ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Objective To investigate the effects of Fuzheng Quxie Prescription(mainly with the actions of supporting healthy qi and dispelling pathogens)combined with neoadjuvant chemotherapy on tumor recurrence,serum thymidine kinase 1(TK1)level and immune function in patients with triple-negative breast cancer(TNBC).Methods Eighty patients with TNBC of qi and yin deficiency type were randomly divided into a combination group and a control group,with 40 patients in each group.The control group was treated with AC-T sequential chemotherapy(Doxorubicin combined with Cyclophosphamide plus sequential Docetaxel),and the combination group was treated with Fuzheng Quxie Prescription on the basis of treatment for the control group.One course of treatment covered 21 days,and the two groups were treated for 4 consecutive courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,levels of tumor markers of carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and TK1,and T lymphocyte subset levels in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and tumor metastasis and recurrence in the two groups were compared.Results(1)After 4 courses of treatment,the total effective rate of the combination group was 87.50%(35/40),and that of the control group was 67.50%(27/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the combination group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the KPS scores were significantly increased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores and the increase of KPS scores in the combination group were significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the serum CA125,CA153 and TK1 levels of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of serum CA125,CA153 and TK1 levels in the combination group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio in the two groups were significantly increased compared with those before treatment(P＜0.05),and the CD8+ level was significantly decreased compared with that before treatment(P＜0.05).The post-treatment intergroup comparison showed that the increase of the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio as well as the decrease of the CD8+ level in the combination group was all significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The one-year follow-up showed that the tumor recurrence rate and tumor metastasis rate in the combination group were 7.50%(3/40)and 12.50%(5/40)respectively,significantly lower than 25.00%(10/40)and 35.00%(14/40)in the control group,and the differences were statistically significant when comparing between the two groups(P＜0.05).Conclusion The combination of neoadjuvant chemotherapy with Fuzheng Quxie Prescription has a better therapeutic effect on TNBC patients with qi and yin deficiency syndrome,which can effectively improve the immune function of the patients,decrease the level of serum tumor markers,improve the quality of life of the patients,and reduce the incidence of tumor recurrence and metastasis.

Oral administration is the most convenient way of drug delivery， but due to the existence of intestinal barrier， the oral bioavailability of drugs is generally low， especially for drugs with low water solubility， poor permeability and macromolecules. For decades， researchers have demonstrated that nano-delivery system is one of the most effective strategies to solve this problem， but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs. Therefore， researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs. The intestinal tract were highly expressed as a transporter for ingesting various nutrients（such as glucose， oligopeptides and bile acids）， which was an excellent target of oral drug delivery system. Its substrate were modified on the nano-delivery system， and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters. At present， more and more evidences supported the potential of transporters in the field of oral drug delivery system. Therefore， this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs， including the distribution of intestinal transporters， three strategies of transporter substrate modification， the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases， with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.

Objective:To explore the ways and methods to improve the ability of hospital ethical review and ensure the quality and efficiency of ethical review.Methods:By consulting the literature and combining the practical experience of the construction of the ethics committee and the ethical review work in the hospital, analyze the present situation of ethical review in our country, and deeply analyze the main problems existing in the work of ethical review in hospitals.Results:The quality and efficiency of ethical review can be effectively improved by implementing centralized management, optimizing work processes, establishing emergency response systems, opening green channels, optimizing the composition of committee members, strengthening ethical training and assessment, establishing emergency response systems, opening green channels, strengthening pre-review communication, establishing emergency response systems, opening green channels, strengthening formal review, increasing publicity, and improving ethical awareness.Conclusions:Clarifing the division of responsibilities and strengthen multi-department interaction can effectively improve the efficiency of ethics review. Optimizing the structure of ethics committee, strengthen the training and assessment of members, can effectively enhance the ability of ethics committee review. Unifing the list of documents, optimizing the work flow and the way of examination can effectively shorten the period of ethical examination. It is suggested that continuous ethical training and assessment should be carried out, that an information-based platform system should be used to achieve dynamic supervision, and that a certification system and assessment mechanism for ethics committees should be established at the national level, to promote the improvement of the ability of ethical review.

Objective:To observe the effects of kidney-tonifying and mind-calming acupuncture therapy on sleep,mood,sex hormone levels,and traditional Chinese medicine(TCM)symptoms in patients with perimenopausal insomnia(PMI). Methods:A total of 90 patients with PMI were randomly divided into a treatment group and a control group,with 45 cases in each group.Patients in the treatment group were treated with acupuncture at Shenshu(BL23),Taixi(KI3),Baihui(GV20),and Anmian(Extra).The control group was treated with sham acupuncture.Both groups were treated 3 times a week for 4 weeks.Pittsburgh sleep quality index(PSQI)and insomnia severity index(ISI)were used to evaluate the sleep quality of the subjects before treatment,after treatment,and 1 month after treatment(follow-up).Beck depression inventory(BDI)and Beck anxiety inventory(BAI)were used to evaluate the depression and anxiety of the subjects before treatment,after treatment,and at 1-month follow-up.The TCM symptom scale was used to evaluate the TCM symptoms of the subjects before treatment,after treatment,and 1 month after treatment.Serum levels of estradiol(E2),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were measured before and after treatment. Results:During the study,2 cases dropped out of the treatment group,and no cases dropped out of the control group.The PSQI scores of the treatment group were significantly lower after treatment and at 1-month follow-up compared with those before treatment(P<0.05),and the difference was statistically significant compared with that of the control group(P<0.05).In the control group,the PSQI score was significantly lower after treatment compared with before treatment(P<0.05),and the difference was not statistically significant at 1-month follow-up compared with before treatment(P>0.05).Compared with the pre-treatment,the ISI,BDI,BAI,and TCM symptom scale scores of the treatment group were lower after treatment and at 1-month follow-up(P<0.05),and the differences with the control group at the same time point were statistically significant(P<0.05).The differences in ISI,BDI,BAI,and TCM symptom scale scores of the control group before treatment,after treatment,and at 1-month follow-up were not statistically significant(P>0.05).After treatment,the serum E2 level in the treatment group was significantly higher than that before treatment(P<0.05),and the difference with the control group was statistically significant(P<0.05).The difference in the serum E2 level before and after treatment in the control group was not statistically significant(P>0.05).The differences in the serum FSH and LH levels between before and after treatment were not statistically significant in either group of subjects(P>0.05). Conclusion:Kidney-tonifying and mind-calming acupuncture therapy can improve sleep quality,relieve anxiety and depression,delay the decrease of serum E2 level,and improve related TCM symptoms in patients with PMI.

ObjectiveTo provide reference for further strengthening the management of laboratory animals in Sichuan Province by reviewing and analyzing the results of parasitic and microbial quality inspections of laboratory animals from 2017 to 2023. Methods Sichuan Province has 31 licensed laboratory animal production units, with the main species including mice, rats, guinea pigs, rabbits, dogs, monkeys, and pigs. Sampling inspections and reports were conducted for units with laboratory animal production qualifications in accordance with current national and local standards for laboratory animal classification. The quality inspection results for various laboratory animals in Sichuan Province from 2017 to 2023 were analyzed. Results With the exception of 2018, annual quality inspections of laboratory animals were conducted every year between 2017 and 2023. Mice: In 2017, positive results for helminths, flagellates, Salmonella, murine hepatitis virus antibodies, and murine pneumonia virus antibodies were detected, with a pass rate of only 42.9%. In 2019, Staphylococcus aureus and Klebsiella pneumoniae were detected, with a pass rate of 86.7%. In 2021, Sendai virus antibodies were detected, yielding a pass rate of 85.7%.The pass rate in 2020, 2022, and 2023 was 100%. Rats: In 2017, positive results were found for helminths, mycoplasma antibodies, Staphylococcus aureus, Sendai virus antibodies, murine pneumonia virus antibodies, rat parvovirus RV strain antibodies, rat parvovirus (H-1) strain antibodies, and rat coronavirus antibodies, with a pass rate of 40.0%. In 2019, mycoplasma antibodies, Staphylococcus aureus and Klebsiella pneumoniae were detected, with a pass rate of 35.0%. No positive indicators were detected in 2020. In 2021, Sendai virus antibodies and rat parvovirus RV strain antibodies were detected, with a pass rate of 50.0%. In 2022, positive results for rat parvovirus RV strain antibodies were found, yielding a pass rate of 87.5%. In 2023, Pasteurella pneumotropica and Klebsiella pneumoniae were detected, with a pass rate of 85.7%. Dogs: In 2017 and 2019, the antibody titers for rabies virus and canine distemper virus were below the required standard, with pass rates of 33.3% and 20.0%, respectively. In 2020 and 2022, the pass rate was 100%. Guinea pigs (general grade): In 2019, positive results for Toxoplasma antibodies were detected, with a pass rate of 80.0%. In all other years, the pass rate was 100%. Monkeys: In 2019, positive results for Toxoplasma gondii and rhesus herpesvirus type I antibodies were found, with a pass rate of 87.5%.In 2020 and 2022, rhesus herpesvirus type I antibodies were positively detected, yielding pass rates of 93.3% and 97.5%, respectively. The pass rates in 2021 and 2023 were 100%. Clean guinea pigs, rabbits and pigs all passed the inspection each year. ConclusionIssues related to the parasitic and microbial quality of laboratory animals persist in Sichuan Province. Supervision and sampling inspections have proven to be effective in identifying these issues promptly, serving as a critical measure to ensure the quality of laboratory animals. The results of these inspections offer valuable data to support the healthy development of the laboratory animal industry in Sichuan Province.

ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

Objective To evaluate the pharmacokinetics(PK)of tenofovir alafenamide Fumarate tablets(25 mg)in healthy Chinese subjects after single oral administration to provide a basis for bioequivalence evaluation.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design under fasting condition,while three-way crossover design under fed condition,42 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test product(T)or reference product(R)25 mg.Plasma concentration of tenofovir alafenamide and tenofovir were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by WinNonlin software(8.1 version)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The test product and the reference product under fasting study,the main PK parameters of tenofovir alafenamide were as follows:Cmax were(215.17±94.24)and(199.30±71.11)ng·mL-1;AUC0-t were(135.44±71.60)and(123.91±53.82)h·ng·mL-1;the main PK parameters of tenofovir were as follows:Cmax were(7.30±2.27)and(7.12±1.74)ng·mL-1,AUC0-t of tenofovir were(237.16±47.09)and(230.06±43.41)h·ng·mL-1,respectively.The test product and the reference product under fed study,the main PK parameters of tenofovir were as follows:Cmax were(197.69±82.19)and(197.10±110.54)ng·mL-1;AUC0-t were(197.69±82.19)and(197.10±110.54)h·ng·mL-1;the main PK parameters of tenofovir were as follows:CMax were(2.57±1.37)and(2.58±1.31)ng·mL-1;AUC0-t were(227.08±74.33)and(238.51±128.30)h·ng·mL-1,respectively.The 90％confidence interval for geometric mean ratio of Cmax,AUC0-tof T and R under fed condition were between 80.00％-125.00％,respectively.The incidence of adverse events in fasting and fed tests was 21.43％and 30.95％,respectively,and no serious adverse event was reported.Conclusion The test formulation and reference formulation of tenofovir alafenamide fumarate tablets were equivalent and was safe.

【Objective】 To compare the diagnostic performance of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB) enhanced magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) in detecting liver metastases from metastatic colorectal cancer (mCRC). 【Methods】 We made a retrospective collection of 128 patients diagnosed with mCRC from May 2019 to June 2022 at Haikou Hospital, Xiangya School of Medicine, Central South University and Xijing Hospital, Air Force Military Medical University. All patients underwent Gd-EOB MRI and MDCT imaging. Three radiologists judged the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the two modalities for colorectal liver metastases, respectively. 【Results】 Of the 128 patients diagnosed with mCRC, a total of 462 lesions were obtained, with 424 positive and 38 negative metastases confirmed by pathology. In the interpretation of physician A, Gd-EOB MRI judged 404 positive and 38 negative liver metastases, with accuracy of 95.67%, sensitivity of 95.28%, specificity of 100.00%, a positive predictive value of 100%, and a negative predictive value of 65.52%. MDCT judged 337 positive and 37 negative liver metastases, with accuracy of 80.95%, sensitivity of 79.48% and specificity of 97.37%, a positive predictive value of 99.70%, and a negative predictive value of 29.84%. In the interpretation of physician B, Gd-EOB MRI judged 403 positive and 36 negative liver metastases, with accuracy of 95.02%, sensitivity of 95.05%, specificity of 94.74%, a positive predictive value of 99.51%, and a negative predictive value of 64.91%. MDCT judged 335 positive and 35 negative liver metastases, with accuracy of 80.09%, sensitivity of 79.01%, specificity of 92.11%, a positive predictive value of 99.11%, and a negative predictive value of 28.23%. In the interpretation of physician C, Gd-EOB MRI judged 406 positive and 38 negative liver metastases, with accuracy of 96.10%, sensitivity of 95.75%, specificity of 100.00%, a positive predictive value of 100.00%, and a negative predictive value of 67.86%. MDCT judged 352 positive and 34 negative liver metastases, with accuracy of 83.55%, sensitivity of 83.02%, specificity of 89.47%, a positive predictive value of 98.88%, and a negative predictive value of 32.08%. Gd-EOB MRI judged the nature of liver metastases with higher accuracy, sensitivity and negative predictive value than MDCT, and had better agreement with pathological examination results in the judgment of physician A and physician C (Kappa=0.770, 0.788). In physician B’s judgment, the agreement with pathological findings was fair (Kappa=0.731), while the agreement between the results of MDCT examination and pathological findings was poor (Kappa=0.379, 0.378 and 0.400). 【Conclusion】 Gd-EOB MRI has higher accuracy, sensitivity and positive predictive rate than MDCT in diagnosing colorectal liver metastasis, and has higher diagnostic performance. Therefore, it can provide more valuable reference information for clinical differential diagnosis. Subcapsular lesions, peribiliary metastases and hepatic steatosis can reduce the diagnostic performance of MDCT, while Gd-EOB MRI detection can provide more accurate results than MDCT.