5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT3R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+ and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT3Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT3Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and the γ-aminobutyric acid(GABA)"disinhibition"mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT3R-induced GABA"disinhibition"mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs.However,given the circuit specific modulation of 5-HT3Rs on emotion,systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT3R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Objective To explore the core acupoints and compatibility rules of acupuncture and moxibustion for epilepsy by using complex network method. Methods A prescription database was established through inclusion and exclusion criteria for searching literatures for databases from China National Knowledge Infrastructure, VIP, Wanfang, Web of Science, EMBASE, and Pubmed. SPSS Modeler software was used to analyze the frequency and correlation of acupoints, and Gephi0.10.1 software was used to establish a complex network model to explore the core acupoints and acupoint selection rules of prescriptions for epilepsy. Results Ultimately, 144 valid literatures were included, 199 prescriptions were extracted, involving 102 acupoints. Baihui acupoint had the highest frequency of use, specific acupoints were mainly Five-shu acupoint, the Eight Meridian Intersection acupoint, and the Back-shu acupoint. In selection of meridians, most acupoints were selected from governor meridian. Association rule analysis showed that Baihui-Taichong had the highest level of support and confidence. The analysis of complex network topology showed that 36 acupoints such as Baihui, Dazhui, Yaoqi and Fenglong were the core acupoints in the treatment of epilepsy by acupuncture and moxibustion. The analysis of acupoint communities revealed three major acupoint groups including governor meridian passing through treatment group, far and near matching acupoint group of the four limbs and head, and differentiation group of Zang-fu and body fluid for epilepsy treatment. Conclusion Acupoint compatibility of epilepsy by acupuncture and moxibustion should be mainly based on principle of the governor meridian combined with the differentiation of viscera and body fluid, and attention should be paid to distal-proximal point association.

Objective:To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes.Methods:Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios ( RRs) and their 95% confidence intervals ( CIs) between baseline RC level and incident DR. Results:The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR ( RR=1.40, 95% CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times ( RR=5.59, 95% CI 1.51-20.73). Conclusion:The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.

OBJECTIVE To observe the efficacy and safety of ticagrelor combined with Compound xueshuantong capsules in the treatment of unstable angina pectoris. METHODS Totally 120 patients with unstable angina pectoris with deficiency of Qi and Yin combined admitted to Sanmenxia Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were randomly divided into clopidogrel group （group A）， ticagrelor group （group B） and combined medication group （group C）， with 40 patients in each group. In addition to conventional treatment， group A was given clopidogrel orally； group B was given ticagrelor orally； group C was given ticagrelor and Compound xueshuantong capsule orally. After 12 weeks of treatment， the clinical efficacy， frequency of angina attacks， coagulation function indicators， cardiac function indicators， traditional Chinese medicine syndrome efficacy， and the incidence of adverse cardiovascular events and bleeding incidence were evaluated in the 3 groups. RESULTS The total effective rates of group A， group B and group C were 77.5%， 85.0% and 90.0%， respectively. The incidence of adverse cardiovascular events and bleeding events were 7.5%， 7.5% and 5.0% in the respective groups， with no statistically significant difference （P＞0.05）. The frequency of angina attacks， duration of angina attacks and duration of dyspnea were significantly reduced or shortened in all 3 groups after treatment compared to before treatment （P＜0.05）. The frequency of angina attacks in group C was significantly lower than that in groups A and B after treatment （P＜0.05）. The levels of fibrinogen （FBG） and D-dimer in all 3 groups were significantly lower after treatment compared to before treatment （P＜0.05）； group A had significantly higher levels of FBG and D-dimer compared to group B and C （P＜0.05）. The left ventricular end-diastolic diameter and left ventricular end-systolic diameter in all three groups were significantly shorter after treatment， and the left ventricular ejection fraction was significantly higher compared to before treatment （P＜0.05）， but there were no statistically significant differences among those groups （P＞0.05）. The total effective rates of traditional Chinese medicine syndrome efficacy in groups A， B and C were 67.5%， 80.0% and 87.5%， respectively， with group C being significantly higher than group A （P＜0.05）. CONCLUSIONS In addition to conventional treatment， ticagrelor combined with Compound xueguantong capsules can more significantly reduce the frequency of angina attacks in patients with unstable angina pectoris， reduce the levels of FBG and D- dimer， improve traditional Chinese medicine syndrome efficacy， and do not increase the risk of bleeding.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Retinal pigment epithelium(RPE)has essential functions,such as nourishing and sup-porting the neural retina,and is of vital importance in the pathogenesis of age-related retinal degen-eration.However,the exact molecular changes of RPE during aging remain poorly understood.Here,we isolated human primary RPE(hRPE)cells from 18 eye donors distributed over a wide age range(10-67 years old).A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins.Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells.The results of proteomic data analysis and verifications suggest that RNF123-and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage dur-ing aging.In older hRPE cells,apoptotic signaling-related pathways were up-regulated,and endo-plasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes.Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Objective:To investigate the characteristics and differences of anxiety, depression and sleep disorder among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Guangzhou, then optimize the antiretroviral therapy and provide effective mental intervention.Methods:All HIV/AIDS patients from the outpatient department of Guangzhou Eighth People's Hospital were enrolled in the present study from January 2016 to December 2016. They were evaluated by the hospital anxiety and depression scale and Pittsburgh Sleep Quality Index, to analyze the levels of depression, anxiety and sleep disorder.Results:The incidences of anxiety, depression and sleep disorder were 30.5%(61/200), 31.0%(62/200) and 22.5%(45/200) respectively. 36.1%(22/61) of patients with anxiety and 35.5%(22/62) of patients with depression were accompanied by sleep disorder. The sleep disturbance index were significant higher in HIV/AIDS patients with anxiety ( t=4.065, P<0.001) or depression ( t=3.034, P=0.003) than those without anxiety or depression. Anxiety was mainly found in HIV/AIDS patients in aged 20 to 40 group ( F=7.998, P=0.018), while depression was mostly found in HIV/AIDS patients who didn't receive higher education ( F=13.55, P=0.001), and sleep disorder was more common in people with CD4 + count <200 cells/μl ( t=2.01, P=0.046). Conclusions:Anxiety and depression, which could aggravate sleep disorder, are very common in HIV/AIDS patients. Psychological care need to be strengthened to HIV positive patients in early phase, and screening questionnaires should be conducted before antiretroviral treatment began.

Objective:It is yet to be clarified whether pylorus-preserving gastrectomy (PPG) for early gastric cancer will bring the risk of radical tumor resection, whether it will increase the incidence of postoperative complications, and how much is the benefit of the quality of life for patients after surgery, these issues are not clear. This meta-analysis aims to evaluate the efficacy and safety of pylorus-preserving gastrectomy (PPG) for early middle gastric cancer.Methods:The Chinese and English literatures about PPG and distal gastrectomy (DG) for early gastric cancer were searched from PubMed, Embase, The Cochrane Library, Web of Science, CNKI net and Wanfang database. Literature inclusion criteria: (1) Prospective or retrospective cohort study of PPG and DG for early middle-third gastric cancer published publicly; (2) Patients with early middle-third gastric cancer; (3) The enrolled literatures include at least one of the following outcome indicators: the efficacy indicators include gallstone, residual gastritis, bile reflux, delayed gastric emptying, dumping syndrome, reflux esophagitis and overall complication; the long-term prognostic indicators include 5-year survival rate and 5-year tumor recurrence. Literature exclusion criteria: (1) Reviews, case reports, conference summaries and other non-control studies; (2) Repeated published studies, incomplete studies and unextractable studies; (3) The depth of tumor invasion exceeding submucosa. The search time ended in July 2020. The basic information and evaluation indicators included in the article were extracted. The retrospective study was evaluated using Newcastle-Ottawa literature quality evaluation scale. The prospective randomized controlled study was evaluated using Jadad modified scale. Meta-analysis was performed using Review Manager 5.3. Publication bias was assessed using funnel map. Publication bias was tested using Egger tools.Results:A total of 717 literatures were retrieved, and 17 literatures were enrolled finally, including 2 randomized controlled trials and 15 retrospective studies. A total of 2427 patients were enrolled, including 948 in PPG group and 1479 in DG group. The meta-analysis of the efficacy indicators showed that there were significant differences in gallstones incidence (OR=0.42, 95% CI: 0.28-0.65, P<0.001), residual gastritis incidence (OR=0.50, 95% CI: 0.32-0.77, P=0.002), bile reflux incidence (OR=0.30, 95% CI: 0.20-0.45, P<0.001), delayed gastric emptying incidence (OR=2.40, 95% CI:1.67-3.45, P<0.001), and postoperative dumping syndrome incidence (OR=0.28, 95% CI: 0.15-0.51, P<0.001), while there were no significant differences in postoperative overall complications (OR=0.97, 95% CI: 0.69-1.35, P=0.840), reflux esophagitis incidence (OR=0.79, 95% CI: 0.39-1.61, P=0.520) between the two groups. The meta-analysis of the long-term prognostic indicators showed that no significant differences of 5-year survival (OR=1.02, 95% CI: 0.61-1.71, P=0.940) or 5-year tumor recurrence (OR=0.77, 95% CI: 0.36-1.68, P=0.520) were observed between the two groups. Conclusion:The incidences of gallstone, residual gastritis, dumping syndrome, bile reflux are lower after PPG in early gastric cancer, while the postoperative overall complications and long-term survival are comparable between PPG and DG, indicating that PPG is quite safe and feasible.