among skeletal ClassⅠ, Ⅱ, and Ⅲ malocclusion patients, and there was a statistically significant difference in the alveolar bone thickness of the mandibular incisors among the three classes. Post-orthodontic treatment adults: for skeletal ClassⅠ and Ⅱ patients, the prevalence of lingual bone dehiscence in the mandibular incisors was significantly higher in the extraction groups than in the non-extraction groups; correspondingly, the lingual alveolar bone was also thinner in the extraction groups; Class Ⅱ non-extraction patients showed a higher prevalence of labial bone fenestration but a lower prevalence of lingual bone fenestration in mandibular incisors compared to Class Ⅱ extraction patients; the orthodontic-orthognathic combined treatment group showed significantly higher prevalence of labial/lingual bone dehiscence and thinner alveolar bone at multiple sites in the mandibular incisors compared to the camouflage group in skeletal Class Ⅲ patients. Comparison of mandibular incisor bone defects and thickness before and after orthodontic treatment in adult patients: in skeletal ClassⅠ and Ⅱ patients treated with premolar extraction and Class Ⅲ patients treated with orthodontic-orthognathic combined treatment, the lingual alveolar bone of mandibular incisors exhibited significant resorption and thinned after treatment, and this was accompanied by an increased prevalence of dehiscence; in non-extraction patients, ClassⅠ non-extraction patients showed thinning of the crestal-labial bone and apical-lingual bone, Class Ⅱ patients showed thinning of the crestal-labial bone and middle-labial bone of the mandibular incisors, along with an increased prevalence of dehiscence Conclusion In malocclusion adults, alveolar bone defects were already present in the mandibular incisors before orthodontic treatment. The alveolar bone defects and thickness in mandibular incisors among post-orthodontic adults were influenced by the treatment plan and Class of skeletal malocclusion.

Bruton's tyrosine kinase inhibitors (BTKi) are a class of novel small-molecule targeted antitumor drugs used to treat B-cell malignancies. However, safety issues associated with BTKi may lead to treatment interruption, compromising their efficacy. To promote the standardized management of safety in BTKi treatment, Evidence-Based Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, Expert Committee on Lymphoma of Chinese Society of Clinical Oncology, Expert Committee on Leukemia of Chinese Society of Clinical Oncology, Integrated Cancer Cardiology Branch of China Anti-Cancer Association, Hematology Branch of the Chinese Medical Association, and Hospital Pharmacy Professional Committee of the Cross-Straits Medicine Exchange Association formulated the Evidence-based Expert Consensus on the Clinical Management of Safety of Bruton′s Tyrosine Kinase Inhibitors (2024), which was published in the Chinese Journal of Cancer Research in June 2024. It covered 9 clinical issues in the following 3 domains: (1) the management of common adverse reactions of BTKi such as bleeding, cardiovascular events, hematological toxicity, infections, rashes, diarrhea, and arthralgia; (2) the management of drug-drug interactions; (3) management guidance for special populations. This consensus provides evidence-based recommendations for the safety management of BTKi medication in clinical practice. This article provides an interpretation and evidence summary of the consensus in Chinese, aiming to facilitate its implementation in China, enhance the safety management of BTKi treatment, and improve patient outcomes.

Objective:To investigate molecular mechanism of Helicobacter pylori(H.pylori)-mediated neutrophil apoptosis disorder.Methods:Neutrophils extracted from peripheral blood of healthy adults were used as research subjects,and H.pylori stan-dard strain NCTC11637 was added to culture system to construct a model of in vitro infection,which was divided into control group(with PBS or medium treatment),H.pylori group(H.pylori co-cultivated with neutrophils at ratio of 10∶1).After a certain time of in-fection,apoptosis-related molecules of neutrophils were detected by flow cytometry,ELISA and Western blot,respectively.Results:Cytokines IL-1β,IL-6 and TNF-α were secreted significantly higher in H.pylori group than control group,apoptosis rate was signifi-cantly lower than control group,apoptosis-related proteins Caspase-3 and Caspase-8 were higher than control group,but their activa-tion level were lower than control group.Conclusion:H.pylori infection may prolong neutrophil survival by inhibiting apoptotic pro-cess of neutrophils through inhibiting activation of Caspase-3/8.

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

Objective:To compare the changes in spherical equivalent (SE) and axial length (AL) between children with axial myopia and refractive myopia.Methods:A prospective cohort study was conducted.A total of 1 738 students from grades 1 to 6 were recruited from two consistent 9-year schools in the Binhai New Area of Tianjin using cluster random sampling.Visual acuity, refractive status, and ocular biological parameters were measured from February to May in 2018 and 2021.Participants were categorized into subgroups as follows: low, moderate, and high myopia based on SE; longer AL group and shorter AL groups based on AL; and steeper cornea and flatter cornea groups based on corneal curvature radius (CCR). Myopic children were further classified into the following groups: axial myopia (longer AL and flatter cornea), refractive myopia (shorter AL and steeper cornea), mixed myopia (longer AL and steeper cornea), and non-axial non-refractive myopia (shorter AL and flatter cornea). Changes in SE (ΔSE) and AL (ΔAL) at the end of the follow-up period were compared among the different classification groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY-39). Written informed consent was obtained from the guardians of all participants.Results:The ΔSE in the longer AL group was (-1.57±1.52)D, which was significantly greater than (-1.17±1.47)D in the shorter AL group ( t=3.99, P<0.01). The ΔAL in the steeper cornea group was (0.92±0.50)mm, which was significantly greater than (0.86±0.54)mm in the flatter cornea group ( t=-2.12, P=0.04). Among children aged 10-12 years, males, and the low myopia, SE progression was faster in those with longer AL compared to shorter AL, with statistically significant differences ( t=2.66, 3.31, 3.90; all P<0.05). In children aged 10-12 years, AL growth was faster in the longer AL group than in the shorter AL group, with a statistically significant difference ( t=-1.29, P=0.04). Among females and the low myopia, AL growth was faster in those with steeper corneas than in those with flatter corneas, with statistically significant differences ( t=-3.22, -2.43; both P<0.05). Refractive myopia had a smaller ΔSE than axial myopia and the difference was statistically significant ( P<0.05). Within the low myopia, SE progression was greater in axial myopia than in refractive myopia, with a statistically significant difference ( P<0.05). Conclusions:Among myopic children, those with longer axial lengths exhibit faster SE progression, while those with steeper corneas show faster axial elongation.Among children with low myopia, axial myopia is associated with a greater risk of SE progression than refractive myopia.

Objective:To study the role of cadherin 1 (CDH1) gene DNA methylation in autoimmune thyroiditis (AIT) in population from different water-iodine regions.Methods:From May to June 2019, the information of AIT cases and healthy individuals in Shandong Province were collected in three types of water-iodine regions: iodine-fortification (IF) region, iodine-adequate (IA) region and iodine-excess (IE) region. A case-control study design was applied to match 176 AIT cases (case group) with age, gender, body mass index, and place of residence in a 1 ∶ 1 ratio to 176 healthy individuals (control group). Fasting urine and whole blood samples were collected to test the contents of urinary iodine, thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH)], and serum iodine. The DNA methylation levels of the target region of the CDH1 gene and its four CpG sites in whole blood were determined using methylation sequencing technology for target regions (MethylTarget TM). Results:The DNA methylation level of the target region of CDH1 gene in the case group was 0.832 ± 0.044, and that in the control group was 0.828 ± 0.049, there was no statistically significant difference between the two groups ( t = 0.76, P = 0.448). There was no statistically significant difference in DNA methylation levels of the four CpG sites in the target region of CDH1 gene between the case group and the control group ( P > 0.05). There was no statistically significant difference in the DNA methylation level of the CDH1 gene target region between the case group and the control group in IF, IA and IE regions ( P > 0.05). The detection results of DNA methylation levels at CpG sites in the target region of CDH1 gene in different water iodine regions showed that the DNA methylation level at site 83 in case group in IF region was higher than that in the control group ( t = 2.30, P = 0.023). However, there was no statistically significant difference in the DNA methylation levels of the four CpG sites between the case group and the control group in IA and IE regions ( P > 0.05). The DNA methylation level of CDH1 gene target region in AIT patients was not significantly correlated with urinary iodine, serum iodine, and serum FT 3, FT 4, and TSH contents ( P > 0.05), but was significantly negatively correlated with age ( r =-0.19, P = 0.014). Conclusions:The DNA methylation level at CpG site 83 of CDH1 gene in AIT patients in IF region is significantly higher than that in control population, indicating that DNA methylation at this locus may be involved in the occurrence and development of AIT after iodine fortification. The DNA methylation level of CDH1 gene is negatively correlated with age.

Objective:To study the comparative genomic characteristics of Marmota himalayana-derived (referred to as marmota-derived) Brucella abortus (B.ab). Methods:The species and types of one strain of marmota-derived Brucella and one strain of human-derived Brucella isolated from the brucellosis epidemic area in Qinghai Province in the same year were identified. Meanwhile, DNA was extracted for whole genome sequencing and comparative genomics analysis (including phylogenetic tree construction, gene family clustering analysis, common/specific gene analysis, and genomic structural variation analysis, etc.). Results:Two Brucella strains from different hosts were identified as B.ab. By constructing a phylogenetic tree, the marmota-derived B.ab strain was grouped with strains from Heilongjiang Province and showed genetic correlation with strains from Russia. Human-derived B.ab strain was classified as a strain in Inner Mongolia Autonomous Region, Hebei Province, Beijing City, and Gansu Province. The multilocus sequence typing (MLST) of the two strains belonged to the ST2 type. Multiple locus variable-number tandem repeat analysis (MLVA) belonged to two new MLVA-8 and MLVA-11 genotypes, which were clustered in two subclusters of the same cluster and clustered with the strains from Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, and Hebei Province. The pan-genome numbers of the marmota-derived B.ab and human-derived B.ab were 283 and 8, respectively; the number of core genes (common genes) was 68 and 2, respectively; and the number of unique genes was 3 and 4, respectively. The unique gene encoded proteins were inconsistent. In marmota-derived B.ab, the main ones were the ABC transporter ATP-binding protein, N-terminal acetyltransferase, and glucose/galactose transporter. The number of homologous genes of the marmota-derived B.ab and human-derived B.ab was 16 and 20, respectively; the number of translocation and inversion genes was 13 and 8, respectively; the number of deletion mutation genes was 11 and 14, respectively. Pathogenicity analysis showed that both strains had the mprF resistance gene, and the marmota-derived B.ab strain also carried bacitracin and macrolide resistance genes. Conclusions:Brucella exhibits cross-species genetic diversity. The proteins encoded by the unique genes of the marmota-derived B.ab mainly play a role in metabolic and epigenetic regulation. The strains cluster with B.ab strains from northern China, providing a reference for molecular epidemiology and pathogen tracing of B.ab infection.

Objective:To screen the genes of suspected Mediterranean anemia patients (thalassemia) among the Bouyei in Qianxinan Bouyei and Miao Autonomous Prefecture (referred to as Qianxinan Prefecture) and to learn about the genotype and spatial distribution of thalassemia.Methods:The study subjects were Bouyei suspected thalassemia patients who visited Qianxinan Prefecture People's Hospital from November 2020 to September 2024 ( n = 4 055). Gap polymerase chain reaction (Gap-PCR) and high-throughput sequencing were used to screen for genetic variations in thalassemia. Based on the screening data, ArcMap 10.8.2 software was used to draw a spatial distribution map of thalassemia. Results:A total of 2 467 cases of thalassemia genes were detected, with an overall detection rate of 60.84%. Among them, 1 474 cases of α-thalassemia were detected, with a detection rate of 36.35%; 757 cases of β-thalassemia were detected, with a detection rate of 18.67%; and 236 cases of αβ-combined thalassemia were detected, with a detection rate of 5.82%. The spatial distribution showed that the overall detection rate of thalassemia among Bouyei in Zhenfeng County was the highest (66.83%, 268/401), the detection rate of α-thalassemia in Xingyi City was the highest (39.20%, 305/778), the detection rate of β-thalassemia in Anlong County was the highest (23.71%, 55/232), while the detection rate of αβ-combined thalassemia in Ceheng County was the highest (7.75%, 95/1 226).Conclusions:The detection rate of suspected thalassemia genes in Bouyei patients in Qianxinan Prefecture is relatively high, with α-thalassemia being predominant, and there are significant spatial distribution differences.

AIM:To establish a cell model of visceral hypersensitivity and nerve hyperplasia in irritable bowel syndrome(IBS)by conducting an in vitro co-culture of mouse P815 mast cells and N2a nerve cells and explore its possible mechanism.METHODS:Enzyme-linked immunosorbent assay(ELISA)with three replicates was used to confirm the C48/80-induced P815 degranulation.The length of neurites was observed under bright field microscopy to determine the number of differentiated neurons,thereby selecting the concentration of retinoic acid(RA)for stimulating the differentia-tion of N2a cells,with four replicates.A co-culture system of P815 and N2a cells was established using Transwell cham-bers with four replicates.The following groups were established:N2a cells cultured alone,N2a cells co-cultured with P815 cells,N2a cells co-cultured with P815 cells plus C48/80,and N2a cells plus RA group.After co-culturing,the num-ber of differentiated N2a cells was observed under bright field.The expression of nerve growth factor(NGF),tyrosine ki-nase receptor A(TRKA),growth-associated protein-43(GAP43),neuron-specific enolase(NSE),synapsin(SYN),and postsynaptic density protein-95(PSD-95)at both protein and gene levels in N2a cells was detected using Western blot and polymerase chain reaction(PCR),with four replicates.RESULTS:The best condition for N2a differentiation was stimulation with 10 μmol/L RA for 24 hours,whereas the best condition for degranulation was stimulation of P815 cells with 20 mg/L C48/80 for 24 hours.Compared with N2a cells cultured alone,the differentiation ratio of the N2a+P815+C48/80 and N2a+RA groups was significantly increased(P<0.01),and the protein and mRNA expressions of NGF,TRKA,GAP43,NSE,SYN,and PSD-95 were significantly increased(P<0.05).CONCLUSION:Our results revealed that mast cell degranulation enhances the level of nerve hyperplasia in enteric nerve cells and promotes changes in nerve structure and function.Synaptic remodeling regulated by abnormal expression of key proteins such as NGF,TRKA,and GAP43 is involved in the nerve hyperplasia induced by mast cell degranulation.