Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

Objective:To explore the current situation of binary coping in patients with perimenopausal syndrome and analyze its influencing factors, in order to provide a basis for improving the level of binary coping.Methods:Using convenience sampling method, a total of 210 patients with perimenopausal syndrome and their spouses from the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine were cross-sectional surveyed by a general data questionnaire, the Binary Coping Scale, and the Modified Kupperman Score Scale. The influencing factors of binary coping level in patients with perimenopausal syndrome were explored by univariate analysis and variance decomposition model analysis.Results:A total of 200 valid questionnaires were retrieved.The patients aged (50.52 ± 2.89) years old. The binary coping score was (79.64 ± 22.74) points. The variance decomposition model analysis showed that marriage age, type of medical insurance, number of children, education level, family monthly income, spouse′s education level, presence of major comorbidities in spouse, modified Kupperman score, presence of generalized anxiety in spouse were the main influencing factors of binary coping in patients with perimenopausal syndrome (all P<0.05). Conclusions:The binary coping scores of patients with perimenopausal syndrome are lower than normal, and considering the influence and involvement of patients' spouses, nursing staff should pay special attention to patients who are married relatively early, have more children, have lower education levels, and have lower family monthly incomes. Additionally, attention should be given to spouses who experience widespread anxiety, have a lower level of education, and suffer from major chronic diseases. By developing and implementing comprehensive intervention measures aimed at improving the Kupperman score and the level of binary coping, both parties can be encouraged to support each other more effectively, thereby improving the marital relationships of patients during the perimenopausal period.

Objective:To use the best evidence of noninvasive mechanical ventilation related pressure injury prevention in the clinic guided by integrated promoting action on research implementation in health services framework (i-PARIHS) and evaluate its effect.Methods:This study is an unsynchronized before and after control study. Convenience sampling method was used to select patients receiving non-invasive mechanical ventilation from 7 wards of Beijing Hospital from October 2019 to September 2021. A total of 575 patients receiving non-invasive mechanical ventilation from October 2019 to September 2020 were included in the control group and 602 patients from October 2020 to September 2021 were included in the trial group. The control group adopted the usual care measures, and the trial group applied the prevention program for noninvasive ventilation related facial pressure injuries. The incidence of pressure injury was compared between the two groups. Nurses in 7 wards were investigated before and after the intervention program to compare the changes of knowledge level.Results:In the control group, there were 354 males, 221 females, aged (77.13 ± 14.49) years old; in the trial group there were 392 males, 210 females, aged (75.60 ± 14.27) years old. The incidence of pressure injury in the trial group was lower than the control group, but showed no significant difference ( P>0.05). In the control group, 11 cases suffered pressure injury, including 5 cases in stage 2, 6 cases in stage 3 and above. There were 9 cases in the trial group, including 8 in stage 2 and 1 in stage 3 and above. The severity of pressure injury in the trial group was lower than that in the control group, and the difference was significant ( χ2 = 3.83, 4.11, both P<0.05). The scores of the nurse′pressure injury knowledge increased from (6.77 ± 1.53) points to (7.15 ± 1.47) points, with a significant difference ( t = -2.31, P<0.05). Conclusions:Management of the prevention of noninvasive mechanical ventilation related facial pressure injury through evidence-based practice can reduce its incidence, reduce its severity, and it is beneficial to improve the clinical nurses' prevention knowledge and clinical practice level of facial pressure injury related to non-invasive mechanical ventilation.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease （NAFLD） in mice. METHODS The male ApoE－/－ mice were randomly divided into the model group and Hirudo low- dose and high-dose groups （0.45， 0.9 g/kg）， with 10 mice in each group； another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically， once a day， for 8 consecutive weeks. In the 13th week， the body weight and liver weight of mice in each group were measured after the last medication， and the liver index was calculated； the serum levels of nuclear factor-κB （NF-κB）， tumor necrosis factor-α （TNF- α）， interleukin-1β （IL-1β）， IL-6， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were detected； the liver pathomorphological changes were observed； the protein expressions of peroxisome proliferator-activated receptor γ（PPARγ） and silence information regulator type 1 （SIRT1） were detected. RESULTS Compared with the control group， the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells， with significant lipid accumulation； the body weight， liver weight and liver index of the mice， and serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C significantly increased， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased （P＜0.01）. Compared with the model group， the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups； the body weight， liver weight and liver index， the serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C decreased significantly， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1， thus having a significant ameliorative effect on NAFLD.

Objective To investigate the efficacy and safety of tyrosine kinase inhibitor(TKI)combined with immune checkpoint inhibitor as the second-line therapy for advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the clinical data of 63 patients with advanced HCC who were admitted to Department of Interventional Radiology,The First Affiliated Hospital of Soochow University,from January 2018 to December 2022,and all patients experienced progression/intolerance after transcatheter arterial chemoembolization combined with first-line TKI and were switched to second-line TKI with or without immune checkpoint inhibitor.The 32 patients receiving second-line TKI with immune checkpoint inhibitor were enrolled as combination group,and the 31 patients receiving second-line TKI alone were enrolled as single treatment group.Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response,and Common Terminology Criteria for Adverse Events 5.0 was used to evaluate adverse events.The Kaplan-Meier method was used to calculate median overall survival(mOS)and median progression-free survival(mPFS)for the two groups,and the two groups were compared in terms of objective response rate(ORR)and disease control rate(DCR).The chi-square test was used for comparison of baseline data and follow-up results between groups.Results The median follow-up time was 16.5(3.2-53.4)months for the 63 patients.The combination group had an mOS of 24.3(95%confidence interval[CI]:20.0-28.6)months and an mPFS of 9.8(95%CI:7.5-12.1)months,while the single treatment group had an mOS of 15.8(95%CI:11.4-20.1)months and an mPFS of 4.1(95%CI:3.2-4.9)months,and there were significant differences in mOS and mPFS between the two groups(P=0.029 and 0.038).The combination group had an ORR of 47%and a DCR of 84%,while the single treatment group had an ORR of 19%and a DCR of 65%;there was a significant difference in ORR between the two groups(P=0.021),but with no significant difference in DCR between the two groups(P=0.070).As for adverse events,4 patients(12.5%)in the combination group and 3(10.0%)in the single treatment group experienced grade Ⅲ-Ⅳ serious adverse events,with no fatal drug reactions in either group,and there was no significant difference in the incidence rate of adverse events between the two groups(P=0.783).Conclusion Compared with TKI alone,TKI combined with immune checkpoint inhibitor has a more significant therapeutic effect as the second-line therapy for advanced HCC,without increasing serious adverse reactions.

Objective To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis(UC).Methods UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract,and their targets were screened using public databases for construction of the core protein-protein interaction(PPI)network and GO and KEGG enrichment analyses.Forty male C57 mice were randomized into normal control group,model group,mesalazine group and Cynanchum wilfordii group(n=10),and in the latter 3 groups,mouse UC models were established by treatment with 2.5%DSS and the latter 2 groups drug interventions by gavage.The therapeutic effect was evaluated by recording body weight changes and DAI score.Pathological changes of the colon tissue were observed with HE and AB-PAS staining,and JAK2 and STAT3 protein expressions were detected with Western blotting.The metabolites and metabolic pathways were identified by metabonomics analysis.Results We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts,including 19 steroids.A total of 177 Cynanchum wilfordii targets,5406 UC genes,and 117 intersection genes were obtained.JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways.Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice(P<0.05),alleviated intestinal pathologies,and decreased JAK2 and STAT3 protein expressions in the colon tissues.Most of the 83 intersecting differential metabolites between the control,model and Cynanchum wilfordii groups were identified as glycerophospholipids,arachidonic acid,and amino acids involving glycerophospholipid metabolism and other pathways.Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites.Conclusion Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.

Objective:To investigate the relationship between sarcopenia and the long-term prognosis of elderly patients with locally advanced colorectal cancer.Methods:A retrospective analysis was conducted on clinical data from 205 elderly colorectal cancer patients aged 70 years and above who underwent radical resection with TNM staging of stage Ⅱ to Ⅲ at Beijing Hospital between January 2014 and December 2018.The study utilized abdominal CT scans taken within 30 days before surgery to measure the skeletal muscle area(SMA)of the 3rd lumbar vertebrae cross-section.Sarcopenia was defined as a skeletal muscle index(SMI) of ≤52.4 cm 2/m 2 in men and ≤38.5 cm 2/m 2 in women(SMI=SMA/height 2).A comparison was made between the clinical and pathological conditions of patients with and without sarcopenia in the two groups, with an analysis of the impact of sarcopenia on the long-term prognosis of elderly postoperative colorectal cancer patients. Results:Among the 205 patients assessed, 63.4%(130/205)were diagnosed with sarcopenia.The group with sarcopenia had a higher percentage of individuals aged 80 years and older( χ2=6.420, P=0.011)compared to those without sarcopenia.Additionally, this group had a lower proportion of overweight or obese patients( χ2=9.366, P=0.009), fewer patients who underwent adjuvant chemotherapy, and a lower 5-year disease-free survival rate post-surgery( χ2=6.257, 7.347, P=0.012, 0.007).Kaplan-Meier analysis indicated that disease-free survival rate was better in elderly patients with locally advanced colorectal cancer who did not have sarcopenia compared to those with sarcopenia(Log-rank χ2=6.919, P=0.009).Moreover, in elderly patients without sarcopenia, those who received adjuvant chemotherapy had a more favorable disease-free survival outcome than those who did not receive such treatment(Log-rank χ2=4.745, P=0.029).Multifactorial Cox regression analysis showed that TNM stage Ⅲ( HR=1.634, 95% CI: 1.110-2.404, P=0.013)and the presence of sarcopenia( HR=1.509, 95% CI: 1.017-2.238, P=0.041)were significant factors influencing the poor long-term prognosis of elderly patients with locally advanced colorectal cancer. Conclusions:Sarcopenia is associated with aging and body mass index, and has been found to be a significant factor in the long-term prognosis of elderly colorectal cancer patients.Those with sarcopenia tend to have a poorer prognosis, while those without may experience benefits from adjuvant chemotherapy.

Objective To conduct a detailed clinical phenotypic analysis and gene mutation detection on an au-tosomal dominant Van der Hoeve syndrome family,and to identify the pathogenic gene mutation sites of the family and the impact of the mutation on gene coding.Methods Clinical data including medical history,physical examina-tion and auxiliary examination were collected and peripheral blood samples were collected from the Van der Hoeve syndrome families.Exome sequencing and Sanger sequencing were performed on 22 family members.The data were analyzed using bioinformatics software.Results The family had a total of 5 generations,with each generation expe-riencing consecutive illnesses.Each generation of men and women could suffer from the disease,which conformed to the characteristics of autosomal dominant inheritance.The 12 patients in this family were all born with blue sclera and short stature.8 patients had a history of fractures and could heal normally.3 patients were considering hearing loss caused by Van der Hoeve syndrome.12 patients had a base deletion(c.1128delT)in exon 17 of the COL1A1 gene,causing a change in the amino acid coding after position 376 and ending the amino acid coding prematurely at position 539.10 asymptomatic individuals in this family didn't had this mutation.Conclusion The patient of this family was identified as Van der Hoeve syndrome caused by c.1128 delT mutation.