Clinical efficacy of Buzhong Yiqi decoction in the treatment of hospital-acquired pneumonia with multi-drug resistant bacteria: a prospective, randomized, multicenter controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Buzhong Yiqi decoction (, BZYQ) in the treatment of hospital-acquired pneumonia (HAP) with multi-drug-resistant bacteria (MDRB). METHODS: This 28-day study was conducted at 5 clinical centers in Shanghai. The eligible patients were randomly assigned (1:1) into the intervention group (BZYQ plus conventional Western Medicine therapy) and control group (conventional Western Medicine therapy). The primary outcomes were the clinical response, clinical pulmonary infection score (CPIS), and microbiologic response. The secondary outcomes were the 28-day all-cause mortality (ACM), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, ventilator weaning rate, length of mechanical ventilation (MV), length of hospital stay, and changes of infection indicators. RESULTS: Altogether 83 subjects in the intervention group and 85 subjects in the control group were analyzed. The clinical success rate (48.2%) and the pathogen eradication rate (59.0%) of the intervention group were all better than those of the control group (32.9% and 38.9%, respectively) with statistically significant differences (<0.05). The CPIS score of the intervention group (8.9 ± 1.7) was lower than that of the control group (9.6 ± 2.5) (<0.05). The length of MV in the intervention group [(13.7 ± 6.4) d] was significantly shorter than that of the control group [ (17.2 ± 7.2) d] (<0.05). The 28-day ACM of the intervention group (13.33%) was lower than that of the control group (21.2%) with no statistically significant difference (>0.05). The differences between two groups in ventilator weaning rate, length of hospital stay, and APACHE Ⅱ score were not statistically significant (> 0.05). The intervention group displayed decreases in white blood cell count, C-reactive protein, neutrophil percentage, and procalcitonin at day 28 compared with baseline (<0.05). No serious adverse events occurred in either group during the 28-day follow-up. CONCLUSION: BZYQ may be an effective therapeutic option for the management of HAP with MDRB.

Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study / 中华妇产科杂志

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.

Efficacy and Safety of Huashi Baidu Granules in Treating Patients with SARS-CoV-2 Omicron Variant: A Single-Center Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.@*METHODS@#A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users).@*RESULTS@#The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study.@*CONCLUSION@#HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).

Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC / 中国肺癌杂志

BACKGROUND@#Programmed cell death protein 1 (PD-1) combined with platinum containing dual drug chemotherapy is a new adjuvant treatment option for operable stage III non-small cell lung cancer (NSCLC), and the quality assurance of clinical trials of related drugs plays a crucial role in the results of the clinical trials. This study aims to explore the impact of adverse events (AEs) supervision on reducing treatment-related AEs in patients.@*METHODS@#66 NSCLC patients admitted to Shanghai Chest Hospital from July 2020 to October 2021 were prospectively collected. All the patients received 3 cycles of neoadjuvant treatment of Camrelizumab in combination with Docetaxel and Cisplatin. 4 weeks-6 weeks after neoadjuvant therapy, the patients accepted surgical treatment. One cycle of postoperative adjuvant treatment was given within 30 days after surgery, and 3 weeks after the completion of postoperative adjuvant treatment, Camrelizumab consolidation treatment was intiated, with a total of 13 cycles. The quality of life-C30 (QoL-C30) was used to measure patients' quality of life and the occurrence of AEs was monitored.@*RESULTS@#The overall safety is good, with a total of 300 AEs occurring in 66 patients, including 282 cases of grade 1-2 AEs and 18 cases of grades 3-4 AEs. The most common grades 3-4 AEs associated with PD-1 antibodies occurred in 6 cases (9.1%). Neoadjuvant therapy supervision can lead to a decrease in patients' QOL-C30 scores (P<0.05) and an improvement in their quality of life.@*CONCLUSIONS@#Camrelizumab combined with Docetaxel and Cisplatin can be used as a new adjuvant treatment for operable stage III NSCLC. Through the observation and control of AEs, treatment measures can be taken in time to reduce further complications, ensure patient' safety, and ensure the authenticity, scientificity and reliability of clinical trial data.

Retrospection and reflection on standardized residency training system from the perspective of medical education history / 中华医学教育探索杂志

Based on the national policies, regulations and documents on residency training, this paper sorts out the historical evolution of the standardized residency training system in China, and divides its development into four stages: preliminary exploration, local pilot, national trials, and implementation. It also puts forward some practical thoughts on its development law and future trend, such aspects as that the system reform follows the top-down administrative order and indicative plan, the system pays attention to the gradual implementation on the basis of summing up practical experience, and the system needs continuous implementation and improvement from the overall perspective.

Drug-induced dysphagia risk in elder people——A pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) database / 中国临床药理学与治疗学

AIM: To evaluate the risk of drug-related dysphagia in elder people based on the FDA Adverse Event Reporting System (FAERS). METHODS: We collected the reports of dysphagia in elder people (Age≥65) from 2004 quarter 1 through 2022 quarter 2 of FAERS by Open Vigil 2.1 database. The reported odds ratio (ROR) and the proportional reported ratio (PRR) were calculated to detect the adverse reaction signal of drug-induced dysphagia in elder people. Signal generation standard of ROR: number of reports≥3 with the lower limit of 95% confidence interval (CI) of the ROR value>1, PRR≥2 and c

Reyanning Mixture on Asymptomatic or Mild SARS-CoV-2 Infection in Children and Adolescents: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents.@*METHODS@#This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested.@*RESULTS@#A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported.@*CONCLUSION@#Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).

Association of maternal isolated thyroid peroxidase antibody positive in the first trimester with fetal growth / 北京大学学报(医学版)

OBJECTIVE@#To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth.@*METHODS@#A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del.@*RESULTS@#The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women.@*CONCLUSION@#The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.

A consensus on the management of allergy in kindergartens and primary schools / 中国学校卫生

Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Tongue and pulse features of 668 asymptomatic patients infected with the severe acute respiratory syndrome coronavirus 2 omicron variant in Shanghai.

OBJECTIVE: To characterize the tongue and pulse manifestations in asymptomatic coronavirus disease 2019 (COVID-19) cases in Shanghai. METHODS: We conducted a clinical study of 668 patients with asymptomatic infections in which we analyzed the tongue and pulse features in the Shanghai New International Expo Center mobile cabin hospital. The medical records of the patients, including tongue color, tongue coating, and pulse manifestations, were reviewed by healthcare workers. RESULTS: In total, 668 COVID-19 cases were included in the study. Patient age ranged from 5 to 96 years, with a median of 44.0 (IQR 33.0-53.0) years. Among the patients, 6.14% had comorbidities. The most common comorbid condition was diabetes (1.65%), followed by hypertension (0.89%), coronary heart disease (0.89%), thrombotic diseases (0.89%), congestive heart failure (0.60%), and stroke (0.45%). Pink-red (75.4%) was the most common tongue color, followed by red (23.4%) and pale red (1.2%). Tongue coating color and thickness were classified as white fur (9.28%), thin and yellow fur (48.65%), white greasy fur (8.98%), yellow greasy fur (24.70%), and less coating (8.39%). In addition, a large number of patients ( 300, 44.91%) presented superficial and rapid pulses, and 250 patients (37.4%) exhibited a slippery pulse. CONCLUSION: Our preliminary results showed that wind, heat, and dampness were the main etiologies of the severe acute respiratory syndrome coronavirus 2 Omicron (B.1.1.529) variant infection in traditional Chinese medicine. Furthermore, the main symptoms of the disease may be wind-heat invading the lung syndrome or damp-heat with the exuberance of virulence syndrome, which is of most significance in COVID-19 treatment.

Analysis of clinical characteristics and prognosis of 4 264 patients with asymptomatic and mild novel coronavirus infections in Shanghai / 中华危重病急救医学

Objective:To analyze the clinical characteristics and prognosis of patients infected with novel coronavirus Omicron variant in Shanghai, as to provide a reference for epidemic prevention, clinical diagnosis, and treatment.Methods:Altogether 4 264 novel coronavirus Omicron variant-infected patients with positive results of nucleic acid admitted to Shanghai New International Expo Center N3 Mobile Cabin Hospital from April 2 to May 7, 2022, were included. The demographic and baseline clinical characteristics, treatment strategy, prognosis, and different factors affecting the length of hospital stay were analyzed.Results:A total of 4 264 novel coronavirus variant Omicron-infected cases were collected, including 3 111 cases (73.0%) asymptomatic infections and 1 153 cases (27.0%) mild infections. The overall median age was 45 (33, 55) years old with a range from 2 years old to 81 years old. The male to female ratio was 1.37∶1. Altogether 3 305 cases (77.5%) had been vaccinated, of which 3 166 cases completed more than 2 doses. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical manifestations of these infected patients. During the course of the disease, patients with asymptomatic infection were mainly treated with traditional Chinese medicine (TCM, 55.1%) and clinical observation (36.8%), and those with mild infection were mainly treated with TCM (42.2%) or integrated Chinese and Western medicine (30.4%). All patients were cured and discharged. The overall median length of hospital stay and the negative conversion time of nucleic acid were 9 (6, 10) days and 8 (5, 9) days, respectively. Compared with the asymptomatic infected patients, the hospitalization duration and the nucleic acid negative conversion time of the mildly infected patients were slightly longer [days: 10 (8, 11) vs. 9 (5, 10); 8 (6, 10) vs. 7 (4, 9), both P < 0.001]. Multiple linear regression analysis showed that the increasing age and mild infection were associated with longer hospitalization duration, and the treatment of TCM or integrated Chinese and Western medicine was associated with shortened length of hospital stay (all P < 0.05). Conclusions:The current novel coronavirus Omicron variant epidemic in Shanghai mainly caused asymptomatic and mild infections. The young and middle-aged population had a relatively high infection rate. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical symptoms. Elderly and confirmed patients had prolonged hospitalization duration, while for patients receiving TCM treatment, the hospitalization duration was shortened.

A survey on iodine nutrition status of children aged 8 - 10 and pregnant women in Chongqing in 2018 / 中华地方病学杂志

Objective:To learn about the iodine nutrition status of children aged 8 - 10 and pregnant women in Chongqing.Methods:From March to November 2018, according to the requirements of the "Technical Plan for Iodine Deficiency Disorders Monitoring in Chongqing in 2018", in all 39 counties (districts) of the city, each county (district) was divided into 5 sampling areas according to the orientation of east, west, south, north and middle. One township/street was selected from each area, one primary school was selected from each township/street, and 40 non-boarding students aged 8 - 10 (age balanced, half male and half female) were selected from each primary school. At the same time, 20 pregnant women (balanced in early, middle and late pregnancy) were selected from each township/street. Household edible salt and random urine samples from children and pregnant women were collected to detect the contents of salt iodine and urinary iodine. Children from 13 counties (districts) were selected for thyroid examination, and the goiter rate of children was calculated.Results:Totally 7 973 and 3 927 household edible salt samples from children and pregnant women were tested, respectively. The median salt iodine was 26.20 mg/kg, the coverage rates of iodized salt were 99.07% (7 899/7 973) and 99.57% (3 910/3 927), the consumption rates of qualified iodized salt were 93.72% (7 472/7 973) and 95.03% (3 732/3 927), respectively. Totally 7 973 and 3 927 urine samples from children and pregnant women were tested, respectively. The medians urinary iodine were 228.60 and 186.30 μg/L, respectively. Among the 39 monitored counties (districts), there were no county (district) with iodine deficiency in children, and 4 counties (districts) had iodine deficiency in pregnant women. A total of 2 656 children were examined, and the goiter rate was 1.73% (46/2 656).Conclusions:In 2018, children aged 8 - 10 in Chongqing are generally at the appropriate level of iodine, and the goiter rate conforms to the national standard (< 5%). Pregnant women are generally at the appropriate level of iodine, however, pregnant women in some counties (districts) are at risk of iodine deficiency.

Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates.

Liquid-liquid phase separation promotes the formation of membraneless condensates that mediate diverse cellular functions, including autophagy of misfolded proteins. However, how phase separation participates in autophagy of dysfunctional mitochondria (mitophagy) remains obscure. We previously discovered that nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) translocates from the nucleus to mitochondria to mediate celastrol-induced mitophagy through interaction with p62/SQSTM1. Here, we show that the ubiquitinated mitochondrial Nur77 forms membraneless condensates capable of sequestrating damaged mitochondria by interacting with the UBA domain of p62/SQSTM1. However, tethering clustered mitochondria to the autophagy machinery requires an additional interaction mediated by the N-terminal intrinsically disordered region (IDR) of Nur77 and the N-terminal PB1 domain of p62/SQSTM1, which confers Nur77-p62/SQSTM1 condensates with the magnitude and liquidity. Our results demonstrate how composite multivalent interaction between Nur77 and p62/SQSTM1 coordinates to sequester damaged mitochondria and to connect targeted cargo mitochondria for autophagy, providing mechanistic insight into mitophagy.

Assessment of Malaria Microscopy Competency at Primary Health Institutions in the Chongqing Municipality.

Background: In April 2019, Chongqing passed the national malaria elimination assessment. However, around 30 imported malaria cases are still being reported every year, and Anopheles sinensis was widely distributed in Chongqing, meaning the risk of malaria resurgence still exists. Early diagnosis and treatment for malaria cases are effective measures to prevent malaria resurgence. The primary health institutions are the first station where potential malaria cases may seek treatment. The competency with which primary health institutions diagnose malaria will directly affect the timeliness of malaria diagnosis. Nowadays, most primary health institutions in Chongqing use microscopy to confirm malaria cases. This study assessed the microscopy competence of primary health institutions, studied and analyzed the results, and provided a scientific basis for malaria prevention and control after malaria elimination in Chongqing. Methods: According to the stratified sampling principle, four plasmodium microscopy technicians (156 in total) were selected from each of the 39 districts/counties of Chongqing to test the plasmodium microscopy competence. Descriptive statistical analysis, correlation analysis, spatial self-correlation analysis, and ROC curve analysis were carried out on the test results. Result: The average of the technicians' test scores was 4.33 ± 0.47 (min: 3, mid: 4.5, max: 5); The spatial clustering of the scores was significant (MoranI = 0.338, Z = 3.618, P < 0.01). The test scores were positively correlated with the "level of work institutions" (R = 0.21, P < 0.01) but were negatively correlated with "age" (R = -0.31, P < 0.01). The highest Sensitivity of the technicians' microscopy was in qualitative diagnosis (98.92%, CI: 98.00-99.69%). The Delong's test showed that the diagnostic efficiency of the technicians' microscopy to P. falciparum was the best (P < 0.01), however to P. ovale was the worst (P < 0.01). Conclusion: The microscopy technicians in primary health institutions in Chongqing have good microscopy competency in qualitative diagnosis, but there were deficiencies in the identification of plasmodium species. Township level health institutions in Central China have weaker microscopy than those in other areas.

Characteristics of progestin-insensitive early stage endometrial cancer and atypical hyperplasia patients receiving second-line fertility-sparing treatment / 부인종양

Objective@#This study investigated the characteristics of progestin-insensitive endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients receiving fertility-sparing treatments and assessed the therapeutic effects of second-line fertility-preserving treatments. @*Methods@#Three hundred and thirty-eight patients with EEC (n=75) or AEH (n=263) receiving fertility-preserving treatment were retrospectively analyzed. ‘Progestin-insensitive’ was defined as meeting one of the following criteria: 1) presented with progressed disease at any time during conservative treatment, 2) remained with stable disease after 7 months of treatment, and/or 3) did not achieve complete response (CR) after 10 months of treatment. Clinical characteristics and treatment results of progestin-insensitive patients receiving second-line treatment and those of progestin-sensitive patients were compared. @*Results@#Eight-two patients (59 AEH and 23 EEC) were defined as progestin-insensitive and 256 as progestin-sensitive. In multivariate analysis, body mass index ≥28.0 kg/m2 (odds ratio [OR]=1.898) and lesion size >2 cm (OR=2.077) were independent predictors of progestin-insensitive status. Compared to AEH patients, progestin-insensitive EEC patients had poorer second-line treatment responses (28-week cumulative CR rate after changing second-line treatment, 56.3% vs. 85.4%, p=0.011). No statistical difference was found in CR rate among different second-line treatments. @*Conclusion@#Obesity and larger lesion size were independent risk factors associated with progestin-insensitive status. In progestin-insensitive patients receiving second-line treatment, EEC patients had lower CR rate comparing with AEH patients. Further study with larger sample size is needed to evaluate efficacy of different second-line treatments for progestin insensitive patients.

Monitoring report of Keshan disease in Chongqing City in 2019 / 中华地方病学杂志

Objective:To master the current status and trend of Keshan disease in Chongqing City, and to provide scientific basis for prevention and treatment of Keshan disease in the future.Methods:In 2019, case search was carried out in 9 Keshan disease areas (counties) in Wanzhou District, Fuling District, Changshou District, Liangping District, Dianjiang County, Fengdu County, Zhong County, and Shizhu County of Chongqing City; five Keshan disease areas (counties) including Wanzhou District, Fuling District, Kaizhou District, Dianjiang County, Kaizhou District and Zhong County were selected as the monitoring sites to carry out key monitoring. Questionnaire survey, clinical examination, and electrocardiogram (ECG) were carried out on monitored subjects. The suspected cases of Keshan disease were examined by cardiac ultrasonography or posterior anterior chest X-ray.Results:A total of 25 728 cases were searched in 471 medical institutions, among which 240 suspected cases of Keshan disease were found, and 2 cases of chronic Keshan disease were confirmed. A total of 4 043 permanent residents were monitored in 5 key monitoring sites, and 813 abnormal ECG were detected, with an abnormal rate of 20.11%. Cardiac ultrasonography was performed in 40 cases, of which 19 (47.50%) cases had decreased cardiac function, 16 cases (40.00%) had thickened ventricular septal, and 11 cases (27.50%) had enlarged heart. In 56 cases of chest X-ray examination, mild, moderate and severe enlargement of heart were 9 (16.07%), 5 (8.93%) and 3 (5.36%), respectively. No case of various types of Keshan disease had been found in cardiac ultrasonography and X-ray examations.Conclusions:Chongqing City is in a stable and low incidence of Keshan disease, but some cases of chronic Keshan disease have been detected. We should continue to carry out the disease monitoring in the future.

Significance and mechanism of Tet1 against Mycobacterium marinum infection in mice / 中华微生物学和免疫学杂志

Objective:To investigate the significance and mechanism of ten-eleven translocation (Tet1) against Mycobacterium marinum ( Mm) infection in mice. Methods:SPF wild-type C57BL/6 and Tet1-knockout (Tet1KO) mice were injected intravenously with Mm. All mice were monitored and the abscesses formed in tail were observed and quantified. Pathological changes in mouse tail tissues were observed using hematoxylin and eosin (HE) staining and transmission electron microscopy and the differences between the two groups were analyzed. Immunohistochemistry staining was used to detect the expression and distribution of TNF-α and TGF-β in mouse tail tissues. Moreover, mouse tail tissues were cultured on 7H10 plates for bacterial counting. The expression of NF-κBp65 and TGF-β was detected by Western blot. Results:Obvious lesions including abscesses and ulcers were formed in the Mm-infected C57BL/6, but only scattered small abscesses were observed in Mm-infected Tet1KO mice. During Mm infection, the bacterial load was gradually increased in C57BL/6 mice, but decreased in Tet1KO mice. Histopathological examination showed that obvious inflammatory cell infiltration and typical granulomatous lesions were found in Mm-infected C57BL/6 mice, while no significant inflammatory cell infiltration was detected in Mm-infected Tet1KO mice. Immunohistochemistry staining demonstrated that the expression of TNF-α and TGF-β was lower in Mm-infected Tet1KO mice than in Mm-infected C57BL/6 mice. Moreover, the expression of phosphorylated NF-κBp65 and TGF-β was significantly reduced in Mm-infected Tet1KO mice as compared with that in Mm-infected C57BL/6 mice. Conclusions:Deletion of Tet1 could alleviate the inflammatory damage mediated by Mm and enhance the host immune response to bacteria.

A facile and universal method to achieve liposomal remote loading of non-ionizable drugs with outstanding safety profiles and therapeutic effect

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.

Development and validation of chest CT-based imaging biomarkers for early stage COVID-19 screening

Coronavirus Disease 2019 (COVID-19) is currently a global pandemic, and the early screening of COVID-19 is one of the key factors for COVID-19 control and treatment. Here, we developed and validated chest CT-based imaging biomarkers for COVID-19 patient screening. We identified the vasculature-like signals from CT images and found that, compared to healthy and community acquired pneumonia (CAP) patients, the COVID-19 patients revealed significantly higher abundance of these signals. Furthermore, unsupervised feature learning leads to the discovery of clinical-relevant imaging biomarkers from the vasculature-like signals for accurate and sensitive COVID-19 screening that has been double-blindly validated in an independent hospital (sensitivity: 0.941, specificity: 0.904, AUC: 0.952). Our findings could open a new avenue to assist screening of COVID-19 patients.

Role of long noncoding RNAs as competitive endogenous RNA in cerebral ischemia / 国际脑血管病杂志

Ischemic stroke is a common clinical cerebrovascular disease with the characteristics of high incidence rate, high mortality rate, and high disability rate. Recent studies have shown that noncoding RNAs (ncRNAs) are involved in the pathogenesis of ischemic stroke. By competitively binding miRNAs, it regulates neuronal apoptosis, inflammatory response, angiogenesis and blood-brain barrier damage in the process of ischemic brain injury. This article reviews the role of long noncoding RNAs (lncRNAs) as competitive endogenous RNAs in the pathophysiology of ischemic stroke.