1.Advances in multidimensional detection strategies and in vitro/in vivo modeling of the HIV latent reservoir
Jiahao JI ; Fuchun WANG ; Luying ZHU ; Tong ZHANG
Chinese Journal of Experimental and Clinical Virology 2025;39(5):645-651
Latent human immunodeficiency virus(HIV)infection remains the principal barrier to functional cure. Proviruses integrate into multiple immune cell types and persist long term,creating a heterogeneous reservoir. Accurate identification of latent infection and assessment of proviral intactness and function are prerequisites for progress toward cure. Here we compare key reservoir assays and their trade-offs,including HIV DNA quantification by quantitative PCR(qPCR)and droplet digital PCR(ddPCR),detection of replication-competent virus by the quantitative viral outgrowth assay(QVOA),and inducible transcription/protein readouts such as Tat/Rev induced limiting dilution assay(TILDA)and viral protein spot assay(VIP-SPOT). We also outline applications of spatial transcriptomics and in situ hybridization(RNAscope/DNAscope)for anatomic localization and functional analysis. We also summarize advances in experimental models,spanning in-vitro systems(primary T-cell and myeloid latency models)and in-vivo platforms(humanized mice and rhesus macaque SHIV models)used for mechanism studies and intervention testing. Looking ahead,coordinated use of these orthogonal tools can improve estimates of reservoir size,inducibility,and tissue distribution,and provide a practical platform for translational studies toward functional cure.
2.Impact of comorbidities on in-hospital mortality of community-acquired pneumonia in elderly patients
Yanting HAO ; Fan ZHANG ; Hua ZHANG ; Fuchun ZHANG
Chinese Journal of Geriatrics 2025;44(3):311-316
Objective:To analyze the association between the number and type of comorbidities—specifically high-risk(HR)and at-risk(AR)—and the risk of in-hospital mortality among elderly patients aged 65 years and older with community-acquired pneumonia(CAP).Methods:A retrospective study was conducted to gather basic information, along with diagnostic and treatment data, for elderly CAP patients hospitalized at the Third Hospital of Peking University from January 1, 2010, to December 31, 2019.Binary logistic regression was employed to examine the relationships between both the number and type of coexisting chronic diseases and in-hospital mortality in this patient population.Results:This study included a total of 2 466 elderly patients aged ≥65 years with CAP, of whom 428(17.36%)died during hospitalization.The presence of HR comorbidities was associated with an increased likelihood of in-hospital mortality ( OR=1.81, 95% CI: 1.44-2.28, P<0.001).Similarly, the presence of AR comorbidities was significantly linked to higher in-hospital mortality ( OR=15.72, 95% CI: 7.39-33.42, P<0.001).The risk of mortality escalated with the accumulation of AR comorbidities, with risk ratios ranging from 5.46 to 44.72.Notably, elderly CAP patients with 4 to 5 AR comorbidities in conjunction with HR comorbidities exhibited the highest mortality risk ( OR=85.56, 95% CI: 19.86-368.67, P<0.001).Among the comorbidities assessed, chronic liver disease emerged as the most significant factor associated with mortality in elderly CAP patients, with an importance coefficient of 0.258. Conclusions:In addition to specific comorbidities, the total number of combined comorbidities and the interplay between AR and HR comorbidities may significantly influence the outcomes of hospitalized CAP patients aged 65 years and older.Therefore, it is essential to carefully consider the diagnosis and management of comorbidities in elderly CAP patients to mitigate their risk of mortality.
3.Advances in multidimensional detection strategies and in vitro/in vivo modeling of the HIV latent reservoir
Jiahao JI ; Fuchun WANG ; Luying ZHU ; Tong ZHANG
Chinese Journal of Experimental and Clinical Virology 2025;39(5):645-651
Latent human immunodeficiency virus(HIV)infection remains the principal barrier to functional cure. Proviruses integrate into multiple immune cell types and persist long term,creating a heterogeneous reservoir. Accurate identification of latent infection and assessment of proviral intactness and function are prerequisites for progress toward cure. Here we compare key reservoir assays and their trade-offs,including HIV DNA quantification by quantitative PCR(qPCR)and droplet digital PCR(ddPCR),detection of replication-competent virus by the quantitative viral outgrowth assay(QVOA),and inducible transcription/protein readouts such as Tat/Rev induced limiting dilution assay(TILDA)and viral protein spot assay(VIP-SPOT). We also outline applications of spatial transcriptomics and in situ hybridization(RNAscope/DNAscope)for anatomic localization and functional analysis. We also summarize advances in experimental models,spanning in-vitro systems(primary T-cell and myeloid latency models)and in-vivo platforms(humanized mice and rhesus macaque SHIV models)used for mechanism studies and intervention testing. Looking ahead,coordinated use of these orthogonal tools can improve estimates of reservoir size,inducibility,and tissue distribution,and provide a practical platform for translational studies toward functional cure.
4.Impact of comorbidities on in-hospital mortality of community-acquired pneumonia in elderly patients
Yanting HAO ; Fan ZHANG ; Hua ZHANG ; Fuchun ZHANG
Chinese Journal of Geriatrics 2025;44(3):311-316
Objective:To analyze the association between the number and type of comorbidities—specifically high-risk(HR)and at-risk(AR)—and the risk of in-hospital mortality among elderly patients aged 65 years and older with community-acquired pneumonia(CAP).Methods:A retrospective study was conducted to gather basic information, along with diagnostic and treatment data, for elderly CAP patients hospitalized at the Third Hospital of Peking University from January 1, 2010, to December 31, 2019.Binary logistic regression was employed to examine the relationships between both the number and type of coexisting chronic diseases and in-hospital mortality in this patient population.Results:This study included a total of 2 466 elderly patients aged ≥65 years with CAP, of whom 428(17.36%)died during hospitalization.The presence of HR comorbidities was associated with an increased likelihood of in-hospital mortality ( OR=1.81, 95% CI: 1.44-2.28, P<0.001).Similarly, the presence of AR comorbidities was significantly linked to higher in-hospital mortality ( OR=15.72, 95% CI: 7.39-33.42, P<0.001).The risk of mortality escalated with the accumulation of AR comorbidities, with risk ratios ranging from 5.46 to 44.72.Notably, elderly CAP patients with 4 to 5 AR comorbidities in conjunction with HR comorbidities exhibited the highest mortality risk ( OR=85.56, 95% CI: 19.86-368.67, P<0.001).Among the comorbidities assessed, chronic liver disease emerged as the most significant factor associated with mortality in elderly CAP patients, with an importance coefficient of 0.258. Conclusions:In addition to specific comorbidities, the total number of combined comorbidities and the interplay between AR and HR comorbidities may significantly influence the outcomes of hospitalized CAP patients aged 65 years and older.Therefore, it is essential to carefully consider the diagnosis and management of comorbidities in elderly CAP patients to mitigate their risk of mortality.
5.Antibiotic-loaded bone cement enhances ability of tibial cortex transverse transport for treating infected wounds
Junpeng LIU ; Xingchen YAO ; Hui ZHAO ; Ziyu XU ; Yue WU ; Fuchun PEI ; Lin ZHANG ; Xinru DU
Chinese Journal of Tissue Engineering Research 2024;28(29):4599-4604
BACKGROUND:Diabetic foot patients with wound infections constitute a large patient population,and there is currently no satisfactory treatment approach. OBJECTIVE:To investigate the clinical efficacy of a modified tibial cortex transverse transport combined with antibiotic-loaded bone cement for treating refractory diabetic foot ulcers. METHODS:A total of 46 diabetic foot ulcers patients,27 males and 19 females,with an average age of 64.37 years,were selected from Beijing Chaoyang Hospital,Capital Medical University and Beijing Chaoyang Integrative Medicine Rescue and First Aid Hospital from January 2020 to January 2023.All of them underwent the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement treatment.Ankle-brachial index,WIFi(Wound/Ischemia/Foot infection)classification,pain visual analog scale score,and ulcer area were recorded before and 3 months after surgery. RESULTS AND CONCLUSION:(1)The mean ulcer healing time for the 46 patients was(58.07±24.82)days.At 3 months postoperatively,there were significant improvements in ankle-brachial index,pain visual analog scale score,ulcer area,and WIFi classification in 46 patients,as compared to the preoperative values,with statistically significant differences(P<0.05).Two patients experienced pin-tract infections,without infection or ulcer recurrence during the follow-up period.(2)These findings indicate that the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement effectively alleviates patients'pain,improves lower limb circulation,controls infections,and promotes ulcer healing.
6.Construction and validation of a nomogram for predicting in-hospital postoperative heart failure in elderly patients with hip fracture
Yuanmei LIU ; Yicheng FU ; Jingxin HAO ; Fuchun ZHANG ; Huilin LIU
Journal of Peking University(Health Sciences) 2024;56(5):874-883
Objective:To construct and validate a nomogram for prediction of in-hospital postoperative heart failure(PHF)in elderly patients with hip fracture.Methods:This was a retrospective cohort study.The patients aged ≥65 years undergoing hip fracture surgery in Peking University Third Hospital from July 2015 to December 2023 were enrolled.The patients admitted from July 2015 to December 2021 were divided into a development cohort,and the others admitted from January 2022 to December 2023 in to a validation cohort.The patients'clinical data were collected from the electronic medical record sys-tem.Univariate and multivariate Logistic regression were employed to screen the predictors for PHF in the patients.The R software was used to construct a nomogram.Internal and external validation were per-formed by the Bootstrap method.The discriminatory ability of the model was determined by the area un-der the receiver operating characteristic curve(AUC).The calibration was evaluated by the calibration plot and Hosmer-Lemeshow goodness-of-fit test.Decision curve analysis(DCA)was performed to assess the clinical utility.Results:In the study,944 patients were eventually enrolled in the development co-hort,and 469 were in the validation cohort.A total of 54(5.7%)patients developed PHF in the deve-lopment cohort,and 18(3.8%)patients had PHF in the validation cohort.Compared with those from non-PHF group,the patients from PHF group were older,had higher prevalence of heart disease,hyper-tension and pulmonary disease,had poorer American Society of Anesthesiologists(ASA)classification(Ⅲ-Ⅳ),presented with lower preoperative hemoglobin level,lower left ventricular ejection fraction,higher preoperative serum creatinine,received hip arthroplasty and general anesthesia more frequently.Multivariate Logistic regression analysis showed that age(OR=1.071,95%CI:1.019-1.127,P=0.008),history of heart disease(OR=5.360,95%CI:2.808-10.234,P<0.001),preoperative he-moglobin level(OR=0.979,95%CI:0.960-0.999,P=0.041),preoperative serum creatinine(OR=1.007,95%CI:1.001-1.013,P=0.015),hip arthroplasty(OR=2.513,95%CI:1.259-5.019,P=0.009),and general anesthesia(OR=2.024,95%CI:1.053-3.890,P=0.034)were the independent predictors for PHF in elderly patients with hip fracture.Four preoperative predictors were incorporated to construct a preoperative nomogram for PHF in the patients.The AUC values of the nomo-gram in internal and external validation were 0.818(95%CI:0.768-0.868)and 0.873(95%CI:0.805-0.929),indicating its good accuracy.The calibration plots and Hosmer-Lemeshow goodness-of-fit test(internal validation:x2=9.958,P=0.354;external validation:x2=5.477,P=0.791)showed its satisfactory calibration.Clinical usefulness of the nomogram was confirmed by decision curve analysis.Conclusion:An easy-to-use nomogram for prediction of in-hospital PHF in elderly patients with hip fracture is well developed.This preoperative risk assessment tool can effectively identify patients at high risk of PHF and may be useful for perioperative management optimization.
7.Comparison of clinical manifestations, laboratory characteristics and treatment of 153 patients with acute and chronic brucellosis
Huiqin YANG ; Haipeng ZHENG ; Xudan CHEN ; Ying TAN ; Fuchun ZHANG ; Linghua LI ; Jian WANG
Chinese Journal of Endemiology 2024;43(5):398-403
Objective:To learn about the clinical manifestations, laboratory characteristics and treatment of patients with acute and chronic brucellosis.Methods:Clinical data of 153 brucellosis patients admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from 2012 to 2022 were retrospectively collected, including general information, epidemiological characteristics, clinical manifestations, laboratory test results, imaging examination results, treatment and prognosis. According to the course of disease < 180 d and ≥180 d, these patients were divided into acute brucellosis group and chronic brucellosis group, and the clinical data of the two groups of patients were compared and analyzed.Results:A total of 153 patients with brucellosis were included, including 119 in the acute brucellosis group and 34 in the chronic brucellosis group. The age was (46.2 ± 13.8) years old, with 115 males (75.2%) and 38 females (24.8%), and 85 patients (55.6%) were occupational exposed. Complications occurred in 90 patients (58.8%), and the incidence of complications in the acute brucellosis group was lower than that in the chronic brucellosis group [76.5% (26/34) vs 53.8% (64/119), χ 2 = 5.62, P = 0.018]. The most common clinical manifestations were fever and arthralgia, with 128 cases (83.7%) and 124 cases (81.0%), respectively. The incidence of fever in the acute brucellosis group was higher than that in the chronic brucellosis group [87.4% (104/119) vs 70.6% (24/34), χ 2 = 5.46, P = 0.019], while the incidence of arthralgia was lower than that in the chronic brucellosis group [77.3% (92/119) vs 94.1% (32/34), χ 2 = 4.83, P = 0.027]. In laboratory tests, the positive rate of blood culture was 59.5% (91/153), and it was higher in the acute brucellosis group than that in the chronic brucellosis group [67.2% (80/119) vs 32.4% (11/34), P < 0.05]. The incidence of elevated procalcitonin [PCT, 58.6% (58/99) vs 24.1% (7/29), χ 2 = 10.65, P = 0.001] and the incidence of liver dysfunction [33.9% (40/118) vs 15.2% (5/33), χ 2 = 4.33, P = 0.037] in the acute brucellosis group were higher than those in the chronic brucellosis group. In the imaging examination, 61 patients (39.9%) experienced bone destruction, and the incidence of bone destruction in the chronic brucellosis group was higher than that in the acute brucellosis group [55.9% (19/34) vs 35.3% (42/119), χ 2 = 4.68, P = 0.031]. All patients were treated with antibiotics, with a median of 3 and 4 types of antibiotics used in the acute and chronic brucellosis groups, respectively. The overall incidence of adverse drug reactions was 5.2% (8/153). After treatment, 65 cases (42.5%) recovered, 70 cases (45.8%) improved, and 18 cases (11.8%) did not recover. Conclusions:The main clinical manifestations of brucellosis patients are fever and arthralgia, with a high incidence of complications. All patients are treated with combined antibiotics therapy. Patients in acute brucellosis group have a higher incidence of fever, positive blood culture, elevated PCT and abnormal liver function, while patients in chronic brucellosis group have a higher incidence of complications, arthralgia and bone destruction.
8.Micro-osteotomy bone transport combined with vacuum sealing drainage for the treatment of diabetic foot:A retrospective cohort study of 128 patients from two centers
Junpeng LIU ; Xinru DU ; Xingchen YAO ; Ziyu XU ; Fuchun PEI ; Lin ZHANG ; Hui ZHAO
The Journal of Practical Medicine 2024;40(18):2590-2596
Objective To assess the effectiveness of enhanced tibial transverse transport(TTT)in con-junction with vacuum-assisted closure(VAC)therapy for managing recalcitrant diabetic foot ulcers.Methods A retrospective analysis was conducted on data from diabetic foot patients with Wagner grade≥2 who were treated at Beijing Chaoyang Hospital and Beijing Chaoyang Hospital of Integrated Traditional Chinese and Western Medicine between July 2020 and December 2022.The patients were categorized into three groups based on their treatment regimen:VSD treatment(VSD group),modified TTT treatment(TTT group),and combined application of TTT and VSD(combined group).A one-year follow-up was performed to assess general data,ulcer area before and three months after surgery,ankle brachial index,visual analog pain score,as well as adverse events within one year post-surgery among the three groups.Results The VSD group consisted of 43 patients,while the TTT group consisted of 43 patients,and the combined group consisted of 42 patients.There were no statistically significant differences in baseline characteristics among the three groups(P>0.05).Patients in the VSD group had longer ulcer healing time,higher pain scores,lower ankle brachial index(P<0.05),larger ulcer area(P=0.029),and higher one-year ulcer recurrence rate compared to those in the TTT group.On the other hand,patients in the combined group had shorter ulcer healing time compared to those in the TTT group(P=0.046).However,there were no significant differences observed between these two groups regarding ulcer area(P=0.362),pain scores(P=0.932),ankle brachial index(P=0.671),and one-year ulcer recurrence rate(P=0.710).Conclusions The efficacy of modified TTT surpasses that of VSD in promoting ulcer healing,alleviating pain,and enhancing lower limb circulation.Furthermore,the combination of VSD with modified TTT demonstrates a potential to further expedite wound healing time.
9.Efficacy and safety of the 12-week sofosbuvir-coblopasvir regimen in treatment of chronic hepatitis C
Wei ZHANG ; Song ZHAI ; Hong DU ; Fuchun JING ; Limei WANG ; Ye ZHANG ; Bibo KANG ; Jiuping WANG ; Shuangsuo DANG ; Jianqi LIAN ; Hong JIANG
Journal of Clinical Hepatology 2023;39(3):539-545
Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of treatment, and the secondary endpoint was the effect of the 12-week treatment on liver biochemical parameters. The non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between groups. Results A total of 101 patients were included in the analysis, among whom there were 55 male patients (54.5%) and 46 female patients, and the median age was 53 years. Among these patients, 12.8% had liver cirrhosis, 1.0% had liver cancer, 3.0% were treatment-experienced patients, and 3.0% had type 2 diabetes. As for genotype distribution, 8% had CHC genotype 1, 60% had CHC genotype 2, 19% had CHC genotype 3, and 6% had CHC genotype 6, and genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 rate of 100%, with a significant reduction in the serum level of alanine aminotransferase (ALT) from baseline to week 12 of treatment ( P < 0.05). Among these patients, 22.7% had concomitant medications such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.
10.Clinical and laboratory characteristics of mpox patients in Guangzhou City
Huiqin YANG ; Haipeng ZHENG ; Xudan CHEN ; Ying TAN ; Fuchun ZHANG ; Jian WANG ; Linghua LI
Chinese Journal of Infectious Diseases 2023;41(11):695-700
Objective:To analyze the clinical and laboratory characteristics of mpox patients in Guangzhou City.Methods:The general conditions, symptoms and signs, and laboratory test results of mpox patients admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from June 8 to June 21, 2023 were collected. The clinical characteristics of human immunodeficiency virus (HIV)-infected patients and HIV-negative patients were compared.Independent sample t test, Mann-Whitney U test and Fisher exact probability method were used for statistical analysis. Results:Nineteen mpox patients were included in this study, none of them had been vaccinated with smallpox vaccine. All of them were identifed as gay men with an age of (33.2±6.4) years. And all of them had sex with men within 21 days of onset. There were eight cases with HIV infection and syphilis, respectively. All of these 19 patients had skin lesions which were the first symptom of 15 patients, and appeared during the course of the disease of four patients. Other common symptoms and signs were lymph node enlargement (17 cases), lymph node tenderness (15 cases), pharyngeal congestion (15 cases), tonsil enlargement (13 cases), fever (11 cases) and pruritus (10 cases). There were 13 cases with elevated CD8 + T lymphocytes, interleukin-10 level and procalcitonin level, respectively, 12 cases with elevated serum amyloid A level, and seven cases with elevated blood lymphocyte count. Eight patients were infected with HIV, including one acute infection and seven chronic infections (all of them had received regular antiviral therapy and had a CD4 + T lymphocyte count of 657(400, 757)/μL before onset). There were no significant differences in age ( t=1.55), incidence of complications (Fisher exact probability method), number of skin lesions ( Z=-0.21), incidence of lymph node enlargement (Fisher exact probability method), incidence of fever (Fisher exact probability method), duration of fever ( Z=-0.48), lymphocyte count ( t=-1.55), CD4 + T lymphocyte count ( Z=-0.17) and CD8 + T lymphocyte count ( Z=-1.49) between the HIV-infected patients and HIV-negative patients (all P>0.05). The number of skin lesions was 19(6, 26), and the locations of skin lesions were mainly in perineum and nearby areas (17 cases). The most frequent morphology of skin lesions at admission were papules (15 cases), eschar (15 cases) and pustules (12 cases). All patients recovered after topical medication and symptomatic treatment. Conclusions:Mpox mainly occurs in young and middle-aged men who have sex with men in Guangzhou City. Skin lesions, lymph node enlargement accompanied by tenderness, pharyngeal congestion, tonsil enlargement and fever are the most common features. Common laboratory abnormities are elevated inflammatory markers. The clinical characteristics of HIV-infected patients with normal immune function are similar to those of HIV-negative patients.

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