Atherosclerosis is the pathological basis of a variety of cardiovascular diseases,which are still the leading cause of human death worldwide.Ferroptosis is a kind of iron dependent non-apoptotic cell death mode,which is closely related to various physiological mechanisms.Recent studies have found that ferroptosis in macrophages plays an important role in the occurrence and development of atherosclerosis.Based on the imbalance of iron metabolism in macrophages,this paper reviews the correlation between ferroptosis in macrophages and atherosclerosis in terms of the interaction between ferroptosis in macrophages and lipid peroxidation,inflammation,oxidative stress,etc.,in order to provide new ideas for the study of the pathogenesis of atherosclerosis.

Objective　To understand the impact of early and timely treatment and initial antiviral treatment regimen on mortality and attrition of antiretroviral therapy. Methods A retrospective cohort study was conducted using download data on antiretroviral therapy for HIV-infected patients in Liuzhou City, Guangxi Province, from the database of the Basic Information System for AIDS Control and Prevention (BISAC) from 2010 to 2020. The Cox proportional risk regression model was used to analyze the influencing factors of mortality and attrition. Results A total of 15 713 infected patients were included, including 53.4% aged 18-<50 years, 69.4% male, 61.0% farmer, 75.1% CD4 count <350 cells /μL before initial antiviral treatment, the overall mortality rate was 4.30/100 person-years, and the overall attrition was 2.42/100 person-years. The results of Cox regression analysis showed that the influencing factors of mortality were pretreatment CD4 counts of 350-<500 cells/μL(AHR=0.72, 95%CI: 0.63-0.81) and ≥500 cells/μL (AHR= 0.64, 95%CI: 0.55-0.76); duration from diagnosis to initial antiviral treatment 91-180 days (AHR=1.25, 95%CI: 1.08-1.45), 181-365 days (AHR=1.26, 95%CI: 1.08-1.47), and ≥365 days (AHR=1.26, 95%CI: 1.11-1.44); initial antiviral treatment regimens of D4T+3TC+EFV/NVP (AHR=1.47, 95%CI: 1.32-1.63) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.73, 95%CI: 1.50-1.99). Factors affecting attrition were pretreatment CD4 counts of 350-499 cells/μL (AHR=1.32, 95%CI: 1.16-1.50) and ≥500 cells/μL (AHR=1.28, 95%CI: 1.10-1.50); interval from HIV positivity confirmation to initial dosing ≥365 days (AHR=1.21, 95%CI: 1.04-1.40), initial antiviral treatment regimens of TDF+3TC+NVP (AHR=1.32, 95%CI: 1.13-1.55), AZT+3TC+EFV/NVP (AHR=1.43, 95%CI: 1.26-1.62) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.33, 95CI%: 1.06-1.67). Conclusions　Early and timely treatment and the initial antiviral treatment regimen of TDF+3TC+EFV have good efficacy, but attention should be paid to the high risk of attrition of HIV-infected people with high CD4 count before treatment.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective To evaluate the effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, so as to provide insights into echinococcosis control. Methods Administrative villages were sampled using a multi-stage cluster random sampling method from Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, and all residents at ages of 12 years and older in the sampled villages were screened for echinococcosis, and schools were sampled using a cluster sampling method, and all children at ages of 12 years and older in the sampled schools were screened for echinococcosis. Domestic dogs were sampled using a systematic random sampling method, and one domestic dog stool sample was collected from each household. Stray dog stool samples were collected outside the villages, and Echinococcus coproantigens were detected using enzyme-linked immunosorbent assay in domestic and stray dogs. In addition, echinococcosis was screened in sheep and cattle in designated slaughterhouses in Tianzhu Tibetan Autonomous County. The trends in the prevalence of echinococcosis in humans and livestock and the positive rate of Echinococcus coproantigens in dogs were examined with the Cochran-Armitage trend test. In addition, individuals screened for echinococcosis were randomly sampled from 2007 to 2022 for survey on the awareness of echinococcosis control knowledge. Results A total of 290 356 person-times were screened for echinococcosis among residents at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 094 residents detected with cystic echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ² = 358.602, P < 0.001). A total of 32 931 person-times were screened for echinococcosis among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 296 children detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ² = 267.673, P < 0.001). A total of 33 230 domestic dog stool samples were tested for Echinococcus coproantigens in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 777 Echinococcus coproantigens-positive samples tested, and the positive rate of Echinococcus coproantigens appeared a tendency towards a decline in domestic dogs over years (χ² = 2 210.428, P < 0.001), while the positive rate of Echinococcus coproantigens showed a tendency towards a rise in domestic animals from 2016 to 2022 (χ² = 37.745, P < 0.001). The positive rate of Echinococcus coproantigens remained relatively stable in stray dogs in Tianzhu Tibetan Autonomous County, Gansu Province from 2019 to 2022 (χ² = 0.315, P = 0.575). A total of 10 973 sheep were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2007 to 2022, with 334 sheep detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a decline in sheep over years (χ² = 53.579, P < 0.001); however, there was no significant change in the detection of echinococcosis during the period from 2015 through 2022 (χ² = 1.520, P = 0.218). A total of 2 400 cattle were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2017 to 2022, with 231 cattle detected with echinococcosis, and the detection of echinococcosis showed a tendency towards a decline over years (χ² = 5.579, P < 0.05). The awareness of echinococcosis control knowledge increased from 44.37% in 2007 to 94.00% in 2022 among residents at ages of 12 years and older and from 52.50% in 2007 to 92.50% in 2022 among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, respectively. Conclusions There has been a reduction in the detection of echinococcosis in humans and domestic animals and the positive rate of Echinococcus coproantigens in dogs and a rise in the awareness of the echinococcosis control knowledge following the implementation of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province; however, integrated echinococcosis control measures are still required for further control of the prevalence of echinococcosis.

Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.

Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the sacroiliac joints, spine and peripheral joints. In China, standardized diagnosis and treatment of AS is still to be popularized. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed standardization of diagnosis and treatment of AS. The purposes are: (1) to standardize the diagnosis and evaluation of AS; (2) to promote rational use of non-steroidal anti-inflammatory drugs, biological as well as traditional disease modifying anti-rheumatic drugs, so as to improve the patient′s quality of life.

Hemophilia B is a genetic disorder caused by coagulation factor Ⅸ(FⅨ) deficiency, mainly manifesting as joint, muscle and deep tissue bleeding. Hemophilia pseudotumor is a mass formed by soft tissue liquefaction and necrosis caused by repeated bleeding. Most pseudotumors occur in the bone and muscle. We report a case of hemophilia B with pseudotumor formation in the pelvis and abdomen, where lesion location is relatively rare. After active and effective hemostasis, the patient's hematuria symptom gradually improved. This case suggests that early and timely hemostatic treatment is crucial for patients with hemophilia.

Objective To evaluate the predictive values of serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, serum cystatin C (Cys-C) and serum creatinine (Scr) for early delayed graft function (DGF) in kidney transplant recipients. Methods Clinical data, blood and urine samples of 159 kidney transplant recipients were collected. All recipients were divided into the DGF group (n=42) and immediate graft function (IGF) group (n=117) according to the incidence of DGF. Clinical data of all recipients were analyzed. The changes of serum NGAL, urine NGAL, Cys-C and Scr levels were statistically compared between two groups. The predictive values of different markers for early DGF were assessed. Results Among 159 kidney transplant recipients, DGF occurred in 42 cases with an incidence rate of 26.4%. There were statistically significant differences in donor age, cold ischemia time of donor kidney and complement-dependent cytoxicity (CDC) between the two groups(all P < 0.05). Within postoperative 2 weeks, the serum NGAL levels in the DGF group were higher than those in the IGF group (all P < 0.05). The Cys-C, Scr and urine NGAL levels in the DGF group were higher compared with those in the IGF group within 3 weeks after kidney transplantation(all P < 0.001). Serum NGAL, urine NGAL, Cys-C and Scr levels had certain predictive values for early DGF in kidney transplant recipients. Cys-C yielded the highest predictive value with a cut-off value of 4.73 mg/L, sensitivity of 0.833, specificity of 0.812 and area under the curve (AUC) of 0.895. Conclusions Cys-C has higher predictive value for early DGF in kidney transplant recipients compared with serum NGAL, urine NGAL and Scr.

Objective:To analyze the characteristics of viral isolation and unique recombinant from untreated HIV-1 patients infected through sexual transmission and injection drug use, so as to provide evidence for understanding the biological characteristics and precise prevention and control of HIV-1 infection in different transmission routes.Methods:In view of the different HIV-1 transmission risks, newly diagnosed untreated HIV-1 patients from Beijing, Guangxi and Sichuan were carefully selected. Venous blood was collected to detect the viral load and CD4 + T cell count, and peripheral blood lymphocytes were isolated for virus isolation. Viral RNAs were extracted from the virus supernatant, and the near full-length genome sequences were obtained using in-house method, then the recombination patterns were determined. Results:Among the 65 HIV-1 infection, 32(49.2%), 20(30.8%) and 13(20.0%) were infected via men who have sex with men (MSM), heterosexual and injection drug use (IDU), respectively; genotypes mainly included 26(40.0%) CRF07_ BC, 23(35.4%) CRF01_ AE, and 9(13.8%) unique recombinant types (URFs). A total of 46 HIV-1 clinical strains were isolated. The positive rate of HIV-1 isolation was significantly negatively correlated with CD4 + T cells ( X2=4.22, P=0.04), but positively correlated with viral load ( X2=22.4, P<0.001); the multi-variate generalized estimating equations(GEE) model analysis of HIV-1 P24 antigen content showed similar result. In addition, GEE model showed a positive correlation between viral P24 antigen content and virus-producing culture time (52.14, 95% CI: 9.42~94.87, P=0.017). Viral growth curve analysis showed that the level of viral P24 antigen in MSM Group was significantly higher than that in heterosexual group and IDU group (adjusted P values were p<0.01 and P<0.05, respectively), on the 14th day after culture. The proportion of URFs in MSM Group was higher than that in heterosexual group, and the recombinant breakpoints in MSM Group were more than that in heterosexual group. Conclusions:MSM population was more sensitive to HIV-1 virus isolation; there was unique diversity of recombinant forms of HIV-1 among those with sexually transmitted infections, especially in the MSM population.