microRNA-26a inhibits extracellular matrix synthesis in high glucose-induced renal tubular epithelial cells by regulating ferroptosis / 安徽医科大学学报

Objective To investigate the effect and possible mechanism of microRNA-26a(miR-26a)on the syn-thesis of extracellular matrix(ECM)induced by high glucose(HG)in renal tubular epithelial cells(RTECs).Methods A model of diabetic kidney disease(DKD)was constructed by inducing RTECs with HG.MiR-26a was overexpressed in HG-induced RTECs,and RT-qPCR and Western blot were used to assess the effects of miR-26a on ECM synthesis and ferroptosis-related markers in HG-treated RTECs.Ferrostatin(Fer-1)was used to inhibit ferroptosis in the DKD model,and its impact on ECM synthesis was evaluated.RT-qPCR and Western blot were performed to measure ferroptosis-related markers,and fluorescence microscopy was used to observe the intensity of reactive oxygen species(ROS).Results Compared with the control group,the expression of miR-26a decreased in HG-treated cells,while the expression levels of ECM synthesis-related indexes fibronectin and collagen Ⅰ in-creased.After overexpressing miR-26a,the HG+miR-26a group showed a significant increase in miR-26a expres-sion and a decrease in fibronectin and collagen Ⅰ expression compared to the HG group.In terms of ferroptosis,the protein and mRNA expression of SLC7A11 and GPX4 significantly decreased,the expression of TFR-1 and AC-SL4 significantly increased,and the fluorescence intensity of ROS was significantly enhanced in the HG group com-pared with the control group.Inhibition of ferroptosis in the HG+Fer-1 group resulted in significant changes in fer-roptosis and ECM synthesis-related indicators expression levels compared to the HG group.Furthermore,re-expres-sion of miR-26a in the HG+miR-26a led to significant changes in ferroptosis-related indicators expression levels and decreased ROS fluorescence intensity compared to the HG group.Conclusions In HG-induced RTECs,miR-26a inhibits the occurrence of ferroptosis,thus reducing ECM synthesis.

Finite element analysis of medial patellofemoral ligament reconstruction at different flexion angles / 中国组织工程研究

BACKGROUND:The medial patellofemoral ligament reconstruction is the most commonly used method for the treatment of lateral dislocation of patella at present.The ultimate goal is to adjust the patella to the normal anatomical position and restore the patella track.Currently,the main core problem of medial patellofemoral ligament reconstruction is the selection of its femoral end fixation point. OBJECTIVE:Finite element method was used to analyze the limiting effect of the reconstructed medial patellofemoral ligament on the patella at different flexion angles of the knee joint,and to simulate the limiting effect of medial patellofemoral ligament reconstruction at different fixation points of the femoral end on the patellofemoral end,so as to provide help for the selection of fixation points of the femoral end during the reconstruction of the medial patellofemoral ligament. METHODS:A finite element model of knee including bone and soft tissue was established according to the extracted CT and MRI data of knee joint.When the knee flexion angle of 30° and 60° was simulated,the medial patellofemoral ligament was constructed by selecting different fixation points of femur end.The contact stress and contact area between patellofemoral joints at different points were compared,as well as the transverse binding force on patella.The equilength of the medial patellofemoral ligament constructed from the same fixation point of the femoral end at different flexion angles was verified to study the effect of various reconstruction positions of the medial patellofemoral ligament. RESULTS AND CONCLUSION:(1)A three-dimensional finite element model of the knee joint at 30° and 60° flexion angles was established to construct the medial patellofemoral ligament at different fixation points of the femur end.The medial patellofemoral ligament constructed at the same position of the femur end had usable isometric length at different flexion angles.(2)After the lateral displacement of the patella,in the transverse direction,the medial patellofemoral ligament constructed at different fixed points of the femur end produced different transverse binding force on the patella,and the transverse binding force was maximum at the anterior 10 mm and minimum at the proximal 5 mm.In the longitudinal direction,the location and size of stress concentration points on the patella cartilage were roughly the same,and the contact pressure did not change much.However,the contact area between the patella cartilage and the femoral cartilage was significantly different,with the maximum contact area at 10 mm at the front end and the minimum contact area at 5 mm at the proximal end.(3)The medial patellofemoral ligament constructed at the center of the saddle region has a good lateral restriction on the patella,but does not cause excessive restriction on the patella in the longitudinal restriction,and can achieve a good restriction on the patella.

Finite element analysis of talus cartilage before and after anterior talofibular ligament injury / 中国组织工程研究

BACKGROUND:The injury of the anterior talofibular ligament is most common in joint ligament injuries.The use of the finite element method to simulate ankle joint motion has the advantages of short experimental time,complex boundary conditions that can be simulated,and mechanical properties. OBJECTIVE:To analyze the effect of the anterior talofibular ligament on the stress distribution of the talus trochlea and the stability of the ankle joint. METHODS:A finite element model of the ankle was established based on CT and MRI images of patients with anterior talofibular ligament injury who were followed up for two months after Brostr?m surgery to simulate ankle joint stress in patients with anterior talofibular ligament injury before and after surgery during normal gait cycles(ground phase,neutral phase,and off-ground phase).The stress distribution and maximum stress value of the talus bone cartilage were measured before and after surgery,and their differences were analyzed. RESULTS AND CONCLUSION:Under normal gait,the anterior talofibular ligament has a certain protective effect on the talus trochlea in any position,reducing the wear of the ankle joint on the talus trochlea during movement.In all three phases,stress concentration was observed on the surface of the talus trochlea near the inner side of the ankle joint.The influence of the anterior talofibular ligament on the stability of the talus trochlear is much greater in the off-ground phase than in the ground phase and neutral phase.Under certain circumstances,the greater the torque on the ankle joint,the more significant the effect of the anterior talofibular ligament on the stability of the talus trochlea.

Application value of combined coagulation function indicators in monitoring hypercoagulable state of patients with colorectal cancer after chemotherapy / 中国癌症杂志

Background and purpose:The plasma used for routine coagulation test(CCT)can only reflect a single component at a certain coagulation time point/segment,while thromboelastography(TEG)can depict the overall dynamic process curve of coagulation and fibrinolysis,which can more independently and completely reflect the true state of the blood and can serve as a supplement to coagulation function testing.This study aimed to evaluate the application value of combined coagulation function indexes in monitoring the hypercoagulable state of patients with colorectal cancer after chemotherapy,and to explore the risk factors of thrombosis in patients with colorectal cancer after chemotherapy,so as to provide reference for clinical monitoring of hypercoagulable state.Methods:A total of 160 patients with colorectal cancer from Fudan University Shanghai Cancer Center from June 2021 to June 2023 were selected as the experimental group,and 80 healthy subjects were selected as the control group.Then the experimental group was divided into a group without thrombosis(82 cases)and a group with thrombosis(78 cases)according to whether they had thrombosis or not.The determinations of thromboelastography(TEG)[coagulation reaction time(R),coagulation formation time(K),blood clot formation rate(α-Angle),maximum amplitude(MA)and coagulation index(CI)],conventional coagulation tests(CCT)[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(Fib),D-dimer(DD),fibrinogen degradation products(FDP)]and platelet count(PLT)were studied among three groups.With or without thrombosis as the criterion of hypercoagulable state,statistically significant indicators were selected to be included in the binary logistic regression analysis,and the receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of single and combined detection of the coagulation function indicators for hypercoagulable state in patients with colorectal cancer after chemotherapy.Basic information,tumor stage and Autar score of deep vein thrombosis were collected in 160 patients with colorectal cancer.Logistic regression analysis was performed to explore the risk factors of thrombosis.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(number:050432-4-2108*).Results:Compared with the control group,the R,TT and PLT of the group with thrombosis were decreased(P＜0.05),while APTT,PT,DD and FDP were increased(P＜0.05).The differences in various indicators between the group with thrombosis and the control group were statistically significant(P＜0.05).Compared with the group without thrombosis,the K in the group with thrombosis decreased(P＜0.05),while Angle,MA,CI,FIB,DD and FDP all increased(P＜0.05).ROC curve analysis showed that in the assessment of hypercoagulable state in patients with colorectal cancer after chemotherapy,the area under curve(AUC)of TEG was 0.756,sensitivity was 67.5%,and specificity was 73.8%.The AUC of CCT was 0.691,sensitivity was 78.8%,and specificity was 56.2%.The combined detection AUC was 0.840,sensitivity was 80.0%,and specificity was 77.5%.In the analysis of risk factors,tumor stage,distant metastasis and Autar score were correlated with thrombus formation in patients with colorectal cancer after chemotherapy(P＜0.05),and the differences of the three risk factors in K,Angle,MA,CI,Fib,DD and FDP were statistically significant(P＜0.05).Conclusion:K,Angle,MA,CI,Fib,DD and FDP are the main indicators to reflect the hypercoagulable state,and the combined detection of TEG and CCT can better reflect the coagulation state of patients with colorectal cancer after chemotherapy.Tumor stage Ⅲ to Ⅳ,distant metastasis and high Autar score are risk factors for thrombosis.The incidence of thrombosis can be reduced by monitoring the relevant coagulation indicators in the high-risk population.

Study on the toxicity characteristics of a clinical bloodstream isolate of Salmonella Telelkebir / 中国人兽共患病学报

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Research progress of ICU-acquired weakness / 中华危重病急救医学

ICU-acquired weakness (ICU-AW) is a common complication in the intensive care unit (ICU). The occurrence of ICU-AW directly leads to prolonged ICU stays for critically ill patients, and in severe cases, it continues to affect their quality of life even after discharge. This article provides a comprehensive review of the research progress on ICU-AW based on domestic and foreign studies, aiming to provide a scientific overview of ICU-AW, including its definition, pathophysiology, diagnosis, screening tools, influencing factors, and potential intervention strategies, so as to promote timely planning and implementation of relevant screening and intervention measures.

Separable Reversible Data Hiding in Encrypted Images for Remote Sensing Images.

High security and effectiveness are critical performance metrics in the data transmission process for satellite remote sensing images, medical images, and so on. Previously, the receiver could gain a high-quality cover image (lossy) after decryption in a separable manner to balance embedding capacity (EC) and security. Completely separable, reversible data hiding in encrypted image (SRDH-EI) algorithms are proposed to address this issue. In this study, the cover image was preprocessed at the sender's end. The pre-embedded pixels and most significant bits (MSB) were compressed via two coding methods to reserve space. Additionally, the header data were embedded for marking. Finally, auxiliary data and secret data were embedded in a forward "Z" and reverse "Z" shape before and after encryption, respectively. The receiver could extract secret data and decrypt the cover image separately using the keys and markers. The experimental results demonstrate that the algorithm reached a high EC for remote sensing images by utilizing pixel correlation at multiple positions within the groups. The cover image could maintain its entropy during the data embedding process, ensuring security. The decrypted image could be recovered without distortion, furthermore, the receiver could achieve complete separability, so it has good application prospects for remote sensing images.

Clinicopathological features of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Analyses on employment of clinical medical students of eight-year program and its implications to talent cultivation / 中华医学教育探索杂志

Objective:To analyze employment status and its tendency of eight-year program clinical medical graduates and explore its implications to talent cultivation using employment data from a university in Beijing.Methods:Descriptive analysis was used in this study. Indicators that were analyzed included quantity of employment, employment rate, employment region and specialty.Results:Between 2009 and 2021, a total of 2 281 eight-year clinical medical students graduated in the university. Among them, 2 188 (96.0%) of them were employed in the year of graduation. On average, 90.8% (2 034/2 241) of them were employed by medical institutions although the percentage decreased over years. A majority of them chose to work in economically developed provinces of eastern China. Those chose to work in Beijing accounted for 78.7% (1 723/2 188), the highest percentage among all provinces. The top two specialties of choice were surgery and internal medicine, which respectively accounted for 33.0% (753/2 281) and 24.4% (557/2 281). Only a few of them chose to study some specialties that were challenged by a serious shortage of physicians, including pediatrics, mental diseases and mental health.Conclusion:Although the employment status of eight-year clinical medical graduates are good, it is still necessary to pay attention to the new tendency of employment, and further improve training scheme. Meanwhile, more guidance on choice of secondary specialties are needed to build a competent talent team for specialty development. Finally, education of curriculum iedology and politics should be strengthened to encourage them to work in specialties and remote provinces that face a serious shortage of physicians.

Preliminary study on the value of fetal MRI lung volume and mediastinal shift angle for predicting prognosis of left congenital diaphragmatic hernia / 中华放射学杂志

Objective:To explore the value of fetal lung volume and mediastinal shift angle (MSA) based on fetal MRI in predicting the prognosis of congenital diaphragmatic hernia (CDH).Methods:Fetuses with left CDH that did fetal MRI in Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine from September 2016 to January 2022 were retrospectively collected. There were 65 patients, and their gestational age was 29 (26, 35) weeks when they were diagnosed with left CDH by MRI. Observed fetal lung volume and MSA were measured based on fetal MRI, and observed/expected lung volume (o/eFLV) based on gestational age was calculated. The clinical data were collected from birth to discharge, and patients were divided into survival group and death group in case of prognosis at discharge, with 54 cases in the survival group and 11 cases in the death group. The student′s t test was used to compare the difference of o/eFLV and MSA between the survival group and the death group, and the receiver operating characteristic (ROC) curve was used to evaluate the value of o/eFLV and MSA in predicting the prognosis of left CDH. Results:The o/eFLV of the survival group was 51.5%±18.3%, higher than that of the death group (27.8%±4.4%), and the difference was significant ( t=8.29, P<0.001). The MSA of the survival group was 33.1°±1.2°, lower than that of the death group (41.8°±2.7°), and the difference was significant ( t=-11.15, P<0.001). The area under the ROC curve (AUC) of o/eFLV to predict the fetal survival or death was 0.939 (95%CI 0.851-0.983), the cutoff value was 33.8%, the sensitivity was 100%, the specificity was 88.9%. The AUC of MSA was 0.998 (95%CI 0.941-1.000), the cutoff value was 37.2°, the sensitivity was 100%, the specificity was 98.2%. Conclusions:The o/eFLV and MSA that were measured based on fetal MRI can effectively predict the fetus′s prognosis with left CDH.

Analysis on the vaccination coverage of 13-valent pneumococcal conjugate vaccine in China from 2017 to 2021 / 中华预防医学杂志

Objective: To explore the vaccination coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) in China from 2017 to 2021. Methods: Using the reported number of PCV13 administrated doses from 2017 to 2021 and the population data from 31 provinces in China, which were collected by the Immunization Program Information System and summarized data at different levels (prefecture, provincial, and national). Collecting batch release data of PCV13 during the same period through the official website of the National Institutes for Food and Drug Control. The average coverage level of PCV13 was calculated by comparing the number of PCV13 vaccinations reported annually to the number of births in that year, and the spatial auto-correlation analysis was conducted in 2021 at the prefecture level. The coverage of PCV13 vaccination was estimated by the total vaccine doses administered each year divided by the number of newborn in the year, as of the administrated dose number per 100 people. Results: From March 2017 to December 2020, the total batch release of PCV13 was 20.06 million, with a total of 71.54, 384.75, 475.45, and 10.8886 million doses each year. During the same period, PCV13 reported doses were 20.2369 million and the vaccination doses from 2017 to 2021 were 4.08, 170.46, 407.52, 599.77, and 8.4185 million doses, respectively. From 2017 to 2021, the ratio of PCV13 doses administrated per 100 infants in each year was 0.25, 10.26, 23.81, 38.16, and 69.90 doses per 100 people, respectively. The range of the ratio in each province increased from 3.85 doses in 2017 to 264.41 doses per 100 people in 2021. The spatial auto-correlation analysis results showed that based on prefecture-level cities, there was spatial clustering in a certain area of PCV13 coverage from 2017 to 2021, and the spatial correlation in 2021 was the highest. The hotspot analysis showed that the hotspot areas with high coverage levels of PCV13 were concentrated in Jiangsu, Zhejiang, Shanghai, Fujian and their surrounding areas. The cold spots with low vaccine coverage were concentrated in Yunnan, Qinghai, Tibet, and their surrounding areas. Conclusion: The average coverage level of PCV13 is low in China with significant regional differences.

Analysis on the vaccination coverage of 13-valent pneumococcal conjugate vaccine in China from 2017 to 2021 / 中华预防医学杂志

Objective: To explore the vaccination coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) in China from 2017 to 2021. Methods: Using the reported number of PCV13 administrated doses from 2017 to 2021 and the population data from 31 provinces in China, which were collected by the Immunization Program Information System and summarized data at different levels (prefecture, provincial, and national). Collecting batch release data of PCV13 during the same period through the official website of the National Institutes for Food and Drug Control. The average coverage level of PCV13 was calculated by comparing the number of PCV13 vaccinations reported annually to the number of births in that year, and the spatial auto-correlation analysis was conducted in 2021 at the prefecture level. The coverage of PCV13 vaccination was estimated by the total vaccine doses administered each year divided by the number of newborn in the year, as of the administrated dose number per 100 people. Results: From March 2017 to December 2020, the total batch release of PCV13 was 20.06 million, with a total of 71.54, 384.75, 475.45, and 10.8886 million doses each year. During the same period, PCV13 reported doses were 20.2369 million and the vaccination doses from 2017 to 2021 were 4.08, 170.46, 407.52, 599.77, and 8.4185 million doses, respectively. From 2017 to 2021, the ratio of PCV13 doses administrated per 100 infants in each year was 0.25, 10.26, 23.81, 38.16, and 69.90 doses per 100 people, respectively. The range of the ratio in each province increased from 3.85 doses in 2017 to 264.41 doses per 100 people in 2021. The spatial auto-correlation analysis results showed that based on prefecture-level cities, there was spatial clustering in a certain area of PCV13 coverage from 2017 to 2021, and the spatial correlation in 2021 was the highest. The hotspot analysis showed that the hotspot areas with high coverage levels of PCV13 were concentrated in Jiangsu, Zhejiang, Shanghai, Fujian and their surrounding areas. The cold spots with low vaccine coverage were concentrated in Yunnan, Qinghai, Tibet, and their surrounding areas. Conclusion: The average coverage level of PCV13 is low in China with significant regional differences.

Study on ameliorative effect of IDHP on excessive fat accumulation in hepatocytes / 中国药理学通报

Aim To explore whether isopropyl3-(3, 4-dihydroxyphenyl) -2-hydroxypropanoate (IDHP) could inhibit fat accumulation in liver cells by improving mitochondrial function, and alleviate the symptom of excessive fat accumulation in patients with NAFLD. Methods Cell steatosis model was established by inducing hepatocyte fat accumulation using palmitic acid and oleic acid (PA: OA molar ratio =1

Epidemiological distribution of genotypes and sub-genotypes of hepatitis B virus in 15 ethnic groups in China / 中华流行病学杂志

Objective: To understand the distribution of genotypes and sub-genotypes of HBV in different ethnic groups in China. Methods: The HBsAg positive samples were selected by stratified multi-stage cluster sampling from the sample base of national HBV sero-epidemiological survey in 2020 for the amplification of S gene of HBV by nested PCR. A phylogeny tree was constructed to determine the genotypes and sub-genotypes of HBV. The distribution of genotypes and sub-genotypes of HBV were analyzed comprehensively by using laboratory data and demographic data. Results: A total of 1 539 positive samples from 15 ethnic groups were successfully amplified and analyzed, and 5 genotypes (B, C, D, I and C/D) were detected. The proportion of genotype B was higher in ethnic group of Han (74.52%, 623/836), Zhuang (49.28%, 34/69), Yi (53.19%, 25/47), Miao (94.12%, 32/34), Buyi (81.48%, 22/27). The proportions of genotype C were higher in ethnic groups of Yao (70.91%, 39/55). Genotype D was the predominant genotype in Uygur (83.78%, 31/37). Genotype C/D were detected in Tibetan (92.35%,326/353). In this study, 11 cases of genotype I were detected, 8 of which were distributed in Zhuang nationality. Except for Tibetan, sub-genotype B2 accounted for more than 80.00% in genotype B in all ethnic groups. The proportions of sub-genotype C2 were higher in 8 ethnic groups, i.e. Han, Tibetan, Yi, Uygur, Mongolian, Manchu, Hui and Miao. The proportions of sub-genotype C5 were higher in ethnic groups of Zhuang (55.56%, 15/27) and Yao (84.62%, 33/39). For genotype D, sub-genotype D3 was detected in Yi ethnic group and sub-genotype D1 was detected in both Uygur and Kazak. The proportions of sub-genotype C/D1 and C/D2 in Tibetan were 43.06% (152/353) and 49.29% (174/353). For all the 11 cases of genotype I infection, only sub-genotype I1 was detected. Conclusions: Five genotypes and 15 sub-genotypes of HBV were found in 15 ethnic groups. There were significant differences in the distribution of genotypes and sub-genotypes of HBV among different ethnic groups.

Acupuncture for Patients with Chronic Spontaneous Urticaria: A Randomized, Sham-Controlled Pilot Trial / 中国结合医学杂志

OBJECTIVE@#To determine the feasibility of conducting a full-scale randomized controlled trial (RCT) and investigate the basic information and safety of acupuncture for patients with chronic spontaneous urticaria (CSU).@*METHODS@#A total of 80 participants with CSU from July 2018 to July 2019 were randomly assigned to receive active acupuncture (n=41) on a fixed prescription of acupoints or sham acupuncture (n=39) with superficial acupuncture on non-acupuncture points through the completely randomized design. Patients in both groups received 5 sessions per week for 2 weeks, and participants were followed for a further 2 weeks. Feasibility was assessed by recruitment and randomization rates, retention of participants, treatment protocol adherence, and the incidence of adverse events (AEs). The clinical primary outcome was the changes from baseline weekly urticaria activity scores (UAS7) after treatment at 2 weeks. Secondary outcomes included the Visual Analogue Scale (VAS) score of itching intensity, Dermatology Life Quality Index (DLQI), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA).@*RESULTS@#A total of 80 participants were enrolled. The recruitment rate of 24.02%, randomization rate of 100%, a loss rate of 6.25%, and no obvious AEs were observed in either group. The decrease from baseline in the mean UAS7 total score at week 2 in the active acupuncture group was -8.63 (95%CI, -11.78 to -5.49) and -6.21 (95%CI, -9.43 to -2.98) in the sham acupuncture group for a between-group difference of -2.42 (95% CI, -6.93 to 2.07). The change in the DLQI, VAS of itching intensity, HAMA, and HAMD were a slightly better improvement trend in the active acupuncture group than the sham acupuncture group, but the between-group difference was not significant.@*CONCLUSIONS@#Active acupuncture had a better improvement trend in alleviating symptoms, improving quality of life and regulating the mood of anxiety and depression in patients with CSU than sham acupuncture. (Registration Nos. AMCTR-ICR-18000190 and ChiCTR2100054776).

Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia / 中国结合医学杂志

OBJECTIVE@#To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI).@*METHODS@#First, the target genes of THP and AMI were collected from SymMap Database, Traditional Chinese Medicine Database and Analysis Platform, and Swiss Target Prediction, respectively. Then, the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally, the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR in vivo and in vitro.@*RESULTS@#MMP9, PPARG, PTGS2, SLC6A4, ESR1, JAK2, GSK3B, NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function, as well as alleviated myocardial cell damage. Furthermore, THP significantly decreased the RNA expression levels of MMP9, PTGS2, SLC6A4, GSK3B and ESR1 (P<0.05, P<0.01) after AMI. In vitro, THP significantly increased H9C2 cardiomyocyte viability (P<0.05, P<0.01) and inhibited the RNA expression levels of PPARG, ESR1 and AR (P<0.05, P<0.01) in OGD model.@*CONCLUSIONS@#THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation, the improvement of energy metabolism and the regulation of hormones.

Challenges to global pertussis prevention and control / 中华流行病学杂志

Pertussis is an acute, highly infectious respiratory disease caused by Bordetella pertussis, and is one of the leading causes of infant disease and death worldwide. The pertussis vaccine has been used in the expanded program on immunization globally since 1974 and the vaccination coverage remains high. In recent years, the pertussis incidence rate increased, even pertussis outbreaks occurred, in more and more countries or areas after years with low incidence level. The disease burden of pertussis has been seriously underestimated, and the prevention and control of pertussis is facing many challenges. This article reviews the epidemic status of pertussis worldwide, the factors affecting the reemergence of pertussis, and the challenges in the prevention and control to provide a reference for prevention and control of pertussis.

Vitamin C is an efficient natural product for prevention of SARS-CoV-2 infection by targeting ACE2 in both cell and in vivo mouse models

ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2s binding, how to efficiently and flexibly control ACE2 levels for prevention of SARS-CoV-2 infection has not been explored. Here, we revealed Vitamin C (VitC) administration as an effective strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in a dose-dependent manner, while partial reduction of ACE2 can greatly restrict SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination at Lys788 and degradation of ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC administration reduced host ACE2 and largely blocked SARS-CoV-2 infection in mice. This study identified an in vivo ACE2 balance controlled by both USP50 and an essential nutrient VitC, and revealed a critical role and application of VitC in daily protection from SARS-CoV-2 infection. HighlightsO_LIVitC reduces ACE2 protein levels in a dose-dependent manner C_LIO_LIVitC and USP50 regulate K48-linked ubiquitination at Lys788 of ACE2 C_LIO_LIVitC blocks the interaction between USP50 and ACE2 C_LIO_LIVitC administration lowers host ACE2 and prevents SARS-CoV-2 infection in vivo C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/499651v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@196682borg.highwire.dtl.DTLVardef@190f14dorg.highwire.dtl.DTLVardef@d22b59org.highwire.dtl.DTLVardef@1c0faa_HPS_FORMAT_FIGEXP M_FIG C_FIG The deubiquitinase USP50 controls ACE2 protein stability and levels, while Vitamin C blocks the USP50-ACE2 interaction and therefore results in ACE2 degradation, offering a flexible and efficient approach to protection of the host from SARS-CoV-2 infection.

Heterologous CoronaVac plus Ad5-nCOV versus homologous CoronaVac vaccination among elderly: a phase 4, non-inferiority, randomized study

ImportancePeople over 60 developed less protection after two doses of inactivated COVID-19 vaccine than younger people. Heterologous vaccination might provide greater immunity and protection against variants of concern. ObjectiveTo assess the safety and immunogenicity of a heterologous immunization with an adenovirus type 5-vectored vaccine (Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) previously. DesignAn observer-blind, randomized (1:1) trial, conducted from August 26 to November 13, 2021. SettingA single center in Jiangsu Province, China. Participants299 participants aged 60 years and older, of them 199 primed with two doses of CoronaVac in the past 3-6 months and 100 primed with one dose of CoronaVac in the past 1-2 months. InterventionConvidecia or CoronaVac as boosting dose Main Outcomes and MeasuresGeometric mean titers (GMTs) of neutralizing antibodies against wild-type SARS-CoV-2, and Delta and Omicron variants 14 days post boosting, and adverse reactions within 28 days. ResultsIn the three-dose regimen cohort (n=199; mean (SD) age, 66.7 (4.2) years; 74 (37.2%) female), 99 and 100 received a third dose of Convidecia (group A) and CoronaVac (group B), respectively. In the two-dose regimen cohort (n=100; mean (SD) age, 70.5 (6.0) years; 49 (49%) female), 50 and 50 received a second dose of Convidecia (group C) and CoronaVac (group D), respectively. GMTs of neutralizing antibodies against wild-type SARS-CoV-2 at day 14 were 286.4 (95% CI: 244.6, 335.2) in group A and 48.2 (95% CI: 39.5, 58.7) in group B, with GMT ratio of 6.2 (95% CI: 4.7, 8.1), and 70.9 (95% CI: 49.5, 101.7) in group C and 9.3 (95% CI: 6.2, 13.9) in group D, with GMT ratio of 7.6 (95% CI: 4.1, 14.1). There was a 6.3-fold (GMTs, 45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralizing antibodies against Delta and Omicron variants in group A, respectively, compared with group B. However, there was no significant difference between group C and group D. Both heterologous and homologous booster immunizations were safe and well tolerated. Conclusions and RelevanceHeterologous prime-boost regimens with CoronaVac and Convidecia induced strong neutralizing antibodies in elderly, which was superior to that induced by the homologous boost, without increasing safety concerns. Trial RegistrationClinicalTrials.gov NCT04952727 Key Points QuestionDoes a heterologous immunization with recombinant adenovirus type 5-vectored vaccine (Convidecia) produced a non-inferior or superior response of neutralizing antibodies among elderly primed with two doses of inactivated COVID-19 vaccine (CoronaVac), compared to the homologous boosting FindingsIn this randomized clinical trial, a heterologous third dose of Convidecia resulted in a 6.2-fold (geometric mean titers: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralizing antibodies against wild-type strain, Delta and Omicron variants 14 days post boosting, respectively, compared to the homologous boost with CoronaVac MeaningHeterologous prime-boost regimens with CoronaVac and Convidecia induced strong neutralizing antibodies in elderly, which was superior to that induced by the homologous boosting.