AIM:To study the mechanism of oxy-sophoridine(OSR)in relieving neuropathic pain(NP).METHODS:The analgesic effect of OSR was observed by measuring mechanical pain sensitivity.By combining OSR with agonists and antagonists re-lated to synthesis and metabolism of gamma ami-nobutyric acid(GABA),the mechanism related to analgesic effects of OSR and GABA nervous system is studied.The expression of c-Fos immunopositive cells and the expression of c-Fos and Glutamic acid decarboxylase(Glutamic acid decarboxylase 67)in brain and spinal cord were detected by immunoflu-orescence staining.Co-expression of GAD67,GABA transporter 1(gamma-Aminobutyric acid Transport-er 1,GAT-1)immunopositive cells.RESULTS:Com-pared with Sham group,spared nerve injury(SNI)group showed increased mechanical pain sensitivi-ty,increased expression of c-Fos immunopositive cells,decreased and increased co-expression of c-Fos and GAD67 and GAT-1 immunopositive cells,re-spectively.Compared with SNI group,mechanical algesia in OSR 500 and 1 000 mg/kg groups was de-creased,algesia in OSR 250 mg/kg combined with antagonist group was decreased,and algesia in OSR 500 mg/kg combined with agonist group was increased.The co-expression of c-Fos and GAD67 immunopositive cells in the brain and spinal cord of OSR 500 mg/kg group increased,while the co-ex-pression of c-Fos and GAT-1 decreased.CONCLU-SION:OSR has a good analgesic effect on NP mice induced by SNI.The mechanism is that OSR increas-es the content of central GABA by up-regulating GABAergic neurons in brain and spinal cord.

Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

Objective To evaluate the efficacy of Yunpi Runtong Formula(composed of Haematitum,Atractylodis Macrocephalae Rhizoma,Paeoniae Radix Alba,Cinnamomi Ramulus,Ophiopogonis Radix,Angelicae Sinensis Radix,Cannabis Fructus,Aurantii Fructus Immaturus,Cimicifugae Rhizoma,Picrorhizae Rhizoma,etc.)in treating functional constipation(FC)of spleen deficiency type in children and to analyze its effects on gut microbiota,defecation patterns,and the serotonin(5-HT)signaling pathway.Methods A total of 160 children with FC of spleen deficiency type treated at Shanxi Institute of Traditional Chinese Medicine from August 2022 to August 2024 were enrolled and randomly divided into a control group and a study group,with 80 patients in each group.The control group received conventional western medicine(lactulose oral solution)treatment,while the study group received Yunpi Runtong Formula treatment in addition to the control group's treatment.Both groups underwent treatment for one month.Changes in traditional Chinese medicine(TCM)syndrome scores,defecation parameters[mean defecation time,spontaneous complete bowel movements(SCBM),Bristol Stool Form Scale(BSFS)],gastrointestinal function markers[substance P(SP),gastrin(GAS),motilin(MLT)],gut microbiota composition,and 5-HT signaling pathway components(serum 5-HT levels,5-HT3R and 5-HT4R protein expression)were analyzed.Clinical efficacy and safety were evaluated.Results(1)The intergroup comparison(by chi-square test)showed that the study group exhibited significantly higher total efficacy[95.00％(76/80)]than the control group[81.25％(65/80);P＜0.01].(2)Both groups exhibited reduced TCM syndrome scores(defecation duration,stool features,difficulty of defecation,interval of defecation,and secondary symptoms;all P＜0.05),with greater improvements in the study group(P＜0.01).(3)After treatment,both groups had shorter mean defecation time,increased SCBM,and higher BSFS scores(all P＜0.05),and the study group demonstrated superior improvements(P＜0.01).(4)Serum SP,GAS,and MLT levels increased in both groups(P＜0.05),with more pronounced elevations in the study group(P＜0.01).(5)Gut microbiota analysis revealed decreased levels of Enterococcus and Enterobacter(P＜0.05)and increased levels of Bifidobacterium and Lactobacillus(P＜0.05)in both groups,with the study group showing significantly greater modulation(P＜0.01).(6)The 5-HT pathway activation(serum 5-HT,5-HT3R/5-HT4R expression)was enhanced in both groups(P＜0.05),more markedly in the study group(P＜0.01).(7)No adverse events or abnormal liver/renal function were observed.Conclusion Yunpi Runtong Formula combined with lactulose effectively alleviates FC symptoms,improves defecation patterns,gastrointestinal function,and gut microbiota,likely via 5-HT pathway activation,with high safety.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

AIM:To study the mechanism of oxy-sophoridine(OSR)in relieving neuropathic pain(NP).METHODS:The analgesic effect of OSR was observed by measuring mechanical pain sensitivity.By combining OSR with agonists and antagonists re-lated to synthesis and metabolism of gamma ami-nobutyric acid(GABA),the mechanism related to analgesic effects of OSR and GABA nervous system is studied.The expression of c-Fos immunopositive cells and the expression of c-Fos and Glutamic acid decarboxylase(Glutamic acid decarboxylase 67)in brain and spinal cord were detected by immunoflu-orescence staining.Co-expression of GAD67,GABA transporter 1(gamma-Aminobutyric acid Transport-er 1,GAT-1)immunopositive cells.RESULTS:Com-pared with Sham group,spared nerve injury(SNI)group showed increased mechanical pain sensitivi-ty,increased expression of c-Fos immunopositive cells,decreased and increased co-expression of c-Fos and GAD67 and GAT-1 immunopositive cells,re-spectively.Compared with SNI group,mechanical algesia in OSR 500 and 1 000 mg/kg groups was de-creased,algesia in OSR 250 mg/kg combined with antagonist group was decreased,and algesia in OSR 500 mg/kg combined with agonist group was increased.The co-expression of c-Fos and GAD67 immunopositive cells in the brain and spinal cord of OSR 500 mg/kg group increased,while the co-ex-pression of c-Fos and GAT-1 decreased.CONCLU-SION:OSR has a good analgesic effect on NP mice induced by SNI.The mechanism is that OSR increas-es the content of central GABA by up-regulating GABAergic neurons in brain and spinal cord.

AIM:To investigate the effect of protein kinase C(PKC)-mammalian target of rapamycin(mTOR)pathway on the apoptosis of gastric smooth muscle cells in diabetic rats,and to explore the related mechanism.METHODS:Male and female 4-week-old specific pathogen-free Sprague-Dawley rats were randomly allocated to control,diabetes,diabetes+0.1 μmol/L phorbol 12,13-myristate acetate(PMA),diabetes+0.2 μmol/L PMA,diabetes+0.5 μmol/L PMA,diabetes+2 μmol/L bisindolylmaleimide I(GF109203X),diabetes+5 μmol/L GF109203X,and diabetes+10 μmol/L GF109203X groups(n=9).Primary rat gastric smooth muscle cells cultured in a high-glucose environment in vitro were treated with 0.1 μmol/L PMA,0.2 μmol/L PMA,0.5 μmol/L PMA,2 μmol/L GF109203X,5 μmol/L GF109203X,10 μmol/L GF109203X,or vehicle.The isolated muscle technique was used to evaluate the spontaneous contraction of gastric antral smooth muscle.The pathologic changes and apoptosis of rat gastric smooth muscle were identi-fied using HE staining and flow cytometry,respectively.The expression levels of stem cell factor(SCF),c-Kit,mTOR,phosphorylated(p)-mTOR,p70 ribosomal protein S6 kinase(p70S6K),p-p70S6K,eIF4E-binding protein 1(4E-BP1),p-4E-BP1,caspase-3,B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)in gastric smooth muscle were measured by Western blot.RESULTS:The contractility of the gastric antral smooth muscle was lower(P<0.05),gastric smooth muscle atrophy and the apoptosis rate was higher(P<0.01),and the expression of SCF,c-Kit,and p-mTOR was lower(P<0.05 or P<0.01)in the diabetes group than in the control group.There was no significant difference in the spon-taneous contraction of the gastric antral smooth muscle between the diabetes and diabetes+0.1 μmol/L PMA groups,but it was significantly greater in the diabetes+0.2 μmol/L PMA and diabetes+0.5 μmol/L PMA groups(P<0.05 or P<0.01).The phosphorylation levels of mTOR,p70S6K(T421/S424),and p70S6K(T389)were also higher in the diabetes+0.2 μmol/L PMA and diabetes+0.5 μmol/L PMA groups than in diabetes group(P<0.01).Furthermore,the phosphorylation of 4E-BP1 was higher(P<0.05)in the diabetes+0.5 μmol/L PMA group than in the diabetes group(P<0.01).There was no significant difference in the spontaneous contraction of the gastric antral smooth muscle between the diabetes and diabe-tes+2 μmol/L GF109203X groups,but it was significantly lower in the diabetes+5 μmol/L GF109203X and diabetes+10 μmol/L GF109203X groups(P<0.05 or P<0.01).The phosphorylation levels of mTOR and p70S6K(T389)were lower in the diabetes+5 μmol/L GF109203X and diabetes+10 μmol/L GF109203X groups(P<0.05),the phosphorylation of p70S6K(T421/S424)was lower in the diabetes+10 μmol/L GF109203X group(P<0.05),and the phosphorylation of 4E-BP1 was lower in the diabetes+GF109203X(2,5 and 10 μmol/L)groups(P<0.05)than in the diabetes group.Com-pared with the CK group,the apoptosis rate was high in the GF109203X-treated(2,5 and 10 μmol/L)groups(P<0.01),the expression of Bax and caspase-3 was low(P<0.05),and the expression of Bcl-2 was high in the PMA-treated(0.1,0.2 and 0.5 μmol/L)groups(P<0.05).CONCLUSION:The downregulation of the PKC-mTOR pathway in the gastric smooth muscle of diabetic rats leads to apoptosis of gastric smooth muscle cells through Bax/Bcl-2 and caspase-3 and the downregulation of SCF and c-Kit,which may play an important role in the gastric dysmotility that characterizes diabetes.

ObjectiveTo understand the current situation and hot spots of research on the treatment of constipation by traditional Chinese medicine （TCM） in China and foreign countries， and provide references and directions for future research. MethodIn this study， the data analysis software CiteSpace 5.8.R3C was used to conduct bibliometrics analysis of the relevant papers on the treatment of constipation by TCM from January 1， 2000 to December 31， 2021 in China National Knowledge Infrastructure （CNKI） and Web of Science core database. The visual display was carried out. ResultAfter retrieval， 2 133 papers were included in CNKI database and 224 papers were included in Web of Science core database. The statistical analysis showed that the overall annual publication volume in China and foreign countries was on the rise， but the publication volume in China had been declining for the past two consecutive years. The author co-occurrence analysis showed that the authors with the largest number of publications in China and foreign countries were LIU Chunqiang and CHUNGWAH CHENG， respectively. The institution co-occurrence analysis showed that the institutions with the largest number of publications in China and foreign countries were the Anorectal Department of Longhua Hospital Affiliated to Shanghai University of TCM and Beijing University of Chinese Medicine， respectively. The keyword analysis showed that research in this field in China and foreign countries mainly focused on TCM therapy， clinical research， etiology and pathogenesis， etc. ConclusionThe research on the treatment of constipation by TCM is mainly concentrated in China， but there is no closely-related scientific research team. The research in this field in China and foreign countries is still developing. With the continuous deepening of research， all research institutions should pay attention to interdisciplinary intersection， highlight technological innovation， and strive to achieve greater breakthroughs in this field.

Objective:To explore the effect of nursing based on enhanced recovery after surgery (ERAS) in the perioperative period of children with hydronephrosis who underwent robot-assisted laparoscopic pyeloplasty.Methods:From March 2020 to March 2021, convenience sampling was used to select 60 children with hydronephrosis who underwent robot-assisted laparoscopic pyeloplasty in the First Affiliated Hospital of Zhengzhou University as the research object. According to the random number table method, the children were divided into the control group and the observation group, 30 cases in each group. The control group was given routine perioperative nursing. On this basis, the observation group conducted nursing based on ERAS. The postoperative recovery and postoperative complications of the two groups were compared.Results:The time of first eating after surgery, the time of extubation of wound drainage tube after surgery, and the average hospital stay of the observation group were shorter than those of the control group, and the differences were statistically significant ( P<0.01) . The total incidence of postoperative complications in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The nursing based on ERAS can effectively reduce the incidence of postoperative complications in children with hydronephrosis after robot-assisted laparoscopic pyeloplasty, and promote the postoperative recovery of children, which is worthy of clinical promotion.

With accumulating dysregulated circular RNAs(circRNAs)in pathological processes,the regulatory functions of circRNAs,especially circRNAs as microRNA(miRNA)sponges and their interactions with RNA-binding proteins(RBPs),have been widely validated.However,the collected information on experimentally validated circRNA-disease associations is only preliminary.Therefore,an updated CircR2Disease database providing a comprehensive resource and web tool to clarify the relationships between circRNAs and diseases in diverse species is necessary.Here,we present an updated CircR2Disease v2.0 with the increased number of circRNA-disease associations and novel characteristics.CircR2Disease v2.0 provides more than 5-fold experimentally validated circRNA-disease associations compared to its previous version.This version includes 4201 entries between 3077 circRNAs and 312 disease subtypes.Secondly,the information of circRNA-miRNA,circRNA-miRNA-target,and circRNA-RBP interactions has been manually collected for various diseases.Thirdly,the gene symbols of circRNAs and disease name IDs can be linked with various nomenclature databases.Detailed descriptions such as samples and journals have also been integrated into the updated version.Thus,CircR2Disease v2.0 can serve as a platform for users to systematically investigate the roles of dysregulated circRNAs in various diseases and further explore the posttranscriptional regulatory function in diseases.Finally,we propose a computational method named circDis based on the graph convolutional network(GCN)and gradient boosting decision tree(GBDT)to illustrate the applications of the CircR2Disease v2.0 database.