Analysis of intraoperative frozen section diagnosis of 1 263 pulmonary nodules / 中国胸心血管外科临床杂志

@#Objective    To explore the key points and difficulties of intraoperative frozen section diagnosis of pulmonary diseases. Methods    The intraoperative frozen section and postoperative paraffin section results of pulmonary nodule patients in Beijing Chaoyang Hospital, Capital Medical University from January 2021 to January 2022 were collected. The main causes of misdiagnosis in frozen section diagnosis were analyzed, and the main points of diagnosis and differential diagnosis were summarized. Results    According to the inclusion criteria, a total of 1 263 frozen section diagnosis results of 1 178 patients were included in the study, including 475 males and 703 females, with an average age of 58.7 (23-86) years. In 1 263 frozen section diagnosis results, the correct diagnosis rate was 95.65%, and the misdiagnosis rate was 4.35%. There were 55 misdiagnoses, including 18 (3.44%) invasive adenocarcinoma, 17 (5.82%) adenocarcinoma in situ, 7 (35.00%) mucinous adenocarcinoma, 4 (2.09%) minimally invasive adenocarcinoma, 3 (100.00%) IgG4 related diseases, 2 (66.67%) mucinous adenocarcinoma in situ, 1 (16.67%) atypical adenomatous hyperplasia, 1 (14.29%) sclerosing pulmonary cell tumor, 1 (33.33%) bronchiolar adenoma, and 1 (100.00%) papillary adenoma. Conclusion    Intraoperative frozen section diagnosis still has its limitations. Clinicians need to make a comprehensive judgment based on imaging examination and clinical experience.

Clinical characteristics of liver function injury in patients with coronavirus disease 2019 / 中华传染病杂志

Objective:To investigate the incidence of liver injury in patients with coronavirus disease 2019 (COVID-19), and to explore its impact on the condition and prognosis of patients.Methods:The medical records of 67 patients with COVID-19 who presented with pneumonia hospitalized at Tongji Hospital, Huazhong University of Science and Technology from February 11 to March 28, 2020 were collected. The results of liver biochemistry and coagulation function test at admission were analyzed. Data were compared by chi-square test, analysis of variance or Kruskal-Wallis H test. Results:Among 67 patients, total bilirubin increased in seven (10.4%) patients, which was slightly abnormal, albumin decreased in 36(53.7%) cases, and was below 30 g/L in 15(22.4%) cases, alanine transaminase (ALT) and aspartate transaminase (AST) were elevated in 19(28.4%) and 12(17.9%) cases, respectively. A total of 22(32.8%) cases had elevated ALT and (or) AST. The incidences with elevated ALT and (or) AST in moderate and severe patients were 33.3%(10/30) and 26.9%(7/26), respectively. Five of 11 critical patients had elevated ALT and (or) AST. There was no significant difference among the three groups ( χ2=1.21, P=0.546). Abnormal alkaline phosphatase and (or) γ-glutamyl transpeptidase were observed in 11(16.4%) cases. The prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT) occurred in 10(14.9%) and 17(25.4%) patients, respectively, while most of them were slightly abnormal. Only one patient presented with prolongation of PT and APTT meeting the standard of liver failure. A total of 61.2%(41/67) and 65.7%(44/67) of cases showed increase of fibrinogen and D-dimer, respectively, and 28.4%(19/67) and 19.4%(13/67), respectively increased to an obvious extent. The albumin levels in moderate, severe and critical patients were (37.85±6.19) g/L, (32.96±4.33) g/L and (33.02±3.63) g/L, respectively, which were significantly different ( F=7.36, P=0.001). There were significant differences in PT, APTT, fibrinogen and D-dimer among the three groups ( F=3.22, 3.31, 4.06 and H=17.63, respectively, all P<0.05). Conclusions:COVID-19 only leads to mild liver injury and has only mild impact on liver function. The decrease of albumin level and the increase of fibrinogen and D-dimer may be early predicting indexes for the disease severity.

Research progress of DNA methylation in idiopathic male infertility / 中国医师杂志

Male infertility is a multifactorial disease, of which the cause of male infertility cannot be determined, which is called idiopathic male infertility, and the incidence rate is gradually rising. Because its cause is unknown, it has become a major problem in the department of reproductive endocrinology. With the in-depth study of epigenetics, the diagnosis and treatment of idiopathic male infertility also has a new direction, especially the important role of DNA methylation in spermatogenesis and embryonic development. More and more gene fragments and loci have been found by scholars, which makes it possible to achieve accurate identification and targeted treatment. This article reviews and summarizes the research progress of DNA methylation related to idiopathic male infertility in recent years, aiming to further elaborate the pathogenesis of idiopathic male infertility and provide new ideas for clinical diagnosis and treatment.

Prevalence and risk factors of metabolic syndrome among adults in Hainan Province / 中国热带医学

@#Abstract: Objective　This study aims to explore the prevalence and risk factors of metabolic syndrome (MS) among the adults in Hainan Province, and to provide scientific basis for MS prevention and control. Methods　A multi-stage cluster random sampling method was applied to select 3 690 permanent residents aged 18 years and above in Hainan Province. The survey was conducted by trained investigators using household appointments and centralized surveys. A questionnaire survey, physical measurement, and laboratory examination were conducted after the collection of blood samples. The processed samples were then tested by a quality-controlled laboratory. Finally, we analysed the prevalence of metabolic syndrome (MS) and its relationship with population characteristics and health-related behaviors. Results　The crude prevalence of MS in the population aged 18 and above in Hainan province was 19.46% and the standardized prevalence was 13.21%, with a higher rate in urban areas (22.21%) than in rural areas (18.13%). The prevalence of MS increased with age (P<0.001), and there were significant differences in MS prevalence among different marital and occupational statuses (P<0.01). Logistic regression results indicated that the age groups of 40-<50 years (OR=2.986, 95%CI:1.355-6.580), 50-<60 years (OR=3.739, 95%CI: 1.715-8.151), 60-<70 years (OR=3.890, 95%CI: 1.769-8.556), 70 years and above (OR=3.927, 95%CI: 1.758-8.771), technical, transportation and production personnel (OR=1.579, 95%CI: 1.033-2.412), retired (OR=1.788, 95%CI: 1.415-2.259), unemployed (OR=1.503, 95%CI: 1.044-2.165), smoking cessation (OR=1.582, 95%CI: 1.162-2.154), insufficient intake of fruits and vegetables (OR=1.196, 95%CI: 1.005-1.422), and insufficient physical activity (OR=1.437, 95%CI: 1.155-1.787) were all associated with the prevalence of MS. Among the investigated subjects, 30.22% of them had one abnormal component, with hyperglycemia being the highest (54.44%); 24.25% of them had two abnormal components, with "hyperglycemia + hypertension" being the highest (33.30%); and 19.46% had three or more components, with "overweight/obesity + hyperglycemia + hypertension" being the highest (24.79%). Conclusions　The prevalence of MS in Hainan Province is on the rise, and effective lifestyle intervention measures are needed to reduce the risk of MS.

Bioinformatics analysis and prokaryotic expression of Strongyloides stercoralis serine protease inhibitor 1 / 中国血吸虫病防治杂志

Objective To predict the structure and antigenic epitope of the Strongyloides stercoralis serine protease inhibitor 1 (Ss-SRPN-1) protein using bioinformatics tools, and to construct prokaryotic expression plasmids for expression of recombinant Ss-SRPN-1 protein, so as to provide the basis for unraveling the function of the Ss-SRPN-1 protein. Methods The amino acid sequence of the Ss-SRPN-1 protein was downloaded from the NCBI database, and the physicochemical properties, structure and antigenic epitopes of the Ss-SRPN-1 protein were predicted using bioinformatics tools, including ExPASy, SWISS-MODEL and Protean. Primers were designed according to the nucleotide sequences of Ss-SRPN-1, and the Ss-SRPN-1 gene was amplified, cloned and sequenced with genomic DNA extracted from the infective third-stage larvae of S. stercoralis as a template. The Ss-SRPN-1 protein sequence was cloned into the pET28a (+) expression vector and transformed into Escherichia coli BL21 (DE) cells for induction of the recombinant Ss-SRPN-1 protein expression. The recombinant Ss-SRPN-1 protein was then purified and identified using Western blotting and mass spectrometry. Results Bioinformatics analysis showed that the Ss-SRPN-1 protein, which was composed of 372 amino acids and had a molecular formula of C1948H3046N488O575S16, was a stable hydrophilic protein, and the subcellular localization of the protein was predicted to be extracellular. The Ss-SRPN-1 protein was predicted to contain 11 dominant B-cell antigenic epitopes and 20 T-cell antigenic epitopes. The Ss-SRPN-1 gene with a length of 1 119 bp was successfully amplified, and the recombinant plasmid pET28a (+)/Ss-SRPN-1 was constructed and transformed into E. coli BL21(DE) cells. The expressed recombinant Ss-SRPN-1 protein had a molecular weight of approximately 43 kDa, and was characterized as a Ss-SRPN-1 protein. Conclusions The recombinant Ss-SRPN-1 protein has been expressed successfully, and this recombinant protein may be a potential vaccine candidate against strongyloidiasis.

Comparison of emotional and behavioral problems of preschool children in only child and multiple child families / 中国学校卫生

Objective@#To explore the emotional and behavioral problems of different only child and multiple child families, and to provide a reference for developing effective parenting styles.@*Methods@#A stratified random cluster sampling method was adopted to investigate 2 647 guardians of preschool children in Tongling City from April to June, 2022. Children s emotional and behavioral problems were evaluated by using the self designed parenting questionnaire and the Children s Strengths and Difficulties Questionnaire (SDQ) parent edition.@*Results@#The abnormal total score detection rate of emotional and behavioral problems of preschool children was 15.5%, and the rate of abnormal peer interaction was the highest (19.5%). In multiple child families, the first born child (17.5%, 20.4%), compared with the second and third child (11.5%, 9.5%), was more likely to exhibit conduct and hyperactivity problems ( χ 2=8.44, 29.75, P <0.01). There were differences in parenting attitudes between only child and multiple child families( χ 2=9.38, P <0.05). The results of the Logistic regression analysis showed that more frequent parent child discussion, the persuasive education and consistent family discipline strategy were negatively related to the emotional and behavioral problems of only children and children in multiple child families ( OR =0.15, 0.49, 0.38; 0.34, 0.40, 0.42, P <0.05). However, harmonious family relationships were only negatively related to emotional and behavioral problems in only children ( OR =0.08, P <0.01), and a higher education level among mothers was negatively related to emotional and behavioral problems in children from multiple child family environments( OR=0.30, 0.45, P <0.05).@*Conclusion@#The emotional and behavioral problems are serious of preschool children in Tongling City, the psychological development of the oldest children from multiple child and only child families should be actively followed, as this would help to promote a better understanding of the development of preschool children s physical and mental health.

Establishment of Poly （I∶C）-induced Cytokine Storm Model in Mice and Intervention Effect of Artesunate and Qingfei Paidu Decoction / 中国实验方剂学杂志

ObjectiveTo observe the intervention effect of artesunate （ART） and Qingfei Paidu decoction （QFPD） on the mouse model of cytokine storm （CS） induced by viral mimic Poly （I∶C）. MethodEighty-four SPF male BALB/c mice were randomly divided into seven groups， with 12 mice in each group. Mice， except for those in the blank group （n=12）， were subjected to CS model induction by tail vein injection of Poly （I∶C） at 15 mg·kg-1， followed by drug treatments of low-dose ART （ART-l， 10 mg·kg-1）， medium-dose ART （ART-m， 20 mg·kg-1）， high-dose ART （ART-h， 40 mg·kg-1）， Qingfei Paidu Decoction （QFPD， 2.4 g·kg-1）， and dexamethasone （DXM， 10 mg·kg-1）. After 6 hours， lung tissues， bronchoalveolar lavage fluid （BALF）， spleen， lung， and peripheral blood were collected. The lung and spleen indexes were calculated and the number of inflammatory cells in BALF was detected. The pathological changes in lung tissues were observed by hematoxylin-eosin （HE） staining and the levels of tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， and IL-6 in BALF were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of immune cells in BALF and peripheral blood was detected by flow cytometry. ResultThe analysis of lung and spleen indexes showed that compared with the blank group， the model group showed increased lung and spleen indexes to varying degrees （P<0.05）. Compared with the model group， the ART groups showed reduced spleen index （P<0.05） and the ART-l group showed reduced lung index （P<0.05）. Additionally， the QFPD group showed reduced lung and spleen indexes （P<0.05）. ELISA results showed that except for TNF-α， the levels of IFN-γ， IL-1β， and IL-6 in the model group increased compared with those in the blank group （P<0.05）. Compared with the model group， the ART-l group and the QFPD group showed reduced content of TNF-α （P<0.05）， and all groups with drug intervention showed reduced content of IFN-γ， IL-1β， and IL-6 （P<0.05）. The number of inflammatory cells in BALF showed a downward trend in the model group， and the number of cells increased in the groups with drug intervention except for the DXM group （P<0.05）. Flow cytometry showed that compared with the blank group， the model group showed decreased number of CD3 in the peripheral blood （P<0.05）， increased Ly-6G and F4/80 （P<0.05）， decreased expression of CD45， CD3， and F4/80 in BALF （P<0.05）， and increased expressions of Ly-6G （P<0.05）. Compared with the model group， the ART groups and QFPD group showed increased CD45 content in peripheral blood （P<0.05）， decreased Ly-6G and F4/80 content （P<0.05）， increased CD45 and F4/80 content in BALF （P<0.05）， and decreased expression of Ly-6G （P<0.05）. ConclusionART and QFPD have a good protective effect on Poly （I∶C）-induced CS in mice， and the mechanism is related to the effective intervention in immune cell disorder.

Clinical value of comprehensive intervention based on VTE risk score for venous thrombosis in elderly type 2 diabetes inpatients / 上海预防医学

ObjectiveTo explore the effect of targeted intervention measures based on risk score of venous thromboembolism （VTE）， on the prevention of senile type 2 diabetes inpatients， as well as their influence on the occurrence of venous thromboembolism. MethodsA total of 134 elderly patients with type 2 diabetes mellitus who were hospitalized in geriatrics department of Peking university third hospital during June 1， 2018 to September 30， 2018 were selected as the research subjects. All the patients were divided into control group and observation group according to random number table method， with 67 patients in each group. Patients in the control group were treated with conventional intervention methods， and patients in the observation group were treated with targeted intervention measures based on VTE risk score. After one month of intervention， the Padua score， blood glucose level and coagulation indexes of the two groups were compared. The incidence of thrombosis during the intervention period was also recorded. ResultsThe Padua score in observation group （2.09±2.17） points was significantly lower than that （3.19±2.37） points in control group （P<0.05）. The indexes of fasting blood glucose， 2h postprandial blood glucose and HbA1c in observation group were significantly lower than those in control group （P<0.05）. The fibrinogen， D-dimer， activated partial thromboplastin time and prothrombin time in observation group were significantly lower than those in control group （P<0.05）. The incidence of DVT， PVT， lower limb swelling， pain and abnormal skin color in the observation group were 4.00%， 2.00%， 2.00%， 2.00%， and 0， respectively， and in the control group were 12.00%， 10.00%， 10.00%， 12.00%， and 8.00%， respectively. The incidence of adverse events in observation group was significantly lower than that in control group （P<0.05）. ConclusionTargeted intervention based on VTE risk score can significantly reduce the risk of VTE occurrence， improve blood clotting function and blood glucose level in elderly patients with type 2 diabetes mellitus. This nursing measure has important clinical application value.

Fibroma of tendon sheath: a clinicopathological and genetic analysis of 134 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotypes and molecular genetics of fibroma of tendon sheath (FTS). Methods: One hundred and thirty-four cases of FTS or tenosynovial fibroma diagnosed in the Department of Pathology, West China Hospital, Sichuan University, Chengdu, China from January 2008 to April 2019 were selected. The clinical and histologic features of these cases were retrospectively reviewed. Immunohistochemistry, fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR) were performed on the above cases. Results: There were a total of 134 cases of FTS, including 67 males and 67 females. The patients' median age was 38 years (ranged from 2 to 85 years). The median tumor size was 1.8 cm (ranged from 0.1 to 6.8 cm). The most common site was the upper extremity (76/134, 57%). Follow-up data was available in 28 cases and there was no detectable recurrence. Classic FTS (114 cases) were well-defined and hypocellular. A few spindle-shaped fibroblasts were scattered in the dense collagenous sclerotic stroma. Characteristically elongated slit-like spaces or thin-walled vessels were observed. Most of cellular FTSs (20 cases) were well-defined and the area with increased cellularity of the spindle cells coexisted with classic FTS. There were occasional mitotic figures, but no atypical mitotic figures. Immunohistochemistry was performed in 8 cases of classic FTS and most cases were positive for SMA (5/8). Immunohistochemistry was also performed in 13 cases of cellular FTS and showed 100% positive rate for SMA. FISH was conducted on 20 cases of cellular FTS and 32 cases of classical FTS. USP6 gene rearrangement was found in 11/20 of cellular FTS. Among 12 cases of CFTS with nodular fasciitis (NF)-like morphological feature, 7 cases showed USP6 gene rearrangement. The rearrangement proportion of USP6 gene in cellular FTS without NF-like morphological features was 4/8. By contrast, 3% (1/32) of the classic FTS showed USP6 gene rearrangement. RT-PCR was performed in those cases with detected USP6 gene rearrangement and sufficient tissue samples for RT-PCR. The MYH9-USP6 fusion gene was detected in 1 case (1/8) of the cellular FTSs, while no target fusion partner was detected in the classic FTS. Conclusions: FTS is a relatively rare benign fibroblastic or myofibroblastic tumor. Our study and recent literature find that some of the classic FTS also show USP6 gene rearrangements, suggesting that classical FTS and cellular FTS are likely to be at different stages of the same disease (spectrum). FISH for USP6 gene rearrangement may be used as an important auxiliary diagnostic tool in distinguishing FTS from other tumors.

Eleven new sesquiterpenoids from peeled stems of Syringa pinnatifolia / 中国中药杂志

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.

"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Cryptic COL1A1-PDGFB fusion in dermatofibrosarcoma protuberans: a clinicopathological and genetic analysis / 中华病理学杂志

Objective: To investigate the clinicopathological and cytogenetic features of cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans (CC-DFSP). Methods: Three cases of CC-DFSP diagnosed in West China Hospital, Sichuan University, Chengdu, China from January 2021 to September 2021 were studied. Immunohistochemistry for CD34 and other markers, fluorescence in situ hybridization (FISH) for PDGFB, COL1A1-PDGFB and COL1A1, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing were performed. Results: There were three cases of CC-DFSP, including two females and one male. The patients were 29, 44 and 32 years old, respectively. The sites were abdominal wall, caruncle and scapula. Microscopically, they were poorly circumscribed. The spindle cells of the tumors infiltrated into the whole dermis or subcutaneous tissues, typically arranging in a storiform pattern. Immunohistochemically, the neoplastic cells exhibited diffuse CD34 expression, but were negative for S-100, SMA, and Myogenin. Loss of H3K27me3 was not observed in the tumor cells. The Ki-67 index was 10%-15%. The 3 cases were all negative for PDGFB rearrangement and COL1A1-PDGFB fusion, whereas showing unbalanced rearrangement for COL1A1. Case 1 showed a COL1A1 (exon 31)-PDGFB (exon 2) fusion using NGS, which was further validated through RT-PCR and Sanger sequencing. All patients underwent extended surgical resection. Except for case 3 with recurrence 2 years after surgical resection, the other 2 cases showed no recurrence or metastasis during the follow-up. Conclusions: FISH has shown its validity for detecting PDGFB rearrangement and COL1A1-PDGFB fusion and widely applied in clinical detection. However, for cases with negative routine FISH screening that were highly suspicious for DFSPs, supplementary NGS or at least COL1A1 break-apart FISH screening could be helpful to identify cryptic COL1A1-PDGFB fusions or other variant fusions.

The expression and significance of protease activated receptor 2 in ovarian epithelial carcinoma / 中华肿瘤杂志

Objective: To investigate the expression and significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods: PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas (TCGA) database and tissue genotypic expression database (GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results: The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue (3.05±0.72 vs. 0.33±0.16, P=0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect (P<0.05). Survival analysis showed that the progression free survival time (P=0.033) and overall survival time (P=0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival (P<0.05). The progression-free survival (P=0.016) and overall survival (P=0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival (P<0.05). Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis (GSEA) showed that the Wnt/β-catenin signaling pathway (P=0.023), the MAPK signaling pathway (P=0.029) and glycolysis related pathway (P=0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions: PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/β-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis.

Integrated Metagenomics and UPLC-Q-TOF-MS/MS to Explore the Mechanism of Dexamethasone on Pneumonia in Rats / 中山大学学报(医学科学版)

ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.

Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical efficacy of mild therapeutic hypothermia (MTH) with different rewarming time on neonatal hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital, Xiamen University, from January 2018 to January 2022. These neonates were randomly divided into two groups: MTH1 group (n=50; rewarming for 10 hours at a rate of 0.25°C/h) and MTH2 group (n=51; rewarming for 25 hours at a rate of 0.10°C/h). The clinical features and the clinical efficacy were compared between the two groups. A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle (SWC) on amplitude-integrated electroencephalogram (aEEG) at 25 hours of rewarming.@*RESULTS@#There were no significant differences between the MTH1 and MTH2 groups in gestational age, 5-minute Apgar score, and proportion of neonates with moderate/severe HIE (P>0.05). Compared with the MTH2 group, the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming, a significantly shorter duration of oxygen dependence, a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming, and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5, 12, and 28 after birth (P<0.05), while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups (P>0.05). There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age (P>0.05). The binary logistic regression analysis showed that prolonged rewarming time (25 hours) was not conducive to the occurrence of normal SWC (OR=3.423, 95%CI: 1.237-9.469, P=0.018).@*CONCLUSIONS@#Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours. Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC, and therefore, it is not recommended as a routine treatment method.

Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder / 中国医学科学院学报

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

Effect of Home Blood Pressure Telemonitoring Plus Additional Support on Blood Pressure Control: A Randomized Clinical Trial / 生物医学与环境科学（英文）

OBJECTIVE@#Current clinical evidence on the effects of home blood pressure telemonitoring (HBPT) on improving blood pressure control comes entirely from developed countries. Thus, we performed this randomized controlled trial to evaluate whether HBPT plus support (patient education and clinician remote hypertension management) improves blood pressure control more than usual care (UC) in the Chinese population.@*METHODS@#This single-center, randomized controlled study was conducted in Beijing, China. Patients aged 30-75 years were eligible for enrolment if they had blood pressure [systolic (SBP) ≥ 140 mmHg and/or diastolic (DBP) ≥ 90 mmHg; or SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg with diabetes]. We recruited 190 patients randomized to either the HBPT or the UC groups for 12 weeks. The primary endpoints were blood pressure reduction and the proportion of patients achieving the target blood pressure.@*RESULTS@#Totally, 172 patients completed the study, the HBPT plus support group ( n = 84), and the UC group ( n = 88). Patients in the plus support group showed a greater reduction in mean ambulatory blood pressure than those in the UC group. The plus support group had a significantly higher proportion of patients who achieved the target blood pressure and maintained a dipper blood pressure pattern at the 12th week of follow-up. Additionally, the patients in the plus support group showed lower blood pressure variability and higher drug adherence than those in the UC group.@*CONCLUSION@#HBPT plus additional support results in greater blood pressure reduction, better blood pressure control, a higher proportion of dipper blood pressure patterns, lower blood pressure variability, and higher drug adherence than UC. The development of telemedicine may be the cornerstone of hypertension management in primary care.

Influence of double jump ropes on athletes' lower limbs / Influência do salto duplo de corda de balanço nos membros inferiores dos atletas / Influencia del doble salto de cuerda de balanceo en los miembros inferiores de los atletas

ABSTRACT Introduction: The double jump rope swing is a rope jumping technique that combines the technology of vertical jump and rope swing, requiring participants to jump twice in a row with the soles of their feet. Objective: Study the effect of double-balance jump rope training on athletes' muscular strength in the lower limbs. Methods: Through the experimental process, the dynamic and kinematic parameters generated during the process of vertical jump of the participants before and after the double balance rope jump exercise were tested; the effects of double balance rope jump on the biomechanical characteristics of the lower limbs and hip, knee and ankle joints of the participants were analyzed. Results: Compared to pre-training, subjects in the experimental group improved significantly (p = 0.05). Conclusion: After double rope jump training, the subjects obtained an increase in lower limb strength and ground reaction force at the extension stage in the vertical jump. They produced greater force in less time, suggesting that the lower limb burst strength was enhanced. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O salto duplo de corda de balanço é uma técnica de salto de corda, que combina a tecnologia de salto vertical com a de balanço de corda, sendo necessário que os participantes saltem duas vezes seguidas com a sola de seus pés. Objetivo: Estudar o efeito do treinamento de salto de corda de balanço duplo sobre a força muscular nos membros inferiores dos atletas. Métodos: Mediante o processo experimental, foram testados os parâmetros dinâmicos e cinemáticos gerados durante o processo de salto vertical dos participantes antes e depois do exercício de salto de corda de balanço duplo, foram analisados os efeitos do salto de corda de balanço duplo sobre as características biomecânicas dos membros inferiores e articulações do quadril, joelho e tornozelo dos participantes. Resultados: Em comparação ao pré-treinamento, os sujeitos do grupo experimental melhoraram significativamente (p = 0,05). Conclusão: Os sujeitos obtiveram um aumento da resistência dos membros inferiores e da força de reação no solo no estágio de extensão em salto vertical após o duplo treinamento de salto de corda. Verificou-se a produção de maior força em menor tempo, sugerindo que a força de explosão nos membros inferiores foi aprimorada. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El doble salto de cuerda es una técnica de salto de cuerda que combina la técnica de salto vertical con el balanceo de la cuerda, exigiendo a los participantes que salten dos veces seguidas con la planta de los pies. Objetivo: Estudiar el efecto del entrenamiento con cuerda de doble salto de balanceo sobre la fuerza muscular en los miembros inferiores de los atletas. Métodos: A través del proceso experimental, se comprobaron los parámetros dinámicos y cinemáticos generados durante el proceso de salto vertical de los participantes antes y después del ejercicio de salto con cuerda de balanceo doble, se analizaron los efectos del salto con cuerda de balanceo doble sobre las características biomecánicas de las extremidades inferiores y las articulaciones de la cadera, la rodilla y el tobillo de los participantes. Resultados: En comparación con el preentrenamiento, los sujetos del grupo experimental mejoraron significativamente (p = 0,05). Conclusión: Los sujetos obtuvieron un aumento de la fuerza de las extremidades inferiores y de la fuerza de reacción al suelo en la fase de extensión en el salto vertical tras el entrenamiento de salto a la cuerda doble. Se verificó la producción de mayor fuerza en menos tiempo, lo que sugiere que se mejoró la fuerza de explosión en los miembros inferiores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Speed and strength training methods in athletes / Métodos de treinamento de velocidade e força em atletas / Métodos de entrenamiento de la velocidad y de la fuerza en los atletas

ABSTRACT Introduction: In recent years, China has invested in many international athletics events, and sports development, including new training methods. Objective: Explore effective training methods for speed and strength of runners in track and field events. Methods: 20 runners from the national team were randomly selected into an experimental and control group. The 10 runners in the experimental group were trained by a combination of traditional strength training and core strength training. The control group performed traditional training. All of them were subjected to fitness indicators to perform the tests. Results: There were significant differences in the speed quality index of 60 meters, and 100 meters and the strength quality index of standing triple jump, long jump, and half squat; the experiment in the control group evidenced significant differences in the speed quality index of 30 meters, 60 meters, 100 meters, and the strength quality index of standing triple jump and standing long jump; significant differences between the experimental group and the control group were evidenced in the speed quality indexes of 60 meters, 100 meters and in the strength quality indexes of triple jump and standing half squat. Conclusion: The presented protocol can significantly improve the professional athletic ability of the national team runners, especially the indicators of strength and speed. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Nos últimos anos, a China investiu em muitos eventos internacionais de atletismo, e o desenvolvimento esportivo, incluindo novos métodos de treinamento. Objetivo: Explorar métodos eficazes de treinamento para velocidade e força dos corredores em eventos de atletismo. Métodos: 20 corredores da equipe nacional foram selecionados aleatoriamente em grupo experimental e controle. Os 10 corredores do grupo experimental foram treinados por uma combinação de treinamento de força tradicional e treinamento de força central do abdome. O grupo de controle efetuou o treinamento tradicional. Todos eles foram submetidos a indicadores de aptidão física para realizar os testes. Resultados: Houve diferenças significativas no índice de qualidade de velocidade de 60 metros, 100 metros e no índice de qualidade de força de salto triplo em pé, salto em comprimento e meio agachamento; o experimento no grupo de controle evidenciou diferenças significativas no índice de qualidade de velocidade de 30 metros, 60 metros, 100 metros e no índice de qualidade de força de salto triplo em pé e salto em comprimento em pé. Diferenças significativas entre o grupo experimental e o grupo de controle foram evidenciadas nos índices de qualidade de velocidade de 60 metros, 100 metros e nos índices de qualidade de resistência de saltos triplos e meio agachamento em pé. Conclusão: O protocolo apresentado pode melhorar significativamente o nível da capacidade atlética profissional dos corredores da equipe nacional, especialmente os indicadores de força e velocidade. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: En los últimos años, China ha invertido en muchos eventos internacionales de atletismo y en el desarrollo del deporte, incluyendo nuevos métodos de entrenamiento. Objetivo: Explorar métodos de entrenamiento eficaces para la velocidad y la fuerza de los corredores en las pruebas de atletismo. Métodos: Se seleccionaron aleatoriamente 20 corredores del equipo nacional en el grupo experimental y en el de control. Los 10 corredores del grupo experimental fueron entrenados mediante una combinación de entrenamiento de fuerza tradicional y entrenamiento de fuerza del núcleo. El grupo de control realizó un entrenamiento tradicional. Todos ellos fueron sometidos a indicadores de aptitud para realizar las pruebas. Resultados: Hubo diferencias significativas en el índice de calidad de la velocidad de 60 metros, 100 metros y en el índice de calidad de la fuerza del triple salto de pie, el salto de longitud y la media sentadilla; el experimento en el grupo de control evidenció diferencias significativas en el índice de calidad de la velocidad de 30 metros, 60 metros, 100 metros y en el índice de calidad de la fuerza del triple salto de pie y el salto de longitud de pie. Se evidenciaron diferencias significativas entre el grupo experimental y el grupo de control en los índices de calidad de velocidad de 60 metros, 100 metros y en los índices de calidad de fuerza de triple salto y media sentadilla de pie. Conclusión: El protocolo presentado puede mejorar significativamente el nivel de capacidad atlética profesional de los corredores del equipo nacional, especialmente los indicadores de fuerza y velocidad. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Analysis on the difference between the payment limitations of anti-cancer drugs and the application scope of drug indications / 中国药房

OBJECTIVE To analyze the difference between the payment limitations of anti-cancer drugs and application scope of drug instructions， so as to better implement the payment policy of medical insurance drugs. METHODS The differences between the payment limitations of anti-cancer drugs and application scope of drug instructions in the National Catalogue of Drugs for Basic Medical Insurance， Industrial Injury Insurance and Maternity Insurance （2022） were compared and analyzed； the evidence-based basis of the difference was discussed， and the scope of limited payment was interpreted. RESULTS Totally 118 drugs had payment limitations； limitations scope mainly included limited evidence of gene detection results， limited indications， limited second-line and above treatment， limited payment duration， limited specialist prescription， limited medical institution grade， etc. Among them， 43 drugs had differences between the payment limitations and drug instructions， and the indications of 31 drugs were greater than payment limitations； for seven drugs， the drug indications beyond the payment limitations were recommended by the guidelines. The payment limitations of 75 drugs were consistent with drug instructions. The second-line and multi-line treatment was ineffective or intolerable with first-line drugs. There was a certain relationship between locally advanced， advanced or metastatic tumor and tumor stage， but different tumors had different criteria. Systemic treatment mainly referred to systemic treatment with drug. The results of limited genetic test required that the result was positive or negative. In addition， six kinds of TCM injections were limited to the level of medical institutions； the payment of two drugs did not exceed 12 months； when lenalidomide was combined with isazomide citrate， the medical insurance only paid for one of the drugs. CONCLUSIONS The payment limitations of some anti- cancer drugs are inconsistent with the drug indications. The drug payment limitations should be expanded according to the actual situation of clinical medication and the recommendations of guidelines. At the same time， the payment limitations should be formulated accurately and in detail， thus clinical and medical insurance staff can understand it and fully protect the interests of patients.