ObjectiveThis paper aims to study the potential active compound components and action mechanism of Shenqi Dihuangtang in the treatment of diabetic kidney disease （DKD） through network pharmacology and in vivo experimental verification. MethodsUltra-high-performance liquid chromatography-Q-exactive orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS） technology was used to clarify the main active chemical components of Shenqi Dihuangtang， and it was combined with network pharmacology methods such as gene ontology （GO） functional annotations and Kyoto encyclopedia of genes and genome （KEGG） to predict the potential action mechanism of Shenqi Dihuangtang in treating DKD. Subsequently， the DKD model of db/db male mice was established， and the mice were randomly divided into model group， low-dose Shenqi Dihuangtang group （6.10 g·kg^-1）， medium-dose Shenqi Dihuangtang group （12.19 g·kg^-1）， high-dose Shenqi Dihuangtang group （24.38 g·kg^-1）， and daplizin group （1.25 mg·kg^-1）. During the same period， C57BL/6J male mice were selected into normal group and received drug intervention for 8 weeks， respectively. During this period， the body weight and fasting blood glucose （FBG） of the mice were dynamically monitored， and oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were performed at the end of dosing. The levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， uric acid （UA）， albumin （ALB）， and total protein （TP） were measured by an automatic biochemical analyzer， and 24-hour urine protein was measured by a urine protein quantitative kit. Hematoxylin-eosin （HE）， periodic-acid Schiff （PAS）， and Masson staining were employed to observe the renal histopathology. The expression of nephrotic protein Nephrin was observed by immunohistochemistry. Western blot was used to detect the expression of epithelial-mesenchymal transition （EMT）-related proteins such as TGF-β₁， Smad2/3， α-smooth muscle actin （α-SMA）， neural-cadherin （N-Cadherin）， and snail protein. ResultsUPLC-Q-Exactive Orbitrap MS identified 384 active compounds in the aqueous extract of Shenqi Dihuangtang. According to oral bioavailability≥30% and the five drug-like principles， 44 key active ingredients were screened out， and 169 intersection targets highly correlated with DKD were matched. Among them， there was a significant interaction relationship between tumor necrosis factor（TNF）， interleukin（IL）-6， protein kinase B（Akt）1， Caspase-3， Jun proto-oncogene （JUN）， hypoxia inducible factor-1α（HIF-1α）， B cell lymphoma-2（Bcl-2）， matrix metallopeptidase-9（MMP-9）， IL-1β， and TGF-β₁. GO functional annotations were significantly enriched in cellular components such as membrane rafts， membrane microdomains， and collagen-containing extracellular matrix， molecular functions such as DNA-binding transcription factor binding， R-Smad binding， and Smad protein binding， as well as biological processes such as reactions to lipopolysaccharides（LPS）， reactions to bacteria-derived molecules， and wound healing. The KEGG pathway was significantly enriched in lipids and atherosclerosis， TGF-β signaling pathway， phosphatidylinositol 3 kinase （PI3K）/Akt signaling pathway， etc. In vivo experimental results showed that the high-dose Shenqi Dihuangtang group could significantly reduce FBG levels in db/db mice （P<0.01）， improve OGTT （P<0.01） and ITT （P<0.01） levels， reduce SCr （P<0.01）， BUN （P<0.01）， UA （P<0.01） and 24-hour BUN （P<0.01）， and increase ALB （P<0.01） and TP （P<0.01） levels. Pathological staining confirmed that the high-dose Shenqi Dihuangtang group could significantly reduce the glomerular mesangial matrix area and collagen deposition （P<0.01） and upregulate the positive expression rate of Nephrin （P<0.01）. Western blot results showed that the high-dose Shenqi Dihuangtang group significantly downregulated the expression of TGF-β₁ （P<0.01） and Smad2/3 （P<0.01） signal molecules and inhibited the protein levels of α-SMA （P<0.01）， N-Cadherin （P<0.01）， and Snail （P<0.01）. ConclusionShenqi Dihuangtang can inhibit the TGF-β₁/Smad signaling axis and block the renal EMT process， thereby improving DKD renal fibrosis damage. Further analysis of its key active components and clinical transformation pathways is needed in the future.

Objective:To evaluate the effect of non-pharmacological interventions on benefit finding of breast cancer patients by using network Meta-analysis.Methods:Randomized controlled trials on the effect of non-pharmacological interventions on the benefit finding of breast cancer patients were retrieved by computer from CNKI, VIP, Wanfang Date, China Biology Medicine disc, PubMed, Web of Science, Cochrane Library, EBSCO, Embase, Medline, Ovid, CINAHL and other databases. The retrieval time was from establishment of the databases to October 15th, 2023. Literature screening and data extraction were carried out independently by two researchers. The Cochrane Manual 5.1.0 randomised Controlled Trial Bias Risk Assessment Scale were used to evaluate the included literature. And the Stata 14.0 were used for Network Meta-analysis.Results:A total of 10 literatures were included. The results of Network Meta-analysis showed that cognitive behavior therapy was the best intervention in improving the benefit finding of breast cancer patients. The effects of different non-pharmacological intervention methods in descending order were cognitive behavior therapy, yoga, acceptance and commitment therapy, self disclosure and muscle stretching.Conclusions:Existing evidence suggests that cognitive behavioral therapy is most effective in improving benefiting finding in breast cancer patients, but more valuable evidence support and high-quality randomized controlled trial studies are needed to further validate.

Objective:To explore the clinicopathological characteristics and the related influencing factors of efficacy and prognosis of elderly patients with malignant mesothelioma(MM)in Chinese population.Methods:We retrospectively analyzed the clinical data of 115 patients aged 65 years and above who were diagnosed with MM in Beijing Hospital, Peking University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences between November 2007 and July 2024, and the patients were grouped according to age(≥75 years in the older group and <75 years in the younger group), histological types and therapy regimens.Kaplan-Meier curve and Log-rank test were performed.Cox regression was used in prognostic analysis.Results:The positive expression rate of Calretinin in the Chinese elderly population with MM was consistent with previous reports, while the positive rates of Cytokeratin 5/6(CK5/6), WT-1, and D2-40 were much lower.The overall response ratio(ORR)for first-line treatment was 17.3%(9/52), and the disease control rate(DCR)was 92.3%(48/52).The ORR for second-line treatment was 7.7%(1/13)and the DCR was 76.9%(10/13).The ORR and DCR were higher in the first-line immunotherapy group than in the chemotherapy group, 50.0% vs.14.6%( P=0.134)and 100.0% vs.91.6%( P=1.000), respectively.The ORR in the second-line immunotherapy group was higher than that in the chemotherapy group, 25.0% vs.0, respectively, and the DCR were both 75.0% in two groups.The median progression free survival(mPFS)was 9.2 months and median overall survival(mOS)was 19.0 months for patients receiving first-line treatment, and the mPFS was 3.3 months and mOS was 11.0 months for second-line therapy.The first-line immunotherapy provided more shorter mPFS(1.6 months vs.9.2 months, P=0.081)and longer mOS(not reached vs.18.1 months, P=0.147)than the chemotherapy group.The younger group had prolonged mPFS(9.7 months vs.7.2 months, P=0.305)while shorter mOS(18.1 months vs.23.9 months, P=0.289)compared with the older group, and none of them reached statistical differences.Both mPFS and mOS were prolonged in the epithelioid subtype compared with the non-epithelioid subtypes, 10.4 months vs.1.6 months( P<0.001)and 20.3 months vs.4.6 months( P=0.803), respectively.Both mPFS(7.1 months vs.4.7 months, P=0.583)and mOS(18.3 months vs.6.3 months, P=0.134)were prolonged in the second-line chemotherapy group compared with the immunotherapy group.The Cox regression analysis showed that gender, Eastern Cooperative Oncology Group, Performance Status(ECOG PS)and positive CK5/6 were both the independent predictors for the first-line PFS.Histological type was an independent prognostic factor for the first-line OS. Conclusions:MM in the Chinese elderly population exhibits unique clinicopathologic characteristics.The immunotherapy improves ORR, DCR and prolongs mOS in first-line use, and improves ORR in second-line.First-line treatment improves mPFS in the younger group compared with the older group.Multivariate Cox regression demonstrates that gender, ECOG PS and CK5/6 expression are both predictors of efficacy, and histological type is an independent prognostic factor for survival of the Chinese elderly population with MM.

Objective:To understand the incidence of sleep disorder in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients before antiviral therapy, and to explore its risk factors.Methods:200 newly treated HIV/AIDS patients who visited the Eighth Affiliated City Hospital of Guangzhou Medical University from January to June 2016 were randomly selected. According to the Pittsburgh Sleep Quality Index (PSQI), they were divided into a good sleep group and a Sleep disorder group; The influencing factors of sleep disorder in HIV/AIDS patients were analyzed by univariate analysis and multivariate logistic regression.Results:The incidence of Sleep disorder in 200 HIV/AIDS patients before antiviral therapy was 22.5%(45/200); CD4 + T cell count was (414.13±202.16)/μl; 29%(58/200) of patients had CD4 + T cell counts<200/μl. There were significant differences in CD4 + T cell count and the proportion of patients with syphilis infection, comorbidity anxiety and comorbidity depression between the good sleep group and the Sleep disorder group (all P<0.05). Multivariate logistic regression analysis showed that syphilis infection ( OR=4.606; 95% CI: 1.973-10.752; P<0.001), comorbidity anxiety ( OR=2.496; 95% CI: 1.086-5.737; P=0.031) and comorbidity depression ( OR=2.087; 95% CI: 0.915-4.760; P=0.040) were risk factors for sleep disorder in HIV/AIDS patients before antiviral treatment. Conclusions:The incidence of Sleep disorder in HIV/AIDS patients before antiviral therapy in Guangzhou is high, especially in patients with syphilis infection, comorbidity anxiety and comorbidity depression. The sleep disorder of HIV/AIDS patients should be assessed and detected early, and multiple interventions should be taken to improve sleep quality.

Background::Chronic liver disease has emerged as a leading cause of non-acquired immune deficiency syndrome (AIDS)-related mortality in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients. The relationship between CD4 cell count and HIV-related opportunistic infections and tumors has been well characterized; however, it is unclear whether CD4 cell count is associated with HCV-related hepatic events.Methods::This observational cohort study enrolled HCV/HIV-coinfected patients from the National Free Antiretroviral Treatment Program of China from 2004 to 2019 in Guangzhou. The primary outcome was a composite of hepatic events, including cirrhosis complications, hepatocellular carcinoma (HCC), and liver-related mortality. Kaplan-Meier survival and multivariate logistic regression analyses were performed.Results::Among the 793 patients, 43 developed hepatic events during a median follow-up of 6.7 years, including 35 cirrhosis complications, 13 HCC cases, and 14 cases of liver-related mortality. The 5-year and 10-year cumulative incidences of hepatic events were 4.2% and 9.3%, respectively. Patients who developed hepatic events had a less satisfactory increase in CD4 cell count, lower peak CD4 (354.5 cells/μL vs. 560.0 cells/μL, P < 0.001), and lower percentage of peak CD4 > 500 cells/μL (30.2% vs. 60.7%, P < 0.001) after the initiation of antiretroviral therapy (ART) than those who did not. The cumulative incidences of hepatic events were higher in patients with lower peak CD4 levels with adjusted odds ratios of 3.96 (95% confidence interval [CI]: 1.51-10.40), 2.25 (95% CI: 0.87-5.86), and 0.98 (95% CI: 0.35-2.74) for patients with peak CD4 at <200 cells/μL, 200-350 cells/μL, and 351 to 500 cells/μL, respectively, relative to those with peak CD4 > 500 cells/μL. Peak CD4 was negatively associated with the risk of hepatic events in a dose-response manner ( P-value for trend = 0.004). Conclusion::Persistently low CD4 cell counts after ART are independently associated with a high risk of hepatic events in HCV/HIV-coinfected patients, highlighting the important role of immune reconstitution in improving liver outcomes.

Objective: To investigate the clinical, immunological and virological characteristics of HIV-1 infected patients in the acute phase, for the sake of improving the diagnosis of acute infection with HIV-1. Methods: We retrospectively analyzed the clinical manifestation and laboratory data of patients with acute HIV-1 infection who were admitted to the Center of Infectious Diseases, Guangzhou Eighth People’s Hospital from January 2012 to June 2017. Results: Forty-four patients were enrolled into the study, 86.4% of them were male. 59.1% patients were homosexually transmitted. Clinical symptoms and signs mostly consisted of fever (84.1%), lymphadenopathy (56.8%) and so on, while 15.9% patients had central nervous system symptoms. Most common opportunistic infection included lung infection (50.0%) and oropharyngeal candidiasis (22.7%). Leucopenia (10 patients, 22.7%), and decreased CD4⁺ T cell count (267.5 cells/μl), inverted CD4⁺ /CD8⁺ ratio (86.4%) was mostly seen. Compared to patients who had HIV RNA load less than 6 lg copies/ml, the group of patients who had HIV RNA load more than 6 lg copies/ml had lower levels of CD4⁺ T cells (t=-3.724, P=0.001). Conclusions Patients with acute HIV infection have many different kinds of clinical symptoms and can be accompanied by opportunistic infection, and with high viremia.

Objective To investigate the liver histological characteristics of children with chronic hepatitis B (CHB).Methods We recruited data of children with CHB and liver biopsy,then analyzed their liver histopathological characteristics and their associations with laboratory parameters.Results One hundred and twenty-four children with CHB were included in the present study,including 114 (91.9％) HBeAg-positive CHB children and 10 (8.1％) HBeAg-negative CHB children.In HBeAg-positive CHB children,the frequency of significant necroinflammation stratified by ALT levels was 32.1％ (9/28) in ALT ≤ULN,60.7％ (17/28) in ALT(1-2) ×ULN and 81.0％ (47/58) in ALT＞2 ×ULN group,while significant fibrosis was 46.4％ (13/28) in ALT ≤ ULN,71.4％ (20/28) in ALT (1-2) × ULN and 74.1％ (43/58) in ALT ＞ 2 × ULN group,respectively.Significant liver histological abnormalities were much higher in the ALT ＞ 2 × ULN and ALT (1-2) × ULN groups than the ALT ≤ ULN group.Logistic analysis indicated only AST levels associated with significant inflammation (OR =1.032,P =0.008) and significant fibrosis (OR =1.026,P =0.007).Conclusion Frequencies of significant liver histological abnormalities in children with CHB are high,and AST levels are associated with them.

Objective To evaluate the therapeutic effect of highly active anti-retroviral therapy (HAART) in treatment-na(i)ve Chinese patients with AIDS, to provide evidences for standardizing HAART.Methods Seventy-four treatment-naive AIDS patients were initiated with HAART and followed up regularly for 3 years. The clinical and laboratory data, side effects and drug resistance were observed and analyzed during the follow-up period. Results Of the 74 patients, 46 were males and 28 were females, with the average age being 42 years. The mean HIV viral load was ( 2. 2 ± 2.0 ) × 105 copies/ml and the baseline mean CD4+ T lymphocyte count was (62 ± 71 )cells/μl before treatment. After treatment for 3, 6, 12, 18,24, 30 and 36 months, the percentage of undetectable HIV viral road (less than 50 copies/ml ) was 71.6%, 83.8%, 75.7%, 77.0%, 82.4%, 81.1% and 79.7% respectively, and CD4+T lymphocyte count ascended to ( 167 ± 105), ( 177 ± 129), (238 ± 137), (290 ± 158), (304 ± 191 ), (331 ± 175) and ( 352 ± 202 ) cells/μl. The increase in amplitude of CD4+ T lymphocyte count in different periods examined was different, with the period of 0-3 months post-treatment demonstrating the most obvious augmentation ( P ＜ 0. 01 ) . The most common adverse reactions were liver function injury ( 52/74,70. 3% ), hyperlipemia (52/74, 70. 3%), hematopoietic inhibition of the bone marrow (33/74, 44. 6% ),peripheral neuritis (32/74, 43.2% ) and lipoatrophy (26/74, 35. 1%). Clinical drug resistance were found in nine patients and HIV gene mutations were detected in these patients. Conclusions Chinese treatment-naive AIDS patients have achieved good virological and immunological response to generic-drugpredominant HAART regimes with low drug resistance, but relatively more side effects.