Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans ; Parkinson Disease/microbiology* ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology*

Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective:To investigate the risk factors of brain metastases in patients with limited-stage small cell lung cancer (SCLC) undergoing preventive brain radiotherapy after remission and to construct prediction model.Methods:A total of 231 patients with limited-stage SCLC who received chemoradiotherapy and achieved remission in 3201 Hospital from January 2015 to January 2023 were selected as the study objects. Logistic regression was used to analyze the influencing factors on the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. Binary logistic regression was used to construct a prediction model. Receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy of each indicator and the prediction model on the occurrence of brain metastases in patients.Results:The median follow-up time of the whole group was 73 months, and 42 cases of brain metastases occurred, with an incidence rate of 18.18%. There were statistically significant differences in the incidence of brain metastases among patients with different T stage ( Z=-4.97, P<0.001), clinical stage ( Z=-8.17, P<0.001), and time from initial treatment to thoracic radiotherapy ( χ2=21.38, P<0.001). Multivariate analysis showed that T stage (stage T 3: OR=6.29, 95% CI: 1.58-25.06, P=0.009; stage T 4: OR=12.91, 95% CI: 3.74-44.57, P<0.001), clinical stage (stageⅡ, OR=8.75, 95% CI: 2.89-26.51, P<0.001; stage Ⅲ, OR=18.43, 95% CI: 7.24-46.92, P<0.001), and time from initial treatment to thoracic radiotherapy ( OR=0.25, 95% CI: 0.11-0.56, P=0.001) were independent influencing factors on the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. The diagnostic prediction model based on the above indicators was logit ( P) =-19.91+1.84× stage T 3 +2.56× stage T 4+2.17× stage Ⅱ+2.91× stage Ⅲ-1.38× time from initial treatment to thoracic radiotherapy. ROC curve analysis showed that the area under the curve of T stage, clinical stage, time from initial treatment to thoracic radiotherapy, and the diagnostic prediction model for predicting the occurrence of brain metastasis after remission in patients with limited-stage SCLC who received preventive brain radiotherapy were 0.728, 0.660, 0.687, and 0.846, respectively, and the area under the curve of the diagnostic prediction model was significantly larger than those of the other indicators (all P<0.05) . Conclusion:T stage, clinical stage and the time from initial treatment to thoracic radiotherapy are all influential factors for the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. The diagnostic prediction model based on the above indicators can help to guide clinicians to accurately screen patients at high risk of brain metastases in the early stage.

Objective:To investigate the changes of mortality，causes of death，and cause-specific mortality rate（CMR）of hospitalized neonates in NICU of the First Affiliated Hospital of Sun Yat-sen University.Method:A retrospective study was performed to compare the mortality，cause of death，and CMR of hospitalized neonates in period Ⅰ（2005-2009），period Ⅱ（2010-2014）and period Ⅲ（2015-2020）.Result:The overall mortality of hospitalized neonates in NICU of our hospital was 0.51%（104/20 493）through 2005 to 2020. The mortality in period Ⅰ，Ⅱ and Ⅲ were 0.61%（48/7 855），0.43%（27/6 209），and 0.45%（29/6 429），respectively. Compared with period Ⅰ，the mortality of preterm infants decreased significantly in period Ⅱ（3.14% vs 1.24%， χ2=14.076， P<0.01）and in period Ⅲ（3.14% vs 0.90%， χ2=25.157， P<0.01）. Eighty-five（81.7%）neonates were premature，and ninety-one（89.2%）neonates had definite abnormal perinatal factors. The CMR of hospitalized neonates related to pulmonary hemorrhage，congenital anomalies，and NRDS were 1.22‰（25/20 493），0.93‰（19/20 493），and 0.59‰（12/20 493），respectively. The CMR of other causes were sepsis 0.44‰（9/20 493），extremely premature 0.34‰（7/20 493），and perinatal asphyxia 0.24‰（5/20 493），respectively. Compared with period Ⅰ，specific mortality of NRDS in period Ⅱ（1.27‰ vs 0.16‰， χ2=5.487， P=0.016）and period Ⅲ（1.27‰ vs 0.16‰， χ2=5.738， P=0.014）significantly decreased. The leading causes of neonatal death in period Ⅰ，period Ⅱ，and period Ⅲ were NRDS，pulmonary hemorrhage，and congenital anomalies，respectively.And 71.2%（74/104）of neonatal deaths occurred within 7 days after birth. Conclusion:The mortality of preterm infants and specific mortality of NRDS in NICU have significantly decreased over the past 16 years.Congenital anomalies and infections remain important causes of death，and further efforts are needed to improve perinatal care.

Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.

There are millions of patients with taxane-induced peripheral neuropathy （TIPN）， and there is no effective treatment or prevention measure in clinical practice. The occurrence of TIPN may be related to the dosage form of paclitaxel drugs， genetic and molecular markers， drug dosage and chemotherapy cycle， patient factors， etc. At present， drugs for treating TIPN mainly include those that inhibit axonal degeneration （such as dosazosin， tamsulosin）， prevent mitochondrial dysfunction （such as glutathione trisulfides， antioxidants α -lipoic acid）， improve calcium imbalance in the internal environment （Shaoyao gancao decoction， N-type voltage-gated calcium channel inhibitor IPPQ）， and inhibit neuroinflammation （such as chemokine inhibitors and selective interleukin-8 receptor inhibitors DF2726A）. Further exploration of drug treatment strategies targeting different induction mechanisms is expected to become a new direction for precise clinical prevention and personalized treatment of TIPN.

Objective To systematically explore the traditional Chinese medicine(TCM)common symptoms,syndrome elements,clinical syndrome differentiation,and medication rules of coronary microvascular disease(CMVD),and to provide a reference for quantitative criteria of clinical differentiation of CMVD,specification of the diagnosis and efficacy evaluation of TCM clinical syndrome,and guidance of clinical medication.Methods The databases including CNKI,Wanfang,VIP,and SinoMed were searched for research papers on the treatment of CMVD by TCM published from database inception to May 16,2023.Relevant information of the included literature was extracted and the database was established.Then,the frequency statistics of symptoms,syndrome elements,syndrome types and Chinese medicinals were carried out.Latent structural models were constructed using Latern 5.0 and Rstudio softwares respectively for comprehensive clustering and association rule analysis,so as to explore the symptom characteristics,syndrome elements distribution,common syndromes and medication rules for TCM treatment of CMVD.Results A total of 107 literature were included,involving 36 syndromes,17 syndrome elements,121 symptoms and 143 Chinese medicinals.It was speculated that the main syndrome element of CMVD was blood stasis,followed by qi deficiency,qi stagnation,phlegm turbidity,yin deficiency and yang deficiency.The main type of syndrome was qi deficiency and blood stasis,followed by heart blood stasis obstruction,qi stagnation and blood stasis,phlegm blended with stasis,qi-yin deficiency,etc..The main medicinals were Chuanxiong Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Angelica Sinensis Radix and Astragali Radix.The medicinals used in the treatment of CMVD were classified as blood-activating and stasis-resolving drugs,deficiency-tonifying drugs,qi-regulating drugs in terms of their efficacy.Conclusion The location of CMVD is in heart,and related to liver and kidney.The syndrome of CMVD is deficiency in origin and excess in superficiality.Blood stasis runs through the development of the disease.The treatment is mainly to activate blood circulation and remove stasis,activate meridians and relieve pain,which should be supplemented with the therapies of tonifying and invigorating qi,soothing the liver and regulating qi,dispelling phlegm and dissipating masses according to the patients'syndromes.

AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.

Brucellosis is a zoonotic infectious disease caused by Brucella infection. So far, animal to animal Brucellosis has not been eradicated, and there is a lack of safe and effective human vaccine. Therefore, "early, combined, sufficient, and full course" drug treatment remains an important strategy in the management of human Brucellosis. The goal of treating brucellosis is to alleviate and shorten the symptom period, reduce complications, relapses, and chronicity. At present, although antibiotic treatment is effective for most patients, there are still some patients who experience treatment failure or later recurrence, so the treatment strategy for brucellosis urgently needs to be optimized. This article elaborates on the treatment principles, clinical treatment status, and future development trends of brucellosis, in order to provide references for optimizing drug treatment methods for brucellosis.