BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

BACKGROUND:Endometrial receptivity is a key factor in embryo implantation in northwest Tibetan cashmere goats,and the expression of genes related to endometrial receptivity and their variable splicing are still unclear. OBJECTIVE:To analyze and explore genes and variable splicing events related to endometrial receptivity in northwest Tibetan cashmere goats. METHODS:On days 5 and 15 of pregnancy(representing pre receptive endometrium group and receptive endometrium group),three northwest Tibetan cashmere goats were randomly selected.Endometrial tissue was collected and stained with hematoxylin and eosin to observe tissue morphology.Immunohistochemical staining was used to detect the expression of endometrial receptive marker proteins leukemia inhibitory factor and vascular endothelial growth factor.After the total RNA was extracted and the quality test was qualified,transcriptome sequencing was performed to search differentially expressed mRNAs,lncRNAs,circRNAs,and miRNAs,perform functional prediction,and analyze alternative splicing mRNAs and lncRNAs related to endometrial receptivity. RESULTS AND CONCLUSION:(1)Compared with the pre receptive endometrium group,the expression levels of leukemia inhibitory factor and vascular endothelial growth factor proteins in the endometrial tissue of the receptive endometrium group were significantly increased.(2)The sequencing results showed that the differentially expressed genes were mostly mRNA and lncRNA genes,including 250 upregulated mRNAs,193 upregulated lncRNAs,135 downregulated mRNAs,and 123 downregulated lncRNAs,which were significantly enriched in the Wnt,Hedgehog,and Hippo signaling pathways.(3)Alternative splicing event analysis uncovered 8 differentially expressed variable splicing transcripts,which were all mRNA transcripts,including 2 downregulated and 6 upregulated,and were significantly associated with vascular endothelial growth factor receptor signaling,cell motility,and embryonic development.

BACKGROUND:The causal relationship between modifiable factors such as lifestyle,metabolic characteristics,and nutritional intake and joint sports injuries has been increasingly recognized in clinical studies.However,the exact causal relationship between these modifiable factors and joint sports injuries remains unclear. OBJECTIVE:To investigate the causal relationship between modifiable factors and joint sports injuries using Mendelian randomization to provide a basis for sports injury prevention. METHODS:The GWAS dataset of intervening factors and joint sports injuries was obtained from publicly available data.The causal relationships between lifestyle,metabolic characteristics,nutritional intake,and joint sports injuries were explored using the inverse variance weighting method,the MR-Egger method,and the weighted median method.For sensitivity analyses,Cochran's Q test,MR-Egger regression,leave-one-out method,and MR-PRESSO were used to verify the stability and reliability of the results. RESULTS AND CONCLUSION:(1)In terms of lifestyle,coffee(OR=0.29,95%CI:0.10-0.79,P=0.016),and tea consumption(OR=0.41,95%CI=0.19-0.85,P=0.017)were associated with a decreased risk of ankle and foot joint sports injuries,and coffee consumption(OR=3.31,95%CI=1.02-10.73,P=0.046)was potentially causally associated with an increased risk of shoulder joint sports injuries;and never smoking(OR=0.78,95%CI=0.70-0.87,P=1.49×10-5)was significantly causally associated with a decreased risk of ankle and foot joint sports injuries.(2)In terms of metabolic characteristics,calcium levels(OR=0.88,95%CI=0.79-0.98,P=0.017)were potentially causally associated with a decreased risk of wrist and hand joint sports injuries.(3)In terms of nutritional intake,vitamin A intake(OR=1.08,95%CI:1.02-1.13,P=0.007)was potentially causally associated with increased risk of knee joint sports injury.(4)For the sensitivity analysis,Cochran's Q test showed the existence of heterogeneity(P<0.05),so the random effect model was used for the analysis.MR-Egger regression and MR-PRESSO test did not find evidence of pleiotropy(P>0.05),and the leave-one-out method showed that the results were stable after eliminating single nucleotide polymorphisms one by one.(5)This study preliminarily reveals the effects of modifiable factors,such as lifestyle,metabolic characteristics,and nutritional intake,on the risk of joint sports injuries.It provides valuable research evidence and guidance for the prevention of joint sports injuries.

Houpo Qiwutang originated from the Synopsis of the Golden Chamber， and it consists of seven medicines： Magnoliae Officinalis Cortex， Rhei Radix et Rhizoma， Aurantii Fructus Immaturus， Cinnamomi Ramulus， Zingiberis Rhizoma Recens， Glycyrrhizae Radix et Rhizoma， and Jujubae Fructus. It is a basic formula for the treatment of abdominal fullness. Through the bibliometric method， the historical history， drug base， preparation and dosage， decoction method， and ancient and modern applications of Houpu Qiwu Tang were analyzed by means of textual research. The research finds that Houpu Qiwu Tang has been passed down through the generations in an orderly manner with fewer changes. The drug base of this formula is basically clear， and the base of Magnoliae Officinalis Cortex， Rhei Radix et Rhizoma， Cinnamomi Ramulus， Zingiberis Rhizoma Recens， and Jujubae Fructus is consistent with the 2020 edition of Chinese Pharmacopoeia. The mainstream base of Aurantii Fructus Immaturus is the dried young fruit of Citrus aurantium of Rutaceae family， and the historical mainstream base of Glycyrrhizae Radix et Rhizoma is the dried root of Glycyrrhiza uralensis of Leguminosae family. The modern dosage of this formula is 110.40 g of Magnoliae Officinalis Cortex， 41.40 g of Rhei Radix et Rhizoma， 69 g of Aurantii Fructus Immaturus， 27.60 g of Cinnamomi Ramulus， 69 g of Zingiberis Rhizoma Recens， 41.40 g of Glycyrrhizae Radix et Rhizoma， and 30 g of Jujubae Fructus. In addition， the decoction method is to add 2 000 mL of water with the above seven flavors of the medicine， boil it to 800 mL， and then take 160 mL in a warm state each time. The amount of the medicine taken for each time is 22.08 g of Magnoliae Officinalis Cortex， 8.28 g of Rhei Radix et Rhizoma， 13.80 g of Aurantii Fructus Immaturus， 5.52 g of Cinnamomi Ramulus， 13.80 g of Zingiberis Rhizoma Recens， 8.28 g of Glycyrrhizae Radix et Rhizoma， and 6 g of Jujubae Fructus. The modern application of this formula involves the digestive system， respiratory system， and urinary system. It is more advantageous in digestive system diseases such as early postoperative inflammatory bowel obstruction， functional dyspepsia， gastric pain， functional abdominal distension， and gastric reflux esophagitis. By comprehensively examining the key information of Houpu Qiwu Tang， this paper aims to provide literature support for the development and clinical application of this formula.

Systemic inflammatory response (SIR) evoked by cardiopulmonary bypass (CPB) is still one of the major causes of postoperative multiple organs injuries. Since the concentrations of circulating inflammatory factors are positively associated with postoperative adverse events, removal or inhibition of inflammatory factors are considered as effective treatments to improve outcomes. After more than 20 years of research, however, the results are disappointed as neither neutralization nor removal of circulating inflammatory factors could reduce adverse events. Therefore, the role of circulating inflammatory factors in CPB-related organs injuries should be reconsidered in order to find effective therapies. Here we reviewed the association between circulating inflammatory factors and the outcomes, as well as the current therapies, including antibody and hemadsorption. Most importantly, the role of circulating inflammatory factors in SIR was reviewed, which may be helpful to develop new measures to prevent and treat CPB-related organs injuries.

Pancreaticobiliary maljunction （PBM） is a rare congenital developmental defect of the biliary-pancreatic system characterized by a junction of the pancreatic and bile ducts outside the duodenal wall， forming an extended common channel. This anatomical anomaly compromises the normal function of Oddi’s sphincter， weakens defenses against reflux， and thus triggers a series of biliary and pancreatic complications. Although there is a relatively low incidence rate of PBM， its insidious clinical symptoms often lead to delayed diagnosis， which increases the difficulties in treatment and the risk of poor prognosis. For PBM patients with marked bile duct dilatation， surgical intervention， especially cholecystectomy combined with extrahepatic bile duct resection and bile duct-jejunum Roux-en-Y anastomosis， remains the standard treatment at present. For PBM without marked bile duct dilatation， there are still controversies over related treatment strategies， and most experts are in favor of cholecystectomy， while there is still a lack of consensus on the management of extrahepatic bile ducts， which requires further research and exploration. Endoscopic retrograde cholangiopancreatography （ERCP） is currently the gold standard for diagnosing PBM and assessing pancreaticobiliary abnormalities， and it can not only clarify the nature of lesion， but also collect the bile and biliary duct tissue for pathological examination. ERCP also has the function of interventional treatment， such as stenting， expansion， and drainage， thereby bringing benefits to patients comorbid with biliary neoplasms. However， the application of ERCP in screening is limited by its invasiveness， with increases in technique complexity and the risk of complications in the pediatric population. This article summarizes the definition， classification， pathogenesis， and epidemiological features of PBM and the research advances in current diagnosis and treatment strategies， in order to provide guidance for clinical practice.

Objective To investigate the discovery and disposal process and epidemiological characteristics of the first confirmed case of mpox (formerly named monkeypox) in Huai'an, Jiangsu Province, and to provide reference for the prevention and control of key infectious diseases in this region. Methods The on-site epidemiological investigation data of the first confirmed case of mpox on June 21, 2023, as well as the results of nucleic acid detection and gene sequencing of laboratory specimens were analyzed retrospectively. Possible sources of infection were explored. Results The first confirmed case of mpox was an AIDS patient, men who had sex with men (MSM), who had no history of travel abroad or outside the city within 21 days before the onset of the disease, but had interacted with some people outside the city, and the epidemiological trajectory was complex. The detection of mpox virus nucleic acid was positive (BioGerm reagent: Ct value 21.8, ZhuoCheng reagent: Ct value 21.2). According to genetic sequencing, the first confirmed case was classified as C.1.1 lineage of clade IIb. During the investigation on the source of infection of the first confirmed case, one new asymptomatic infected person was found. Based on the epidemiological investigation and laboratory results, the first confirmed case was believed to be caused by local infection, however, the source of infection was unclear. Although there was an epidemiological association with asymptomatic infected people, the direct evidence of mutual infection was insufficient, and it could not be ruled out that there was still a hidden transmission chain between regions. The source of infection of the asymptomatic infected person was presumed to be the first confirmed case or an unidentified person with whom he had high-risk sex and caused anal bleeding. Conclusion The first confirmed case is caused by local infection. Awareness of case diagnosis and reporting in medical institutions should be improved, and publicity and education should be provided to key exposed populations, especially those men who have sex with men, to prevent the occurrence of large-scale local epidemic.

ObjectiveTo explore the effect of exercise on anxiety and depression in cancer patients during chemotherapy, as well as the optimal exercise dosage. MethodsA PICO framework was constructed, and randomized controlled trials (RCTs) on the effect of exercise on anxiety and depression in cancer patients during chemotherapy were retrieved from databases of PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang data, from the establishment to November, 2023. The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database (PEDro) scale. Data were synthesized and analyzed using RevMan 5.3, and the risk of bias was evaluated using Stata 18.0. ResultsA total of 13 RCTs involving 1 340 subjects were included. The scores of PEDro scale were five to eight. Exercise interventions significantly improved anxiety (SMD = -0.70, 95%CI -1.18 to -0.22, P = 0.004) and depression (SMD = -0.89, 95%CI -1.43 to -0.34, P = 0.002) compared to the control group. Subgroup analyses showed that, the exercise effect on anxiety was less than 45 minutes a time (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), more than three times a week (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), and less than twelve weeks (SMD = -0.21, 95%CI -0.36 to -0.07, P = 0.005). For depression, it was less than 45 minutes a time (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), more than three times a week (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), and less than twelve weeks (SMD = -0.52, 95%CI -0.92 to -0.13, P = 0.01). Moderate to high-intensity exercise interventions significantly outperformed the control group in improving anxiety (SMD = -0.21, 95%CI -0.37 to -0.06, P = 0.007) and depression (SMD = -0.21, 95%CI -0.41 to -0.01, P = 0.04). ConclusionExercise interventions can effectively improve anxiety and depression in cancer patients during chemotherapy, and it suggests for high-intensity exercise, less than 45 minutes a time, more than three times a week, and less than twelve weeks.