Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs / 中国结合医学杂志

OBJECTIVE@#To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs.@*METHODS@#Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively.@*RESULTS@#JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05).@*CONCLUSION@#JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.

Role of Eukaryotic Translation Elongation Factor 1 Family Members in the Tumorigenesis and Progression of Lung Adenocarcinoma / 中国医学科学院学报

Objective To investigate the role and mechanism of eukaryotic translation elongation factor 1(EEF1) family members (EEF1D,EEF1A1,and EEF1A2) in lung adenocarcinoma (LUAD) based on public databases.Methods We examined EEF1 member expression levels in human LUAD samples via The Cancer Genome Atlas in the UCSC Xena browser and the Clinical Proteomic Tumor Analysis Consortium.We analyzed the mRNA and protein levels of EEF1D,EEF1A1,and EEF1A2 and their correlations with pathological variables via the Mann-Whitney U test.The Kaplan-Meier curves were established to assess the prognostic values of EEF1D,EEF1A1,and EEF1A2.The single-sample gene set enrichment analysis algorithm was employed to explore the relationship between the expression levels of EEF1 members and tumor immune cell infiltration.Spearman and Pearson correlation analyses were performed to examine the relationship between the expression levels of EEF1 members and those of the genes in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.The immunohistochemical assay was employed to determine the expression levels of EEF1D,EEF1A1,and EEF1A2 in the LUAD tissue (n=75) and paracancer tissue (n=75) samples.Results The mRNA and protein levels of EEF1D,EEF1A1,and EEF1A2 showed significant differences between tumor and paracancer tissues (all P<0.001).The patients with high protein levels of EEF1A1 showed bad prognosis in terms of overall survival (P=0.039),and those with high protein levels of EEF1A2 showed good prognosis in terms of overall survival (P=0.012).The influence of the mRNA level of EEF1D on prognosis was associated with pathological characteristics.The expression levels of EEF1 members were significantly associated with the infiltration of various immune cells and the expression of key molecules in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.Conclusion EEF1D,EEF1A1,and EEF1A2 are associated with the progression of LUAD,serving as the candidate prognostic markers for LUAD.

Paratesticular liposarcoma: the clinicopathological features of nineteen cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and differential diagnoses of paratesticular liposarcoma. Methods: The cases were collected from 2012-2020, from the archives of the Department of Pathology, Peking University Third Hospital, with diagnosis confirmed by histology, immunostaining and FISH tests. Results: Totally 19 patients were enrolled (including 11 in-hospital patients and 8 consultant cases). The patients aged 37-84 years (mean 57 years). The preoperative clinical diagnoses were spermatic cord/inguinal masses (nine patients), scrotal masses (seven patients), and inguinal hernia (three patients). Six lesions recurred after local resection, including one case extending from pelvic liposarcoma. Histologically, there were 10 cases of well-differentiated liposarcoma (WDLPS) and nine cases of dedifferentiated liposarcoma (DDLPS). WDLPSs mostly showed the combined features of lipoma-like, inflammatory and sclerosing subtypes (six patients); the other four WDLPSs had pure lipoma-like subtype features. DDLPSs were low-grade (three patients) or high-grade (six patients), with the morphology resembling myxofibrosarcoma, inflammatory myofibroblastoma, spindle cell sarcoma, pleomorphic undifferentiated sarcoma and pleomorphic liposarcoma. Intense inflammatory cells infiltration was commonly observed in five WDLPSs and two DDLPSs. Ossification was observed in three tumors. Immunohistochemically, the tumors were positive for MDM2 (8/10) and CDK4 (10/10), which were expressed in lipo-differentiating cells, spindle cells in WDLPS, and in dediffferentiated components. S-100 was only expressed by lipocytes (10/10). CD34 expression was positive and diffuse in the stromal cells of WDLPSs and focal or diffuse in dedifferentiated areas (10/10). FISH tests with an MDM2 gene probe were positive (12/12). Conclusions: Paratesticular liposarcoma may be overlooked by both clinicians and pathologists. WDLPS and DDLPS predominate, showing various histologic divergences. The presence of amplification of the 12q14-q15 region (containing the MDM2 and CDK4 genes) is helpful for making the correct diagnosis.

Serum Retinol-Binding Protein Levels Are Associated with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Real-World Study

Background@#The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM. @*Methods@#This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed. @*Results@#After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients. @*Conclusion@#Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.

Discontinuation of nucleoside/nucleoside analogues therapy in compensated patients with hepatitis B cirrhosis after HBsAg negative conversion / 中华临床感染病杂志

Objective:To evaluate the safety of discontinuing nucleoside/nucleoside analogue (NAs) therapy in patients with compensated hepatitis B cirrhosis after HBsAg negative conversion.Methods:A total of 3 783 patients with hepatitis B cirrhosis in compensated stage were treated with NAs at Taizhou Hospital, Taizhou Municipal Hospital and Taizhou Enze Hospital from January 2008 to December 2020. The clinical data and laboratory tests results of 85 patients with HBsAg negative conversion were retrospectively analyzed, including 36 cases discontinued the drug, and 49 continued to use drug. Chi-square test and rank-sum test were used for data analysis.Results:During the 24 and 48 months of follow-up, the ALT levels were within the normal range in both groups. There were no significant differences in positive rates of anti-HBs and HBeAg ( χ2=0.75, 0.39 and 0.90, P=0.78 0.84 and 0.34; χ2=0.40, 0.00 and 0.00, P=0.84, 1.00 and 1.00) between two groups. After 48 months of follow-up, 2 cases of primary liver cancer occurred in the discontinuation group and no primary liver cancer occurred in the continuation group ( χ2=0.89, P=0.34). Throughout the follow-up, HBsAg remained negative and HBV DNA load was below the lower limit of detection in both groups. Conclusions:Discontinuation of NAs can be considered after the HBsAg negative conversion in patients with compensated hepatitis B cirrhosis.

Application of Sarcosaprophagous Insects to Estimate the Postmortem Interval in 11 Cases / 法医学杂志

Objective To test the feasibility and accuracy of with sarcosaprophagous insects postmortem interval （PMI） estimation with sarcosaprophagous insects and provide references for estimation practice. Methods Eleven cases confirmed by the detection results, with complete entomological evidence were selected. The insect species, estimation results and true results involved in the cases were statistically analyzed and compared. Results Thirteen species of insects were found at the criminal scene, including Chrysomya megacephala （Fabricius）, Chrysomya rufifacies （Macquart）, Chrysomya nigripes （Aubertin）, Lucilia sericata （Meigen）, Hydrotaea spinigera Stein, Muscina stabulans （Fallén）, Sarcophagid （species were not identified）, Megaselia scalaris （Loew）, Hermetia illucens （Linnaeus）, Saprinus splendens （Paykull）, Creophilus maxillosus （Linnaeus）, Dermestes maculatus （De Geer） and Necrobia ruficollis （Fabricius）. The PMI of all eleven cases was within the range of estimated PMI. The estimated results of 72.73% cases were on the same day of the true results. Conclusion Sarcosaprophagous insects can estimate the PMI simply and conveniently. In cases where the PMI is within the time range of one generation of flies or beetles, the estimation results are relatively accurate. However, the estimation is less accurate when the PMI is beyond the time range.

Development of Dermestes Maculatus at a Constant Temperature and Its Larval Instar Determination / 法医学杂志

Objective To establish the basic data for estimating minimum postmortem interval （PMImin） of heavily decayed and skeletonized remains by studying the development of Dermestes maculatus DeGeer （Coleoptera: Dermestidae）. Methods The developmental stages of Dermestes maculatus were observed at four constant temperatures of 20 ℃, 24 ℃, 28 ℃ and 32 ℃, and the changes in body length were also examined as the biological indicator to estimate larval day-age and instar. Results The total developmental time from egg to adult at 20 ℃, 24 ℃, 28 ℃ and 32 ℃ were （126.7±10.6） d, （69.4±8.2） d, （50.4±8.4） d and （49.6±6.5） d, respectively. The body length increased gradually, but changed irregularly as a whole. Conclusion The study provides basic data on the development and growth of Dermestes maculatus, especially on its developmental duration as a significant value for estimating PMImin of heavily decayed and skeletonized remains. Nevertheless, the change of body length is not found to be the best biological indicator for instar determination.

Research Progress on Developmental Biology of Sarcosaprophagous Insects / 法医学杂志

Forensic entomology provides a feasible way to estimate postmortem interval (PMI), of which the growth and development of sarcosaprophagous insects is the most widely used indicator in forensic practice. Over the years, forensic entomologists have carried out a large number of studies on the development biology of sarcosaprophagous insects. This paper illustrates the main factors that affect the development of sarcosaprophagous insects, including temperature, humidity, light, food types and poisons. The development indicators of sarcosaprophagous insects were reviewed from the perspectives of morphology, differential gene expression and biochemical characteristics. It is emphasized that future research of development biology on sarcosaprophagous insects should fully absorb and integrate the methods of artificial intelligence and omics, and the research object also needs further expansion in order to establish a more objective and more accurate PMI estimation method.

Identification of Common Sarcosaprophagous Flies in the Yangtze River Delta by COⅠ Gene / 法医学杂志

OBJECTIVES@#To identify the common sarcosaprophagous flies in the Yangtze River Delta based on mitochondrial cytochrome c oxidase subunit Ⅰ(COⅠ) gene sequence and verify the reliability of this method.@*METHODS@#Seven common genetically stable sarcosaprophagous flies in three families and six genera were collected from large domestic pig carcasses placed in the field and cultured in the laboratory for many generations. The whole genome DNA was extracted and the COⅠ gene fragment was amplified. The forward and reverse sequencing was followed by splicing. The base composition of the amplified fragment and the rate of interspecific evolutionary divergence were analyzed by software such as Mega 7.0.26. The phylogenetic tree of COⅠ gene sequence of common necrophagous flies in the Yangtze River Delta was established by neighbor joining (NJ) method and unweighted pair-group method with arithmetic means (UPGMA) method.@*RESULTS@#The average base composition of different flies was A(30.14%), T(38.23%), C(15.98%), G(15.65%). The rate of interspecific evolutionary divergence ranged from 2.2% to 15.3%, the lowest rate was between Chrysomya megacephala and Chrysomya pinguis, the highest rate was between Muscina stabulans and Boettcherisca peregrina.@*CONCLUSIONS@#COⅠ gene can be used to identify the common necrophagous flies in the Yangtze River Delta.

Prevalence of chronic diseases among bus drivers in Hefei， Anhui / 上海预防医学

ObjectiveTo analyze the effect of working conditions on the occurrence and development of chronic diseases in bus drivers in Hefei. MethodsA total of 380 bus drivers were selected by convenient sampling method. Their basic information， working intensity， working environment， working habits， living habits and physical health were investigated. ResultsThe three most common occupational-related diseases were： 1） anxiety and depression caused by work environment such as noise and traffic jam （70.79%， 269/380）； 2） dry eyes， eye fatigue， blurred vision and so on （65.53%， 249/380）； 3） cervical and lumbar pain （63.16%， 240/380）. Gastrointestinal dysfunction （irritable bowel syndrome related symptoms） occurred in 42.37% （161/380） of the drivers and 45.53% （173/380） had suffered from hemorrhoids or anal fissure. Drivers with long-term suffocation were more likely to suffer from urinary tract infection （χ 2=22.330， P<0.001）. The rate of subjective eye discomfort was higher in the drivers with long working hours （χ 2=11.682， P<0.01）， and the rate of leg swelling was higher in the drivers with frequent driving without rest （χ 2=16.642， P<0.05）. There was a significant difference in the rate of anxiety and depression between the divers with different sleep duration （χ 2=17.379，P<0.001）. Results of multiple logistic regression analysis showed that the incidence of anxiety and depression was higher in drivers with longer working hours. In comparison with the group of over 6 working hours， the rate increased to 4.080 times in the group of over 8 working hours， 2.583 times in the group of over 10 working hours， and 2.484 times in the group of over 12 working hours， respectively. Occasional and frequent non-stop working drivers were 4.302 and 4.828 times， respectively， more likely to be anxious or depressed. Logistic regression analysis also showed that the incidence of gastrointestinal dysfunction （irritable bowel syndrome related symptoms） in drivers with anxiety and depression was 3.792 times higher than that in drivers without anxiety and depression （OR=3.792， 95% CI 2.384 to 6.029， P<0.001）. ConclusionSome working environment， excessive working intensity， poor living and working habits， and mental problems are closely related to the occurrence and development of chronic diseases in bus drivers.

Prevalence of chronic diseases among bus drivers in Hefei， Anhui / 上海预防医学

ObjectiveTo analyze the effect of working conditions on the occurrence and development of chronic diseases in bus drivers in Hefei. MethodsA total of 380 bus drivers were selected by convenient sampling method. Their basic information， working intensity， working environment， working habits， living habits and physical health were investigated. ResultsThe three most common occupational-related diseases were： 1） anxiety and depression caused by work environment such as noise and traffic jam （70.79%， 269/380）； 2） dry eyes， eye fatigue， blurred vision and so on （65.53%， 249/380）； 3） cervical and lumbar pain （63.16%， 240/380）. Gastrointestinal dysfunction （irritable bowel syndrome related symptoms） occurred in 42.37% （161/380） of the drivers and 45.53% （173/380） had suffered from hemorrhoids or anal fissure. Drivers with long-term suffocation were more likely to suffer from urinary tract infection （χ 2=22.330， P<0.001）. The rate of subjective eye discomfort was higher in the drivers with long working hours （χ 2=11.682， P<0.01）， and the rate of leg swelling was higher in the drivers with frequent driving without rest （χ 2=16.642， P<0.05）. There was a significant difference in the rate of anxiety and depression between the divers with different sleep duration （χ 2=17.379，P<0.001）. Results of multiple logistic regression analysis showed that the incidence of anxiety and depression was higher in drivers with longer working hours. In comparison with the group of over 6 working hours， the rate increased to 4.080 times in the group of over 8 working hours， 2.583 times in the group of over 10 working hours， and 2.484 times in the group of over 12 working hours， respectively. Occasional and frequent non-stop working drivers were 4.302 and 4.828 times， respectively， more likely to be anxious or depressed. Logistic regression analysis also showed that the incidence of gastrointestinal dysfunction （irritable bowel syndrome related symptoms） in drivers with anxiety and depression was 3.792 times higher than that in drivers without anxiety and depression （OR=3.792， 95% CI 2.384 to 6.029， P<0.001）. ConclusionSome working environment， excessive working intensity， poor living and working habits， and mental problems are closely related to the occurrence and development of chronic diseases in bus drivers.

Comparison of femoral tunnel and early curative effect analysis between arthroscopic three approach and traditional anteromedial portal for reconstruction of anterior cruciate ligament / 中国骨伤

OBJECTIVE@#To study the three-approach and traditional anterior medial technique to establish the femoral tunnel of position, length, and coronal angle and the early efficacy of anterior cruciate ligament reconstruction.@*METHODS@#Through retrospective research, from December 2018 to June 2019, a total of 36 patients diagnosed with simple anterior cruciate ligament tear and undergoing surgery were collected. All patients had a clear history of knee sprains and were divided into two groups. A group of 16 patients, including 11 males and 5 females, with an average age of (30.13±6.54) years and an injury time of 7 to 60 (30.19±15.78) days, three-approach technique was used to drill the femoral tunnel to reconstruct the anterior cruciate ligament. Another group of 20patients, including 15 males and 5 females, with an average age of (30.80±8.60) years, and an injury time of 7 to 60 (27.35±15.50) days, the traditional anterior medial approach was used to drill the femoral tunnel to reconstruct anterior cruciate ligament. CT 3D reconstruction technique was used to evaluate the femoral tunnel and the knee joint function was evaluated by Lysholm score of the knee joint.@*RESULTS@#All patients achieved primary healing after the surgical incision. No femoral tunnel fracture, vascular and nerve damage, difficulty in graft passage during the operation, and venous thrombosis occurred. All 36 patients were followed up on an outpatient basis, with a follow up period of 9 to 15 (12.00±2.83) months. Three-dimensional CT reconstruction was used to evaluate the femoral tunnel of the patients. The position of the femoral tunnel was described using the quartile method as the three-approach group:the lower (27.83±1.97) % of the femoral condyle and the posterior (25.57±3.20) %;the traditional approach group:the lower (28.38±3.21) % of the femoral condyle and the posterior (26.23±3.20) %. Bone tunnel length, three-approach group:(35.20±5.52) mm in total length, (23.20±2.07) mm in thick bone tunnel;traditional approach group:(34.60±4.26) mm in total length, (22.56±2.50) mm in thick bone tunnel. Coronal plane angle, three-approach group:(47.93±5.98) °;traditional approach group:(41.78±6.62) °. Knee joint Lysholm score, three-approach group:48.67±4.18 before surgery;97.00±2.48 at last follow up;traditional approach group:49.75±5.33 before surgery, 97.30±2.68 at last follow up, there were significant differences before and after surgery, no significant statistical difference between two groups.@*CONCLUSION@#The positions of the femoral tunnel drilled by the two methods were within the range of the anatomic stop of the anterior cruciate ligament, and there was no statistical difference. Compared with the traditional anterior medial approach, the coronal plane angle of the femoral tunnel drilled by the three-approach approach is relatively large, and there were no statistical differences in the length of the tunnel, the early postoperative effect of the two surgical methods, and the operation time. But the three approach has a wider and clearer vision. In addition, the knee flexion angle required for drilling the femoral tunnel during surgery is significantly smaller than that of traditional approach technology, which reduces the difficulty of surgery.

Untargeted Metabolomic Profiling of Liver and Serum in Mouse during Normal Aging / 中国医学科学院学报

Objective To obtain the metabolome profiles in liver and serum of mice during normal aging. Methods The liver and serum samples of ten 2-month-old mice and ten 18-month-old C57BL/6J mice under physiological conditions were collected.Metabolites were identified and quantified by liquid chromatography-tandem mass spectrometry.The overall assessment,differential screening,and functional analysis were performed with the filtered high-quality data. Results In the negative-ion mode and positive-ion mode,242 and 399 metabolites were identified in the liver and 265 and 230 in serum,respectively.The difference of metabolome between young and old mice was moderate.The upregulated metabolites identified in aging liver were related to the metabolism of riboflavin,glucose,and arachidonic acid,while the downregulated ones were associated with the metabolism of pyrimidine,purine,glycerophospholipid,glutathione,and nicotinamide.Altered metabolites in serum during aging were involved in a variety of nucleic acid metabolism-related pathways,such as pyrimidine metabolism,purine metabolism,one carbon pool by folate,and amino sugar and nucleotide sugar metabolism. Conclusions The metabolome profiles of mouse liver and serum both revealed dysregulated nucleic acid metabolism pathways during normal aging.This study provides metabolome data for further research on aging-associated mechanism and may support the discovery of intervention methods for aging.

Proteome and Acetylome Profiling of Livers in C57BL/6J Male Mice during Normal Aging / 中国医学科学院学报

Objective To obtain the proteome and acetylome profiles of livers in mice during normal aging.Methods We applied tandem mass tag labeling and liquid chromatography tandem mass spectrometry and achieved proteome and acetylome data in C57BL/6J male mice aged 2 and 18 months under physiological conditions.Results A total of 4712 proteins were quantified by proteome profiling,and 4818 acetylated sites in 1367 proteins by acetylome profiling.The proteome and acetylome revealed moderate differences in the livers of young and old mice.There were 195 differentially expressed proteins in the proteome and 113 differentially expressed acetylated sites corresponding to 76 proteins in the acetylome.Functional enrichment analysis for the proteome showed that aging-associated upregulated proteins were mainly involved in fatty acid metabolism,epoxygenase P450 pathway,drug catabolic process,organic hydroxy compound metabolic process,and arachidonic acid metabolic process,while the downregulated proteins were related to regulation of gene silencing,nucleosome assembly,protein heterotetramerization,response to interferon,protein-DNA complex assembly and other processes.For the acetylome,the proteins with aging-associated upregulated acetylated sites mainly participated in cofactor metabolism,small molecule catabolic process,ribose phosphate metabolic process,ribonucleotide metabolic process,and purine-containing compound metabolic process,while the proteins with downregulated acetylated sites were associated with sulfur compound metabolic process,response to unfolded protein,and amino acid metabolic process.Conclusion We profiled the proteome and acetylome of livers in mice during normal aging and generated datasets for further research on aging.

Risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants / 中国当代儿科杂志

OBJECTIVE@#To explore the risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants.@*METHODS@#A retrospective analysis was performed for 455 very preterm infants who were admitted to the neonatal intensive care unit from January 2017 to December 2019. They were divided into an intubation group (@*RESULTS@#The intubation rate was 17.4% (79/455). Compared with the intubation group, the non-intubation group had significantly higher gestational age, birth weight, and rates of caesarean birth, delayed cord clamping (DCC), resuscitation quality improvement, regular use of antenatal glucocorticoids in mothers and premature rupture of membranes > 18 hours (@*CONCLUSIONS@#Very preterm infants with younger gestational age, birth weight < 750 g, maternal diabetes mellitus, placenta previa or placenta previa status may have a higher risk for endotracheal intubation after birth. The regular use of antenatal glucocorticoids and DCC can reduce the risk of intubation during resuscitation in very preterm infants.

Prevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing / 亚洲男科学杂志(英文版)

46,XY disorders of sex development (DSD) is characterized by incomplete masculinization genitalia, with gonadal dysplasia and with/without the presence of Müllerian structures. At least 30 genes related to 46,XY DSD have been found. However, the clinical phenotypes of patients with different gene mutations overlap, and accurate diagnosis relies on gene sequencing technology. Therefore, this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted next-generation sequencing (NGS) technology. Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital (Beijing, China). A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD. The incidence of these rare variants was approximately 69.0% (60/87). Twenty-five novel variants and 29 reported variants were identified. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance. The overall diagnostic rate was about 42.5% based on the pathogenic and likely pathogenic variants. Androgen receptor (AR), steroid 5-alpha-reductase 2 (SRD5A2) and nuclear receptor subfamily 5 Group A member 1 (NR5A1) gene variants were identified in 21, 13 and 13 patients, respectively. The incidence of these three gene variants was about 78.3% (47/60) in patients with rare variants. It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR, SRD5A2, and NR5A1 genes were the most common pathogenic genes in our cohort.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China / 生物医学与环境科学（英文）

Objective@#Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.@*Methods@#A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( @*Results@#Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.@*Conclusion@#Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Novel tumor metastasis suppressorgene LASS2/TMSG1 S248A mutant promotes invasion of prostate cancer cells through increasing ATP6V0C expression / 北京大学学报(医学版)

OBJECTIVE@#LASS2/TMSG1 gene is a novel tumor metastasis suppressor gene cloned from human prostate cancer cell line PC-3M in 1999 by Department of Pathology,Peking University of Basic Medical Sciences. It was found out that protein encoded by LASS2/TMSG1 could interact with the c subunit of vacuolar-ATPase (ATP6V0C). In this study, we explored the effect of LASS2/TMSG1 and its mutants on proliferation, migration and invasion of human prostate cancer cells and its molecular mechanism.@*METHODS@#We constructed four LASS2/TMSG1 mutants and stably transfected the variants to human prostate cancer cell line PC-3M-1E8 cell with high metastatic potential. The stable transfectants were identified by qPCR and Western blot through analyzing the expression of LASS2/TMSG1 and ATP6V0C, the cell biology functions of LASS2/TMSG1 and its four mutants were studied using growth curve,MTT assay, soft agar colony formation assay, wound migration assay, Matrigel invasion study and flow cytometry. Furthermore, immunofluorescence was used to analysis the interaction of LASS2/ TMSG1 mutants and ATP6V0C.@*RESULTS@#LASS2/TMSG1 mRNA and protein in LASS2/TMSG1 group and Mut1-Mut4 groups were higher than that in Vector group; Western blot showed that ATP6V0C protein in LASS2/TMSG1 wild group was lower than that in Vector group, but ATP6V0C protein in LASS2/TMSG1 S248A group was obviously higher than that in Vector group. MTT test and growth curve assay showed growth ability in LASS2/TMSG1 S248A group was increasing compared with other groups from day 5. Soft Agar colony formation experiment showed anchor independent growth ability in LASS2/TMSG1 S248A group was higher than those in the other groups (P<0.05), Cell migrations (from 35.3%±3.2% to 70.3%±3%) in LASS2/TMSG1 S248A group was increasing compared with LASS2/TMSG1 wild group (P<0.01), and more cells passed through Matrigel in LASS2/TMSG1 S248A group compared with LASS2/TMSG1 wild group (from 50±3.2 to 203±6.5, P<0.01), the apoptosis rate in LASS2/TMSG1 S248A group was obviously higher than that in LASS2/TMSG1 wild group (from 7% to 15.1%, P<0.05), and the G0/G1 ratio in LASS2/TMSG1 S248A group was obviously higher than that in LASS2/TMSG1 wild group (from 51.0% to 85.4%). Furthermore, double immunofluorescent staining observed the colocalization between ATP6V0C and LASS2/TMSG1 protein and its mutations, the expression of ATP6V0C in LASS2/TMSG1 S248A group increased significantly compared with the other groups.@*CONCLUSION@#LASS2/TMSG1 S248A promotes proliferation, migration and invasion of prostate cancer cells through increasing ATP6V0C expression, suggesting that aa248-250 is an important function site for LASS2/TMSG1 in invasion suppression of prostate cancer cells.

Analysis on traditional Chinese medicine prescriptions treating cancerous fever based on grey screening method combined with multivariate analysis method and discovery of new prescriptions / 中国中药杂志

Cancerous fever is one of the common symptoms of advanced malignant tumors,which seriously affects the quality of life and survival of patients. At present,the clinical research on the treatment of cancerous fever by traditional Chinese medicine is limited,and there is a lack of research on the medication rules from multiple dimensions of disease-symptom-syndrome. The treatment of cancerous fever has not made substantial progress. In this study,we collected the literature on treatment of cancerous fever in Chinese medicine,and concluded that common syndrome types include Yin deficiency type,Qi deficiency type,Yang deficiency type,blood stasis type,damp-heat accumulation type,toxic heat flourishing type and liver meridian stagnated heat type. Two hundreds and fifty-seven prescriptions for Chinese medicine and 249 flavors for single medicine were extracted. The analysis of the drug composition of the drug found that the cancerous fever treatment was mainly based on heat-clearing drugs and deficiency-nourishing drugs. Apriori association analysis of the drug found that the second and third related drugs were mainly Rehmanniae Radix,Moutan Cortex,Artemisiae Annuae Herba,Trionycis Carapax and Anemarrhenae Rhizoma. The top five gray correlation degrees were Psoraleae Fructus,Bupleuri Radix,Hordei Fructus Germinatus,Scutellariae Radix and Massa Medicata Fermentata. And seven new prescriptions were evolved. The results showed that the treatment of cancerous fever can be started from the disease-symptom-syndrome,nourishing Yin and clearing heat is an important method for " disease differentiation and treatment". The combination of Bupleuri Radix and Scutellariae Radix is the embodiment of " symptom differentiation and treatment". The new prescriptions conform to the idea of " syndrome differentiation and treatment" of traditional Chinese medicine can provide reference for clinical medication. The grey screening method combined with multivariate analysis method was used to analyze the prescription rules of Chinese medicine in the treatment of cancer fever,which followed the black box structure of traditional Chinese medicine,made the potential rule of prescriptions explicit,broadened its thinking of Chinese medicine treatment,and made up for the deficiency of traditional analysis methods.