Astragaloside Ⅳ （AS-Ⅳ） is a natural triterpenoid saponin compound derived from Astragalus membranaceus and has shown significant potential in the regulation of liver diseases. This article reviews the latest research advances in AS-Ⅳ in the field of liver diseases in China and globally， and it is found that AS-Ⅳ exerts a liver-protecting effect by regulating lipid metabolism， exerting an anti-tumor/anti-inflammatory/anti-fibrotic effect， and modulating gut microbiota. Its mechanism of action involves multiple signaling pathways， such as AMPK， NLRP3， NF-κB， JAK2/STAT3， and Nrf2. These research findings provide a scientific basis for the development of liver-protecting drugs or functional foods based on the natural product AS-Ⅳ.

Objective:To analyze the association of CD19+CD24hiCD27+regulatory B cells(Bregs)with ankylosing spondylitis(AS).Methods:Eighty patients with AS in Ganzhou People's Hospital from January 2019 to December 2021 were enrolled as observa-tion group,meantime,another 60 healthy individuals were set as control group.Observation group was further divided into subgroups according to clinical stages and disease activity,advanced stage,ankylosis stage,active stage and non-active stage.Percentage of CD19+CD24hiCD27+Bregs in CD19+cells in peripheral blood of observation group and control group,and observation group patients with different stages were detected and compared,thereafter,relationship between percentage of CD19+CD24hiCD27+Bregs and clini-cal characteristics of AS patients were discussed,such as course of disease,duration of morning stiffness,the Bath Ankylosing Spon-dylitis Disease Activity Index(BASDAI),IL-10,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)and X-ray classifi-cation of sacroiliitis.Results:Percentage of CD19+CD24hiCD27+Bregs in peripheral blood in observation group was higher than that in control group.Percentage of CD19+CD24hiCD27+Bregs in CD19+cells in AS patients at ankylosis stage was higher than that in patients at advanced stage,and percentage of CD19+CD24hiCD27+Bregs in peripheral blood of patients with bony ankylosis stage was higher than that in patients with fibrous ankylosis stage.Percentage of CD19+CD24hiCD27+Breg in CD19+B cells in active AS patients was sig-nificantly higher than that of patients with stable AS(P<0.05).Serum IL-10 level in observation group was lower than that in control group,while ESR and CRP levels were higher than those in control group,with statistical significance(P<0.05).Percentage of CD19+CD24hiCD27+Breg in CD19+B cells in peripheral blood of AS patients was positively correlated with BASDAI score and serum IL-10 level,while negatively correlated with ESR and CRP levels,and had no correlation with morning stiffness time and X-ray classi-fication of sacroiliitis.Conclusion:Percentage of CD19+CD24hiCD27+Bregs in peripheral blood is reduced in AS patients,moreover,percentage is closely related to disease stage,activity and laboratory indicators IL-10,ESR and CRP,which may be involved in the occurrence and development of AS.

Objective:To elucidate the quasispecies variation of 3′ half-length genome in HIV-1 CRF103_01B-infected patients in Beijing using single genome amplification (SGA).Methods:This study enrolled six CRF103_01B-infected patients who were diagnosed during a drug resistance monitoring for newly diagnosed cases or newly treated cases with antiviral therapy in Beijing from 2017 to 2020. RNA was extracted from their plasma samples, and 3′ end of cDNA was diluted by serial dilution method after reverse transcription. Nested PCR was used to amplify the 3′ half-length genome sequences of HIV-1 quasispecies. MEGA 11 was used to construct Neighbor-Joining (NJ) tree and calculate the intrahost genetic distance. Genetic variation in HIV-1 quasispecies was visualized by online Highlighter tool. BootScan analysis was performed using Simplot 3.5 software to analyze inter-quasispecies recombination. Virus tropism was predicted by online Geno2pheno tool.Results:Among the six CRF103_01B-infected patients, five were men who have sex with men. A total of 144 3′ half-length genome SGA sequences (19-36 sequences/case) were obtained. The NJ tree based on the 3′ half-length genome of HIV-1 quasispecies revealed different degrees of genetic diversity. The HIV-1 quasispecies in BL4748-00 case of acute infection has the least variation with the intrahost distance of 0.002±0.000, showing genetic homogeneity. The quasispecies sequences from BL4981-00, BL3150-00 and BL3558-00 cases formed at least three subclusters, respectively, with different evolutionary directions, and their intrahost distance ranked from 0.031±0.004 to 0.016±0.002 (BL3150-00>BL3558-00>BL4981-00). The quasispecies sequences from the couple BL3022-00 (female) and BL3023-00 clustered into a large monophyletic cluster (bootstrap value=100%), and the intrahost distance of the latter (0.025±0.003) was higher than that of the former (0.019±0.002). Inter-quasispecies recombination was observed in BL3558-00 case. The quasispecies from the six patients were CCR5-tropic viruses.Conclusions:The diversity of quasispecies variation in CRF103_01B-infected patients is related to disease progress. Genetic homogeneity is observed in acute HIV infection, while multiple evolutionary directions are detected in chronic infection. Co-infection or superinfection cases are not found, but there are recombination events among quasispecies in some cases.

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Objective To investigate the effects of different ratios of ω-3 polyunsaturated fatty acids(ω-3 PUFA)on depression and cognitive impairment in patients with major depression.Methods A randomized,double-blinded controlled trial was used to randomly assign patients with depression to a cognitive improvement group,a depression improvement group,and a placebo group.The cognitive improvement group took 1388 mg of docosahexaenoic acid(DHA)and 692 mg of eicosapentaenoic acid(EPA)every day and the depression improvement group took 1248 mg of EPA and 832 mg of DHA every day.The placebo group took the same dose of soybean oil for 12 weeks,during which psychiatric medication was maintained.The 24-item Hamilton depression scale(HAMD-24)was used to evaluate depressive symptoms,and the standardized MATRICS consensus cognitive battery(MCCB)was used to evaluate cognitive function after 6 weeks and 12 weeks,respectively.Results The study recruited a total of 46 patients with depression including 22 in the cognitive improvement group,12 in the depression improvement group,and 12 in the placebo group.After 6 weeks of treatment,the HAMD-24 scores were significantly lower in the depression improvement group(19.00±10.70)and cognitive improvement group(16.58±9.39)than in the placebo group(31.10±10.03)(P<0.01).After 12 weeks of treatment,HAMD-24 scores were significantly lower in the depression improvement group(13.58±8.43)than in the placebo group(28.10±15.04)(P=0.02).No significant interaction effect was found on the cognitive assessment scores in any dimension after 6 weeks and 12 weeks of treatment(P>0.05).The incidence rate of adverse events in the depression improvement group was 16.7%(2/12),and no adverse events were reported in the other two groups.There was no significant difference in the incidence of adverse events among the three groups(P=0.13).Conclusion Treatment with ω-3PUFA for 6 weeks can improve the depressive symptoms of patients with depression.The formula with a higher ratio of EPA exhibits higher effectiveness while the two groups of ω-3PUFA formulas with different ratios do not improve cognitive function.

Objective:To evaluate the efficacy and tolerability of the dual therapy of dolutegravir (DTG) plus lamivudine (3TC) as a switch simplified strategy in treatment-experienced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients.Methods:Treatment-experienced HIV/AIDS patients who switched to a dual therapy containing DTG (50 mg, once daily) plus 3TC (300 mg, once daily) were included in Beijing You′an Hospital, Capital Medical University from September 2016 to May 2019. HIV RNA, CD4 + T lymphocyte count, blood lipid indexes, renal function indexes were collected when patients changed the treatment regimen (baseline) and after 48 weeks of treatment. Efficacy (HIV RNA<50 copies/mL) and safety of the dual therapy were analyzed. Statistical comparisons were performed using the Wilcoxon matched-pairs signed rank test. Results:The reasons for 33 patients switching the treatment regimen were virologic failure (four cases, 12.1%), simplification of regimen (11 cases, 33.3%), and drug toxicity (18 cases, 54.5%). The patients were treated with anti-retroviral therapy (ART) for 2.13 (1.05, 4.23) years before regimens switching. Twenty-nine (87.9%) patients were virologically suppressed at baseline, and four (12.1%) patients were virological failure. After switching to DTG plus 3TC, all 33 patients showed HIV RNA<50 copies/mL after 48 weeks of treatment. The baseline CD4 + T lymphocyte count was 543 (363, 595)/μL. After switching the treatment regimens for 48 weeks, CD4 + T lymphocyte count was significantly increased to 625 (455, 651)/μL, and the difference was statistically significant ( Z=3.14, P=0.002). Compared with baseline, low-density lipoprotein-cholesterol was increased after 48 weeks of treatment (2.35(1.80, 3.08) mmol/L vs 3.12(2.74, 3.87) mmol/L), while triglyceride (2.21(1.27, 4.37) mmol/L vs 1.61(1.20, 2.22) mmol/L), the ratio of total cholesterol to high-density lipoprotein-cholesterol (5.02 (4.13, 6.40) vs 4.70 (3.55, 5.35)) and estimated glomerular filtration rate (106.4(78.2, 118.2) mL/(min·1.73 m 2) vs 88.6 (75.7, 107.9) mL/(min·1.73 m 2)) were decreased. The differences were all statistically significant ( Z=4.89, 2.37, 2.09 and 2.83, respectively, all P<0.050). No patient discontinued due to adverse events. Conclusions:The use of dual therapy containing DTG and 3TC is effective and well-tolerated in treatment-experienced HIV/AIDS patients under any prior ART without significant adverse events.

γδ T cells are a unique type of natural immune cells that recognize antigens without the limitation of the major histocompatibility complex (MHC). They are of great significance in anti-infection immunity, serving as the important defense for maintaining immune homeostasis. Human immunodeficiency virus (HIV) infection induces the imbalance of γδ T cell subsets. A long-term antiretroviral therapy (ART) significantly damages the number and function of γδ T cells, eventually result ing in disease progression and immune reconstitution of HIV-infected patients. In the present study, we aimed to review the phenotypic function of γδ T cells, the biological role of γδ T cells in HIV infection, and γδ T cell-based immunotherapy.

Objective:To analyze the characteristics of HIV-1 molecular network in men who have sex with men (MSM) from 2016 to 2018 in Kunming, Yunnan province, explore the risk factors associated with HIV-1 transmission network and provide evidence for the effective implementation of intervention.Methods:A total of 540 samples of newly reported HIV-1 positive MSM were consecutively collected in Kunming from 2016 to 2018, the pol gene fragments were amplified by nested polymerase chain reaction (PCR). HIV-1 molecular networks were constructed according to the bootstrap value of the maximum likelihood evolutionary tree over 95% and the genetic distance less than 3%. The factors associated with the subjects entering network and network growth were further analyzed. Results:Among 459 successfully sequenced samples, seven genotypes were found, in which CRF07_BC (49.2%, 226/459) and CRF01_AE (40.3%, 185/459 ) were predominant. Other genotypes included URFs (4.8%, 22/459), CRF08_BC (3.1%, 14/459), CRF55_01B (1.7%, 8/459), B (0.7%, 3/459) and CRF68_01B (0.2%, 1/459). A total of 163 sequences entered the network, with an entry rate of 35.5%(163/459), forming 56 clusters with the number of individuals in the cluster was between 2 and 13. The analysis of the factors associated with entering network showed that the MSM who married and had multiple homosexual partners were more likely to be found in HIV-1 molecular networks. Multivariate logistic regression analysis showed that the number of sexual partners was the factor for the growth of HIV-1 molecular network. According to the criteria for the emergence of three or more newly reported cases in every year, six transmission clusters were judged as active transmission clusters, in which MSM who were not Kunming natives, had sexually transmitted diseases (STD), were divorced and students were the key targets of intervention.Conclusions:HIV-1 genotypes in MSM in Kunming were becoming complex, the risk factors associated with transmission networks in MSM in Kunming included being married and having multiple partners, the intervention targets in active transmission clusters included MSM who were not Kunming natives, had STD, were divorced and students. This study provided the basis for applying HIV-1 molecular networks to real-time intervention in this population.

Objective To investigate the application of time‐resolved fluorescence immunoassay (TRFIA) in the detection of specific antibody of syphilis .Methods Specific antibody of syphilis was detected in serum samples of 240 cases of syphilis and 150 healthy subjects by TRFIA ,Treponemal pallidum particle agglutination(TPPA) and Treponemal pallidum enzyme linked immu‐nosorbent assay(TP‐ELISA) .The sensitivity ,specificity and positivity of these three methods were compared .Results The sensi‐tivity of TRFIA ,TP‐ELISA ,TPPA were 100 .00% ,98 .75% and 97 .92% ,without significantly differences(P>0 .05) ,and the spe‐cificity were 99 .33% ,98 .67% and 100 .00% .The false positive rate of TRFIA was 0 .67% ,and the false negative rate was 0 .00% . The false positive rate of TP‐ELISA was 1 .33% ,and the false negative rate was 1 .25% .False positive rate and false negative rate of TRFIA were lower than TP‐ELISA(P<0 .05) .Conclusion TRFIA could be with high sensitivity and specificity in syphilis spe‐cific antibody test ,and could be used for routine screening of syphilis specific antibody .

OBJECTIVE: To investigate the clinical efficacy of self-made 32P applicator for treating different kinds of keloid. others were treated with surgical excision combined with self-made 32P applicator. The 32P applicator was shaped according to the size and shape of the diseased region and the application time was calculated according to the dose rate and the decay correction. 4.0-5.0 Gy was applied in every diseased region in each of the four days (one course), and 4-6 courses in total was required, with 4 weeks of intervals following each course. For children, dose was reduced to 4 Gy or less once a day in every diseased region. Patients in the operation combined with application group were performed keloids excision first. Then 32P applicators were applied to the wound without any exudation in the same way as above. RESULTS: Of all the 39 patients (lesion thickness≤0.3 cm, 32P applicator therapy only), 32 ones was cured (82.1%), with the total effective rate of 98%. For patients with lesion thickness > 0.3 cm, the total effective rate of 32P applicator therapy and surgical excision combined with self-made 32P applicator were 55.6% and 93.3% respectively, and the difference was ofsignificance (P < 0.01 ). Among these patients, those with disease course less than 9 months had the effective rates of 25.0% and75.0% corresponding to 32P applicator therapy only and surgical excision combined with self-made 32p applicator respectively.For those with long course of disease, the effective rates were 13% and 77% respectively. A total of 26 patients experienced local buming and slight pain during the 32P applicator treatment, and all the symptoms were relieved by using calamine lotion; 5 patients and 2 patients expedencad grade Ⅰ and Ⅱ radio dermatitis respectively, which were relieved by using Mupirocin Ointment. No radio dermatitis of grade Ⅲ or above occurred to any patient. In addition, pigmentation or color changing occurred at local skins of cured patients.CONCLUSION: 32P applicator therapy is safe and effective for treating keloid. For patients with short disease course and lesion thickness ≤0.3 cm, 32P applicator therapy only is enough. Otherwise, patients are suggested to use 32P applicator after operation.