Objective:To analyze the efficacy and safety of integrase inhibitor-based single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and lamivudine/dolutegravir (3TC/DTG) in the treatment-na?ve patients with acquired immunodeficiency syndrome (AIDS).Methods:This study was a retrospective cohort study. The clinical data of treatment-na?ve AIDS patients initiating anti-retroviral therapy (ART) with B/F/TAF or 3TC/DTG and on ART for greater than or equal to 24 weeks from October 2020 to July 2023 in Shanghai Public Health Clinical Center, Fudan University were collected. The baseline human immunodeficiency virus (HIV)-1 RNA, CD4 + T lymphocyte counts at baseline and 12 weeks of treatment, and the rates of virological suppression and virological failure at 24 weeks of treatment, and levels of total cholesterol, serum creatinine, uric acid before and after treatment were compared between the B/F/TAF group and 3TC/DTG group. Independent sample t test, corrected t test, Mann-Whitney U test, Wilcoxon signed rank test, chi-square test were used for statistical analysis. Results:Among 189 treatment-na?ve AIDS patients, 141 cases were in B/F/TAF group and 48 cases in 3TC/DTG group. The HIV-1 RNA level at baseline was 1.77(0.78, 4.52)×10 5 copies/mL in the B/F/TAF group and 0.97(0.24, 2.20)×10 5 copies/mL in the 3TC/DTG group. There was a statistically significant difference between the two groups ( U=2 221.00, P=0.006).There were 77.3%(109/141) patients on B/F/TAF achieved complete virological suppression with no virological failure at week 24, and 85.4%(41/48) on 3TC/DTG achieved complete virological suppression with one (2.1%) virological failure at week 24. At 12 weeks of treatment, 92.2%(130/141) of the patients in the B/F/TAF group and 85.4%(41/48) of the patients in the 3TC/DTG group had an increase in CD4 + T lymphocyte count by more than 30% compared with baseline. The proportion of CD4 + T lymphocyte count increased by more than 100/μL from baseline in the B/F/TAF group was 67.4%(95/141), and that in the 3TC/DTG group was 52.1%(25/48). There were no significant differences between the two groups ( χ2=1.91 and 3.61, respectively, P=0.167 and 0.733).The levels of total cholesterol ( W=2 036.00, t=-5.42, respectively), serum creatinine ( W=1 098.00, 234.00, respectively), uric acid ( W=2 188.00, 299.00, respectively) and the proportion of patients with mild to moderate renal insufficiency ( χ2=22.29, 8.22, respectively) in the B/F/TAF group and 3TC/DTG group after 24 weeks of treatment were significantly higher than those before treatment (all P<0.01). Conclusions:Both B/F/TAF and 3TC/DTG are effective in terms of virological suppression and immunological recovery and have good safety profiles in treatment-na?ve patients with AIDS.

Objective:To analyze the changes of pathogen spectrum of pulmonary infection in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients before and during coronavirus disease 2019 (COVID-19) epidemic.Methods:The clinical data of hospitalized HIV infection/AIDS patients with pulmonary infection confirmed by etiology and/or imaging examinations in the Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University from January 2017 to December 2022 were collected, including the types of pathogens, the peripheral blood CD4 + T lymphocyte counts at admission due to pulmonary infection, and the treatment outcome of the patients at discharge. The changes of pathogen spectrum of pulmonary infection before COVID-19 epidemic (2017 to 2019) and during the epidemic (2020 to 2022) were analyzed, and their effects on adverse treatment outcomes (death during hospitalization or automatic discharge) were analyzed. Statistical analysis was performed using the chi-square test, trend chi-square test or Kruskal-Wallis test. Results:The proportion of patients with pulmonary infection during the epidemic was lower than that before the epidemic, the difference was statistically significant (23.01%(1 061/4 612) vs 28.68%(1 463/5 102), χ2=40.76, P<0.001). From 2017 to 2022, the proportion of hospitalized HIV infection/AIDS patients with pulmonary infection showed a downward trend ( χ2trend=8.81, P<0.001). Among the pathogens causing pulmonary infection from 2017 to 2022, bacteria, mycobacteria, and fungi were the three main pathogenic pathogens, accounting for 48.77%(1 231/2 524), 32.13%(811/2 524), and 14.34%(362/2 524), respectively. The proportion of bacterial infection decreased from 55.02%(805/1 463) before the epidemic to 40.15%(426/1 061) during the epidemic, and the proportion of fungal infection increased from 9.23%(135/1 463) to 21.39%(227/1 061), the differences were both statistically significant ( χ2=54.45 and 74.11, respectively, both P<0.001). There was no significant difference in the proportion of mycobacteria between before and during the epidemic ( P=0.169), but the proportion of Mycobacterium tuberculosis (MTB) infection decreased from 22.01%(322/1 463) before the epidemic to 15.08%(160/1 061) during the epidemic, while the proportion of nontuberculous mycobacterium (NTM) infection increased from 7.11%(104/463) to 11.78%(125/1 061), the differences were both statistically significant ( χ2=19.11 and 16.28, respectively, both P<0.001). There was a significant difference in the pathogen spectrum of pulmonary infection before and during the epidemic ( χ2=128.91, P<0.001). There was a significant difference in the peripheral blood CD4 + T lymphocyte counts of patients with MTB, NTM, Pnenmocystis, Talaromycosis marneffei and Cryptococcus infection ( H=71.92, P<0.001). There were 63.74%(109/171) of Pneumocystis infection and 67.65%(69/102) of Talaromycosis marneffei infection occurred in patients with CD4 + T lymphocyte count<50/μL. Among the patients with pulmonary infection, the proportion of patients with adverse treatment outcomes during the epidemic was higher than that before the epidemic, and the difference was statistically significant (13.29%(141/1 061) vs 10.39%(152/1 463), χ2=5.04, P=0.025). Among the patients with pulmonary infection who developed adverse treatment outcomes, the top three pathogens (from high to low) were bacteria (63.48%(186/293)), mycobacteria (27.65%(81/293)), and fungi (6.83%(20/293)). The proportion of adverse treatment outcomes caused by bacterial infection decreased during the epidemic compared with that of before the epidemic (71.71%(109/152) vs 54.61%(77/141), χ2=9.23, P=0.002), while the proportion of adverse treatment outcomes caused by fungal infection increased (2.63%(4/152) vs 11.35%(16/141), χ2=8.74, P=0.003), and the differences were both statistically significant. The proportion of adverse treatment outcomes caused by mycobacterial infection increased, but without statistically significant (23.03%(35/152) vs 32.62%(46/141), χ2=3.37, P=0.066), among which there was no difference in the proportion of adverse treatment outcomes caused by MTB infection (13.82%(21/152) vs 14.89%(21/141), χ2=0.07, P=0.793), while the proportion of adverse treatment outcomes caused by NTM infection increased (5.92%(9/152) vs 14.89%(21/141), χ2=6.41, P=0.011). There was a significant difference in the pathogen spectrum of pulmonary infection patients with adverse treatment outcomes before and during the epidemic ( χ2=12.22, P=0.007). Conclusions:Among the spectrum of pathogens causing pulmonary infection and adverse treatment outcomes of HIV infection/AIDS patients during the epidemic, compared with that before the epidemic, the proportion of bacterial decreases, while the proportion of fungi increases, and the proportion of mycobacteria remains stable with the proportion of NTM increasing. The proportion of MTB causing pulmonary infection decreases, while the proportion of MTB causing adverse treatment outcomes remains stable.

Objective:To analyze the clinical and epidemiological characteristics and changing trends of acquired immunodeficiency syndrome (AIDS)-associated talaromycosis in Shanghai City.Methods:The clinical data of patients with AIDS-associated talaromycosis hospitalized at Shanghai Public Health Clinical Center, Fudan University from Janauary 1, 2014 to December 31, 2021 were collected. The medical information included age, gender, place of origin, clinical symptoms, imaging manifestations, blood routine test, CD4 + T lymphocyte count. The chi-square test or Fisher exact probability test was used for statistical analysis. Univariate logistic regression was used to analyze the related risk factors for death. Results:From 2014 to 2021, a total of 12 165 AIDS patients were admitted, including 169 (1.4%) AIDS-assiociated talaromycosis patients. The proportions of AIDS-associated talaromycosis in AIDS inpatients from 2014 to 2021 were 1.8%(21/1 149), 1.1%(14/1 307), 1.3%(19/1 446), 0.9%(15/1 610), 1.2%(20/1 626), 1.2%(22/1 778), 1.7%(28/1 624) and 1.8%(30/1 625), respectively, which had not changed much. There was no statistically significant difference in the proportion of AIDS-associated talaromycosis in AIDS inpatients in different years ( χ2=9.50, P=0.218). Among the 169 patients, 157 cases (92.9%) were male, with the age of (37.9±12.2) years, and 35 were from Jiangxi Province, 31 from Shanghai Municipality, 29 from Zhejiang Province, 17 from Anhui Province, 14 from Fujian Province, 11 from Jiangsu Province, eight from Hunan Province, four from Heilongjiang Province, three cases each from Guangxi Zhuang Autonomous Region, Guizhou Province and Henan Province, two cases each from Hubei Province, Shandong Province, Shanxi Province, Yunnan Province and Guangdong Province, and one case from Chongqing Municipality. Patients from non-traditional endemic areas did not find a clear history of living in traditional endemic areas. Of 169 patients, 143(84.6%) cases had fever, 73(43.2%) had respiratory symptoms, and 26(15.4%) had rash during the course of the disease, 147(87.0%) had pulmonary imaging abnormalities, 94(55.6%) were complicated by other pathogens, and 44(26.0%) had hepatosplenomegaly, 137(81.1%) had CD4 + T lymphocyte count <50/μL. Twenty-three patients died, with the total fatality rate of 13.6%. The overall mortality rate showed a downward trend year by year. There was a statistically significant difference in the case fatality rate of AIDS-associated talaromycosis in different years (Fisher exact probability test, P=0.046). The result of univariate logistic regression model showed that patients with platelet count<50×10 9/L had an increased risk of death (odds ratio ( OR)=3.33, 95% confidence interval ( CI) 1.13 to 9.81, P=0.029). Conclusions:The overall change of AIDS-associated talaromycosis inpatients in Shanghai is not significant, while the prevalence rate has increased slightly in recent two years. The case fatality rate is declining year by year. The proportions of patients without a history of living in or traveling to epidemic areas and without rash as the first manifestation are high, and the main clinical manifestation is multi-system damage. Patients with platelet count<50×10 9/L have an increased risk of death.

Objective:To investigate the diagnostic performance of Xpert Mycobacterium tuberculosis/rifampin (Xpert MTB/RIF) assay for pulmonary tuberculosis (TB) in patients with acquired immunodeficiency syndrome (AIDS). Methods:Clinical data of 226 patients with AIDS and suspected pulmonary TB in Shanghai Public Health Clinical Center, Fudan University from July 2017 to November 2019 were retrospectively analyzed. Fluorescence staining microscopy of sputum smear, BACTEC MGIT 960 liquid culture (or Roche solid culture) and Xpert MTB/RIF assay were implemented respectively. The sensitivity and specificity of Xpert MTB/RIF in the diagnosis of Mycobacterium tuberculosis (MTB) infection and rifampin resistance were analyzed. Results:Totally 226 patients of suspected pulmonary TB were enrolled. There were 94(41.6%) patients had positive mycobacterium culture, in which 51 (54.3%) were MTB and 43 (45.7%) were nontuberculous mycobacteria (NTM). Using the positive MTB culture of sputum and mycobacterial protein from BCG of Rm 0.64 in electrophoresis (MPB64) as reference standard, the sensitivity and specificity of Xpert MTB/RIF assay for MTB diagnosis were 72.6%(95% confidence interval ( CI) 66.7%-78.4%) and 97.1% (95% CI 95.0%-99.3%), respectively. The sensitivity and specificity of Xpert MTB/RIF assay for MTB diagnosis in patients with positive sputum smear were 76.7%(95% CI 67.7%-85.8%) and 90.0(95% CI 83.6%-96.5%), respectively. The sensitivity and specificity of Xpert MTB/RIF assay for MTB diagnosis in patients with negative sputum smear were 50.0%(95% CI 41.8%-58.2%)and 99.3%(95% CI 97.9%-100.0%), respectively. With phenotypic resistance as reference standard, the sensitivity and specificity of Xpert MTB/RIF assay for rifampicin resistance were 75.0% and 100.0%, respectively. Conclusion:Among AIDS patients, the performance of Xpert MTB/RIF assay for pulmonary TB diagnosis is pretty good and could differentiate MTB from NTM rapidly, which has good application value.

Since the founding of the People′s Republic of China in 1949, China′s vaccination work has been making remarkable achievements. However, under the state of emergency, such as major infectious disease outbreaks, major natural disasters, vaccine-related events, large-scale population entry at the border, vaccination services confront many challenges, and the emergency plan for vaccination services in most areas is still in the exploratory stage. Based on the experience at home and abroad, combined with China′s relevant policies, technical guidelines and evidence, this study provides suggestions for vaccination services in aforementioned emergency events, in order to standardize the development and implementation of vaccination services under the state of emergency in China.

Since the founding of the People′s Republic of China in 1949, China′s vaccination work has been making remarkable achievements. However, under the state of emergency, such as major infectious disease outbreaks, major natural disasters, vaccine-related events, large-scale population entry at the border, vaccination services confront many challenges, and the emergency plan for vaccination services in most areas is still in the exploratory stage. Based on the experience at home and abroad, combined with China′s relevant policies, technical guidelines and evidence, this study provides suggestions for vaccination services in aforementioned emergency events, in order to standardize the development and implementation of vaccination services under the state of emergency in China.

Objective:To analyze the pathological patterns, clinical features, and prognosis in patients with human immunodeficiency virus (HIV) infection complicated with kidney disease.Methods:A retrospective analysis of 21 renal damage cases in HIV-infected patients undergoing renal biopsy from June 2016 to November 2019 in Shanghai Public Health Clinical Center, Fudan University was conducted. The clinical features, renal pathological patterns, therapies and outcomes were summarized and analyzed.Results:The age of 21 patients was (45.4±11.0) years. There were 19 men and two women. The CD4 + T lymphocyte count was (473.7±218.4) cells/μL. The HIV RNA levels were measured in 20 patients, and 13 cases (65.0%) were less than 40 copies/mL. A total of 18 cases (85.7%) had initiated antiretroviral therapy before renal biopsy, and the treatment time was 12 (1, 47) months. As for the clinical diagnosis, 14 cases (66.7%) were nephrotic syndrome and seven cases (33.3%) were nephritic syndrome. Renal pathology reports showed that HIV immune-complex kidney disease was the most common pathology pattern, accounting for 42.9% (9/21), followed by podocytopathy and diabetic nephropathy, both accounting for 23.8% (5/21), respectively. The IgA nephropathy (23.8%, 5/21) was the most common subtype of HIV immune-complex kidney disease, while minimal change disease (19.0%, 4/21) was the most common one of podocytopathy. However, classic HIV-associated nephropathy was not found in the study. The follow-up period was (12.5±9.2) months. During this period, the nephropathy conditions of nine patients were improved, eight were stable, two deteriorated, and two died. Conclusions:IgA nephropathy, minimal change disease and diabetic nephropathy are the top three patterns of renal pathology in patients with HIV infection. Most cases have good prognosis after treatments. For HIV-infected patients with serious renal damage, timely kidney biopsy is vital to determine pathological pattern, and to subsequently guide the clinical treatment and evaluate the prognosis.

Objective:To investigate the risk factors of cardiovascular diseases (CVD) in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients who did not receive anti-retroviral therapy (ART), and to provide reference for the follow-up ART scheme selection and CVD monitoring and management.Methods:A cross-sectional survey was conducted on 372 HIV/AIDS patients who did not initiate ART in the Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University from November 2018 to January 2020. According to the structured questionnaire, the basic information of HIV/AIDS patients, traditional risk factors of CVD (including smoking status, hypertension, diabetes, CVD family history) and HIV related factors were collected. The Framingham risk score and the data collection on adverse events of anti-HIV drugs (D∶A∶D (R)) score were used to evaluate the risk of CVD for 10 years. Logistic regression was used to analyze the influencing factors of CVD risk score≥10% in 10 years.Results:Among the 372 patients, 339(91.13%) were male and 33 (8.87%) were female. The age was 34(18, 80) years. The incidence of hypertension and diabetes were 12.20%(41/336) and 5.71%(21/368), respectively. There were 111 cases (30.16%, 111/368) with CD4 + T lymphocyte count <200/μL. Among 368 patients who underwent blood lipid test, high density lipoprotein-cholesterol (HDL-C) decreased in 199 cases (54.08%), triglyceride increased in 136 cases (36.96%), total cholesterol elevated in 44 cases (11.96%), and low density lipoprotein-cholesterol increased in 36 cases (9.78%). Statins were administrated in four cases (9.09%, 4/44). Among the 365 patients who met the D∶A∶D (R) score, age≥50 years old (odds ratio ( OR)=216.71, 95% confidence interval ( CI) 72.70-749.01, P<0.01) and HDL-C <1.0 mmol/L ( OR=6.35, 95% CI 2.22-18.09, P<0.01) were risk factors for 10-year CVD risk score≥10%. Among 233 patients who met the requirements of Framingham score, age≥50 years old ( OR=7.79, 95% CI 3.24-18.75, P<0.01) and CD4 + T lymphocyte count <200/μL( OR=1.88, 95% CI 0.10-3.56, P<0.05) were risk factors for 10-year CVD risk≥10%. Conclusions:There are many CVD risk factors among patients who have not initiated ART. The patients have high scores of 10-year CVD risk, while the intervention rate is low. Patients have higher CVD risks when age≥50 years old, CD4 + T lymphocyte count <200/μL and HDL-C <1.0 mmol/L. Therefore, screening and risk assessment of CVD risk factors should be included in the routine management and care of HIV/AIDS patients without ART initiation.

Purpose: Cancer stem cells (CSCs) are naturally resistant to chemotherapy, explaining why tumorrelapse frequently occurs after initial regression upon administration of chemotherapeuticagents in most cases. A CSC population characterized by CD13 expression has been identifiedin hepatocellular carcinoma (HCC). In the current study, we aimed to clarify the molecularmechanism by which it escapes conventional therapies. Materials and Methods: Here, we used flow cytometry to examine the percentage of CD13+ CSCs in HepG2 andHuH7 cells after chemotherapy. Using in vitro isotope labeling technique, we comparedmetabolic pathways between CD13+ and CD13– subpopulations. Using co-immunoprecipitationand western blotting, we determined the target expressions in protein levels underdifferent conditions. We also performed immunohistochemistry to detect the target proteinsunder different conditions. Animal models were constructed to verify the potential role oftyrosine metabolism in post-chemotherapeutic relapse in vivo. Results: We observed that quiescent CD13+ CSCs are enriched after chemotherapy in HCCs, andserve as a reservoir for recurrence. Mechanistically, CD13+ CSCs were dependent on aerobicmetabolism of tyrosine rather than glucose as energy source. Tyrosine metabolism alsogenerated nuclear acetyl-CoA to acetylate and stabilize Foxd3, thereby allowing CD13+ CSCscells to sustain quiescence and resistance to chemotherapeutic agents. Conclusion These findings encourage further exploration of eliminating CD13+ cells by targeting specificmetabolic pathways to prevent recurrence in HCCs.

Objective To explore the hemodynamic assessment after radical surgery in children with tetralogy of Fallot (TOF) by both echocardiography and Mostcare monitor. Methods Clinical data of 63 children with TOF who underwent radical surgery in our hospital from February 2016 to June 2018 were retrospectively analyzed, including 34 males and 29 females, aged 6-24 (9.82±5.77) months. There were 19 patients undergoing transannular patch reconstruction of the right ventricular outflow tract (a transannular patch group) while 44 patients retained the pulmonary valve annulus (a non-transannular patch group) . The echocardiography and Mostcare monitor parameters were recorded and brain natriuretic peptide was tested at the time points of 0, 8, 12, 24 and 48 hours after operation (T 0, T 1, T 2, T 4) to analyze their correlations and the change trend at different time points after radical surgery. Results The left ventricular ejection fraction at T 1 (43.49%±3.82%) was lower than that at T 0 (48.29%±4.55%), T 2 (45.83%±3.69%), T 3 (53.76%±4.43%) and T 4 (60.54%±3.23%, P<0.05). The cardiac index at T 1 (1.85±0.35 L·min−1·m−2) was lower than that at T 0 (2.11±0.38 L·min−1·m−2), T 2 (2.07±0.36 L·min−1·m−2), T 3 (2.42±0.37 L·min−1·m−2) and T 4 (2.82±0.42 L·min−1·m−2, P<0.05). The cardiac circulation efficiency at T1 (0.19±0.05) was lower than that at T 0 (0.22±0.06), T 2 (0.22±0.05), T 3 (0.28±0.06) and T 4 (0.34±0.06, P<0.05). The right ventricular two-chambers view fraction area change at T 1 (23.17%±3.11%) was lower than that at T 0 (25.81%±3.74%), T 2 (25.38%±3.43%), T 3 (30.60%±4.50%) and T 4 (36.94%±5.85%, P<0.05). The pulse pressure variability was the highest at T 0 (18.76%±3.58%), followed by T 1 (14.81%±3.32%), T 2 (12.44%±2.94%), T 3 (10.39%±2.96%) and T 4 (9.18%±1.92%, P<0.05). The blood brain natriuretic peptide was higher at T 1 (846.67±362.95 pg/ml) than that at T 0 (42.60±18.06 pg/ml), T 2 (730.95±351.09 pg/ml), T 3 (510.98±290.39 pg/ml) and T 4 (364.41±243.56 pg/ml, P<0.05). There was no significant difference in left ventricular ejection fraction, cardiac circulation efficiency and heart index between the two groups (P>0.05). The right ventricular two-chambers view fraction area change of the transannular patch group was significantly lower than that of the nontransannular patch group at each time point (P<0.05). The blood brain natriuretic peptide and pulse pressure variability of the transannular patch group were significantly higher than those of the non-transannular patch group (P<0.05). Left ventricular ejection fraction was positively correlated with cardiac index (r=0.637, P=0.001) and cardiac circulation efficiency (r=0.462, P=0.001) while was significantly negatively correlated with blood brain natriuretic peptide (r=–0.419, P=0.001). Conclusion Both methods can accurately reflect the state of cardiac function. Mostcare monitor has a good consistency with echocardiography. Using transannular patch to recontribute right ventricular outflow tract in operation has more influence on right ventricular systolic function. The Mostcare monitor can guide the hemodynamic management after surgery in real time, continuously and accurately.