The value of the wireless stethoscope in patients with COVID-19 infection in a makeshift hospital.

OBJECTIVE: When COVID-19 sweeps the world, traditional stethoscopes are seen as infectious agents and then the use of stethoscopes is limited especially when health providers were in their personal protective equipment. These reasons led to the ignoring of the values of stethoscopes during pandemics. This study aims to explore the value of wireless stethoscopes in patients of a makeshift hospital. MATERIAL AND METHODS: 200 consecutive hospitalized patients with confirmed SARS-CoV-2 at Lingang Makeshift Hospital in Shanghai, China, were enrolled from April 10 to May 10, 2022 (Trial Registration Number: ChiCTR2000038272,2020/9/15). They were randomly divided into two groups. In group A (n = 100), patients were examined without a stethoscope. In group B (n = 100), lung breath sounds and heart sounds were examined with a wireless stethoscope, and positive signs were recorded. The duration of cough and tachycardia symptoms, as well as emergency cases, were compared between the two groups. In addition, the pressure, anxiety, and depression of patients in the two groups were investigated using the DAS-21 questionnaire scale, to observe the psychological impact of the stethoscope-based doctor-patient communication on patients in the makeshift hospital. RESULTS: There was no significant difference in baseline characteristics between the two groups. In group B, some significant positive signs were detected by wireless stethoscopes, including pulmonary rales and tachycardia, etc. Moreover, the therapeutic measures based on these positive signs effectively alleviated the symptoms of cough and tachycardia, which showed that the duration of symptoms was significantly shorter than that of group A (cough: 2.8 ± 0.9 vs. 3.6 ± 0.9; palpitation: 1.4 ± 0.7 vs. 2.6 ± 0.7). In particular, the number of emergency cases in group B is less than that in group A (1% vs. 3%), and the severity is lower. Notably, stethoscope-based doctor-patient communication was found to be effective in alleviating psychological measures of group B patients. CONCLUSION: Wireless stethoscopes in makeshift hospitals can avoid cross-infections and detect more valuable positive signs, which can help health providers make accurate decisions and relieve patients' symptoms more quickly. Moreover, stethoscope-based doctor-patient communication can diminish the psychological impacts of the epidemic on isolated patients in makeshift hospitals. Trial registration This study was registered in the Chinese Clinical Trial (ChiCTR2000038272) at http://www.chictr.org.cn . http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml .

Research progress on mechanism of TLR4 in carcinogenesis of inflammatory bowel disease / 中国药理学通报

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC) compared with the general population. Currently the molecular mechanism of CRC occurrence in the context of IBD is not clear. The inflammation-atypical hyperplasia-cancer process has been widely accepted. Toll-like receptor 4(TLR4) is a key receptor for pathogen recognition and immune activation, and plays a crucial role in inflammatory and carcinogenic transformation of IBD. Therefore, this paper reviews the epidemiology of colitis-associated colorectal cancer (CAC) and the main mechanisms of TLR4 in the development of IBD to CAC, which will help to further understand the carcinogenesis of IBD, detect and better describe CAC at an earlier stage, and provide more effective prevention and treatment for CAC.

Study on antidepressant effects of Nrf2/HO-l of volatile oil from Chai Dang Bo drug-group on OB model rats and its mechanism / 中国药理学通报

Aim To confirm the antidepressant effect of the volatile oil part of the disassembled prescription drugs (Chai Hu, Dang Gui and Bo He, referred to as CDB) from Xiaoyao Powder and investigate its mechanism via Nrf2/H0-1 signaling pathway on OB model rats. Methods GC-MS analysis of the main components of volatile oil part of CDB was performed. The rats were randomly divided into sham operation group, model group, fluoxetine hydrochloride group (FLX, 10 mg • kg

Comprehensive assessment of mismatch repair and microsatellite instability status in molecular classification of endometrial carcinoma / 中华妇产科杂志

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.

An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat: How Does the Brain Breathe? / 神经科学通报·英文版

The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.

Clinical value of complete lateral position endoscopic combined intra-renal surgery in treatment of staghorn kidney calculi / 中国医师进修杂志

Objective:To assess the safety and feasibility of complete lateral position endoscopic combined intra-renal surgery (ECIRS) in treatment of staghorn kidney calculi.Methods:The clinical data of 105 patients with staghorn kidney calculi from March 2016 to July 2022 in the First Hospital of Shanxi Medical University were retrospectively analyzed. Among them, 55 patients were treated with lateral position percutaneous nephrolithotomy (PCNL) (PCNL group), and 50 patients were treated with complete lateral position ECIRS (ECIRS group). The operative time, removal time of double J-tube, postoperative hospital stay, postoperative hemoglobin decrease value, operative complications (using Clavien-Dindo grading criteria), additional postoperative intervention and calculi free rate were compared between two groups.Results:Both groups of patients were successfully operated. The operative time, postoperative hemoglobin decrease value and rate of additional postoperative intervention in ECIRS group were significantly lower than those in PCNL group: (98.3 ± 19.1) min vs. (103.4 ± 16.5) min, (9.34 ± 3.04) g/L vs. (12.55 ± 4.75) g/L and 8.00% (4/50) vs. 21.82% (12/55), the calculi free rate was significantly higher than that in PCNL group: 90.00% (45/50) vs. 74.55% (41/55), and there were no statistical differences ( P<0.05 or <0.01); there were no statistical differences in the removal time of double J-tube, postoperative hospital stay, incidence of Clavien-Dindo≥ grade Ⅱ operative complications between two groups ( P>0.05). Conclusion:The complete lateral position ECIRS is a safe and effective treatment for staghorn kidney calculi, and is a good complement to the ECIRS technique because of its high stone free rate in phase Ⅰ, low complication incidence and easy dissemination.

Stem cell transplantation for mevalonic aciduria: a case report and literature review / 中华实用儿科临床杂志

Clinical data of a child with mevalonic aciduria (MA) who underwent stem cell transplantation (SCT) in the Department of Rheumatology and Immunology, Children′s Hospital, Capital Institute of Pediatrics in March 2019 were retrospectively analyzed.A girl aged 2 years and 11 months old presented with recurrent fever for 2 years and 11 months and swelling of both knees for 9 months was enrolled.The child also had specific facial features and development delay.The urinary mevalonic acid and inflammatory factor levels were increased.The whole exome sequencing showed compound heterozygous mutations c. 439G>A (p.A147T) and c. 976G>A(p.G326R) in the MVK gene.After achieving a partial remission following the treatment of Tocilizumab, the patient was treated with SCT and thus yielded the complete remission.Through literature review of a total of 39 children with MA, most of cases suffer MA since the infancy.All systems can be affected by MA.Clinical manifestations of the nervous system abnormalities, recurrent fever, hepatosplenomegaly, delayed physical development, gastrointestinal symptoms, and eye involvement were helpful for the diagnosis of MA.To date, 10 cases (including one case in this study) of MA have been reported to receive SCT after achieving a partial remission of other treatment, and 7 finally achieve a complete remission.This case report provided references that SCT is an effective treatment to children with MA who fail to achieve a complete remission after conventional treatment.

Effect of Modified Gegen Qinliantang on FXR/SHP/PPARα Signaling Pathway in Type 2 Diabetic db/db Mice / 中国实验方剂学杂志

ObjectiveTo observe the effect of modified Gegen Qinliantang on the expression levels of proteins related to the farnesoid X receptor/small heterodimer partner/peroxisome proliferator-activated receptor α （FXR/SHP/PPARα） signaling pathway in the liver tissue of db/db model mice with type 2 diabetes mellitus （T2DM） and explore the underlying mechanism of action of modified Gegen Qinliantang. MethodThirty db/db mice were randomly divided into model group， metformin group （0.2 g·kg-1）， and high-， medium-， and low-dose modified Gegen Qinliantang groups （31.9， 19.1， 6.4 g·kg-1）， with 6 mice in each group. An additional six m/m mice were assigned to the blank group. Respective drugs were administered via oral gavage for 12 weeks. Mouse body weight， fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels were measured. Oil red O staining was used to observe hepatic lipid accumulation and periodic acid-schiff （PAS） staining was used to assess hepatic glycogen deposition. Ammonium ferric sulfate staining was used to observe cholesterol deposition in intestinal tissues. Western blot was employed to detect the expression of FXR， cholesterol 7α-hydroxylase （CYP7A1）， SHP， and PPARα proteins in liver tissues， and enzyme-linked immunosorbent assay （ELISA） was used to measure serum free fatty acid （FFA） levels. ResultAt the end of the treatment， compared with the blank group， the model group exhibited significant increases in mouse body weight， FBG， FFA， TC， TG， and LDL-C levels （P<0.01）， along with significant hepatic lipid droplets， reduced hepatic glycogen， noticeable cholesterol accumulation in intestinal tissues， significantly decreased expression of FXR， SHP， PPARα proteins， and significantly increased expression of CYP7A1 protein in liver tissues （P<0.01）. Compared with the model group， the metformin group and the high- and medium-dose modified Gegen Qinliantang groups demonstrated significant reductions in mouse body weight， FBG， FFA， TC， TG， LDL-C levels （P<0.05， P<0.01）， significant increases in HDL-C levels （P<0.05， P<0.01）， decreased hepatic lipid accumulation， increased hepatic glycogen， reduced intestinal cholesterol accumulation， significantly increased expression of FXR， SHP， PPARα proteins， and significantly decreased expression of CYP7A1 protein in liver tissues （P<0.01）. ConclusionModified Gegen Qinliantang may regulate the FXR/SHP/PPARα signaling pathway to suppress FFA levels and improve lipid metabolism in T2DM mice.

Effect of Modified Gegen Qinliantang on TGR5/cAMP/GLP-1 Signaling Pathway in Pancreatic Tissue of Type 2 Diabetes Mellitus db/db Mice / 中国实验方剂学杂志

ObjectiveTo discuss the effect of modified Gegen Qinliantang （MGQT） on blood glucose and lipids and Takeda G protein-coupled receptor 5 （TGR5）-related pathways in pancreatic tissue of obese type 2 diabetes mellitus （T2DM） mice. MethodA total of 10 male specific pathogen free （SPF） m/m mice （7 weeks old） and 50 male SPF （7 weeks old） were adaptively fed for one week in SPF laboratory. The m/m mice were included in the blank group. T2DM was induce d in the 50 db/db mice. The model mice were randomized into the model group， metformin group （0.2 g·kg-1）， high-dose， medium-dose， and low-dose （31.9， 19.1， 6.4 g·kg-1） MGQT groups， with 10 in each group， and the drug dose was10 mL·kg-1. The model group and the blank group received distilled water of the same volume. The administration lasted 12 weeks （once/day）. Fasting blood glucose （FBG） was detected regularly. After 12 weeks of administration， serum levels of glycated serum protein （GSP）， serum glucose （GLU）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected. Pathological changes in the pancreatic tissue were based on hematoxylin-eosin （HE） staining. Western blot was used to determine the protein expression of TGR5， protein kinase A （PKA）， phosphorylated （p）-PKA， cyclic-AMP response element binding protein （CREB）， p-CREB， proprotein convertase 1/3 （PC1/3）， and glucagon-like peptide-1 （GLP-1） in pancreatic tissues. The level of cyclic adenosine monophosphate （cAMP） in pancreatic tissue was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the blank group， the model group had pathological changes in pancreatic tissue， high levels of FBG， GSP， GLU， TC， TG， and LDL-C （P<0.01）， low level of HDL-C （P<0.05）， low protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in pancreatic tissue （P<0.01）， and low content of cAMP in the pancreas （P<0.01）. Pancreatic tissue lesion in the treatment groups were milder than that in the model group. Both the high-dose MGQT and metformin can reduce the levels of FBG， GSP， GLU， TC， TG， and LDL-C in db/db mice （P<0.05， P<0.01） and increase the level of HDL-C （P<0.01）. Except the GLP-1 protein in the medium-dose MGQT group， the protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in the high-dose and medium-dose MGQT groups and the metformin group increased compared with that in the model group （P<0.05， P<0.01）. The content of cAMP in the pancreatic tissue of the high-dose and medium-dose MGQT groups and the metformin group was raised compared with that in model group （P<0.05， P<0.01）. ConclusionMGQT can improve the glucose homeostasis in db/db mice with T2DM by regulating TGR5/cAMP/GLP-1 signaling pathway-related protein expression.

Development and validation of a score predicting mortality for older patients with mitral regurgitation / 老年心脏病学杂志（英文版）

OBJECTIVE@#To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.@*METHODS@#The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.@*RESULTS@#Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).@*CONCLUSIONS@#The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Analysis of the characteristics of SPTB gene variants among 16 children with Hereditary spherocytosis / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation.@*METHODS@#Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test.@*RESULTS@#The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.@*CONCLUSION@#Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.

Uterine POLE mutant endometrioid carcinoma combined with human papilloma virus-associated cervical adenocarcinoma: A case report and literature review / 北京大学学报(医学版)

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.

Activation of JAK/STAT in ovarian high-grade serous cancers and its prognostic significance / 北京大学学报(医学版)

OBJECTIVE@#The activation of Janus kinase (JAK) and signal transducers and activators of transcription (STAT) plays an important role in the prognosis and targeted therapy of ovarian high-grade serous carcinoma (HGSC). Utilizing simple and practicable technique, this study aimed to evaluate the activation of JAK/STAT signaling pathway in ovarian HGSC patients, and investigated the correlation between the activation of JAK/STAT signaling pathway and the prognosis of the HGSC patients.@*METHODS@#We performed immunohistochemistry of phosphorylated STAT3 (pSTAT3) and phosphorylated STAT5 (pSTAT5) on paraffin imbedded slides of 73 ovarian HGSC patients, and evaluated the expression level and range of both markers. According to the grading score of the immunostaining of pSTAT3 and pSTAT5, we divided the 73 ovarian HGSC cases into STAT3 low/high expression and STAT5 low/high expression groups, and analyzed the prognosis of the patients in different groups, in order to explore the relationship between the expression of pSTAT3 and pSTAT5 proteins and the prognosis of the HGSC patients.@*RESULTS@#Some of the ovarian HGSC cases showed high expression of pSTAT3 and pSTAT5 protein level, which was related to the poorer prognosis of the HGSC patients. There was a significant difference in the expression level of pSTAT3 and pSTAT5 between the patients with better prognosis (survival time ≥3 years) and poorer prognosis (survival time < 3 years). The patients with higher protein expression of pSTAT3, pSTAT5 or both markers might have poorer prognosis, with significant shorter progression-free survival time and overall survival time (P < 0.001).@*CONCLUSION@#Immunostaining of pSTAT3 and pSTAT5 proteins might be helpful to evaluate and predict the prognosis of the ovarian HGSC patients, and to identify the patients who might have higher chances to respond to the STAT inhibitors and anti-angiogenesis therapy.

Effects of the kynurenine pathway on the osteogenic differentiation of periodontal ligament stem cells / 中华口腔医学杂志

Objective: To explore the effect of kynurenine pathway on the osteogenic differentiation of periodontal ligament stem cells (PDLSC). Methods: Unstimulated saliva samples were collected from 19 patients with periodontitis (periodontitis group) and 19 periodontally healthy individuals (health group) in Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University from June to October of 2022. Contents of kynurenine and the metabolites in saliva samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The expressions of indoleamine 2, 3-dioxygenase (IDO) and aryl hydrocarbon receptor (AhR) were further detected by immunohistochemistry in gingival tissues. The PDLSC used in this study were isolated from extracted teeth for orthodontic treatment in Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University from July to November of 2022. Experiments were then conducted using the cells by incubating with (kynurenine group) or without kynurenine (control group) in vitro. Seven days later, alkaline phosphatase (ALP) staining and assays of ALP activity were performed. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to detect the expressions of osteogenic related genes ALP, osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), collagen type-Ⅰ (COL-Ⅰ) as well as the kynurenine pathway-associated genes AhR, cytochrome P450 family (CYP) 1A1, CYP1B1. Western blotting was used to detect the expression levels of RUNX2, osteopontin (OPN) and AhR proteins on day 10 and alizarin red staining was performed to observe the formation of mineral nodules on day 21 in control group and kynurenine group. Results: Salivary concentrations of kynurenine [8.26 (0, 19.60) nmol/L] and kynurenic acid [11.4 (3.34, 13.52) nmol/L] were significantly higher in the periodontitis group than in the health group [0.75(0, 4.25) nmol/L, 1.92(1.34, 3.88) nmol/L] (Z=-2.84, P=0.004; Z=-3.61, P<0.001). The expression levels of IDO (18.33±2.22) and AhR (44.14±13.63) in gingival tissues of periodontitis patients were significantly higher than that of the health group (12.21±2.87, 15.39±5.14) (t=3.38, P=0.015; t=3.42, P=0.027). In vitro, the ALP activity of PDLSC in the kynurenine group (291.90±2.35) decreased significantly compared with the control group (329.30±19.29) (t=3.34, P=0.029). The mRNA expression levels of ALP, OCN and RUNX2 in the kynurenine group (0.43±0.12, 0.78±0.09, 0.66±0.10) were decreased compared with the control group (1.02±0.22, 1.00±0.11, 1.00±0.01) (t=4.71, P=0.003; t=3.23, P=0.018; t=6.73, P<0.001), while the levels of AhR and CYP1A1 were increased in the kynurenine group (1.43±0.07, 1.65±0.10) compared with those in the control group (1.01±0.12, 1.01±0.14) (t=5.23, P=0.006; t=6.59, P<0.001). No significant difference was observed in COL-Ⅰ and CYP1B1 mRNA levels between groups. The protein levels of OPN, RUNX2 (0.82±0.05, 0.87±0.03) were reduced and that of AhR (1.24±0.14) was increased in the kynurenine group compared with those in the control group (1.00±0.00, 1.00±0.00, 1.00±0.00) (t=6.79, P=0.003; t=7.95, P=0.001; t=3.04, P=0.039). Conclusions: Over-activated kynurenine pathway in periodontitis patients can promote upregulation of AhR and suppress the osteogenic differentiation of PDLSC.

Predictive factors for sequelae of bronchitis obliterans in refractory Mycoplasma pneumoniae pneumonia / 中华儿科杂志

Objective: To investigate the predictive factors for bronchitis obliterans in refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods: A restrospective case summary was conducted 230 patients with RMPP admitted to the Department of No.2 Respiratory Medicine of Beijing Children's Hospital, Capital Medical University from January 2013 to June 2017 were recruited. Clinical data, laboratory results, imaging results and follow-up data were collected. Based on bronchoscopy and imaging findings 1 year after discharge, all patients were divided into two groups: one group had sequelae of bronchitis obliterans (sequelae group) and the other group had not bronchitis obliterans (control group), independent sample t-test and nonparametric test were used to compare the differences in clinical features between the two groups. Receiver operating characteristic (ROC) curve to explore the predictive value of Bronchitis Obliterans in RMPP. Results: Among 230 RMPP children, there were 115 males and 115 females, 95 cases had sequelae group, the age of disease onset was (7.1±2.8) years;135 cases had control group, the age of disease onset was (6.8±2.7) years. The duration of fever, C-reative protein (CRP) and lactate dehydrogenase (LDH) levels, the proportion of ≥2/3 lobe consolidation, pleural effusion and the proportion of airway mucus plug and mucosal necrosis were longer or higher in the sequelae group than those in the control group ((17±9) vs. (12±3) d, (193±59) vs. (98±42) mg/L,730 (660, 814) vs. 486 (452, 522) U/L, 89 cases (93.7%) vs. 73 cases (54.1%), 73 cases (76.8%) vs.59 cases (43.7%), 81 cases (85.3%) vs. 20 cases (14.8%), 67 cases (70.5%) vs. 9 cases (6.7%), t=5.76, 13.35, Z=-6.41, χ2=14.64, 25.04, 22.85, 102.78, all P<0.001). Multivariate Logistic regression analysis showed that the duration of fever ≥10 days (OR=1.200, 95%CI 1.014-1.419), CRP levels increased (OR=1.033, 95%CI 1.022-1.044) and LDH levels increased (OR=1.001, 95%CI 1.000-1.003) were the risk factors for sequelae of bronchitis obliterans in RMPP. ROC curve analysis showed that CRP 137 mg/L had a sensitivity of 82.1% and a specificity of 80.1%; LDH 471 U/L had a sensitivity of 62.7% and a specificity of 60.3% for predicting the development of bronchitis obliterans. Conclusions: The long duration of fever (≥10 d), CRP increase (≥137 mg/L) may be used to predict the occurrence of sequelae of bronchitis obliterans in RMPP. It is helpful for early recognition of risk children.

Fumarate hydratase deficient uterine leiomyoma: a clinicopathological and molecular analysis of 80 cases / 中华病理学杂志

Objective: To investigate the clinicopathologic and molecular characteristics of fumarate hydratase (FH) deficient uterine leiomyoma. Methods: Eighty cases of FH deficient uterine leiomyoma were diagnosed from April 2018 to September 2022 in Department of Pathology, Peking University Third Hospital. Sanger sequencing of FH gene exons (exon 1-10) were performed on tumor tissues and matched non-tumor tissues/peripheral blood for all cases. FH immunohistochemistry were performed in 74 cases; S-(2-succino)-cysteine (2SC) were also detected by immunohistochemistry in five cases. Results: Patients' age ranged from 18 to 54 (36.0±7.5) years, with more than 60% exhibiting clinical symptoms of multiple and large leiomyomas (the median diameter was 70 mm). More than four histologic features, including staghorn vasculature, alveolar-pattern edema, bizarre nuclei, oval nuclei arranged in chains, prominent eosinophilic nucleoli with perinucleolar haloes and eosinophilic intracytoplasmic globules were observed in 98.5% (67/68) patients. The immunohistochemical sensitivity of FH and 2SC were 97.3% and 100%, respectively. Based on the Sanger sequencing results, the cases were divided into germline variant group (31 cases), somatic variant group (29 cases) and no variant group (20 cases). Sixty-nine percent (20/29) of the patients with FH germline variation had clear family history. Conclusions: Clinical features, histological morphology, FH and 2SC immunohistochemistry and Sanger sequencing have their own significance and limitations in differential diagnosis of FH deficient uterine leiomyoma. In clinical practice, the above information should be fully integrated and studied for accurate pathologic diagnosis and selection of patients with FH germline variation.

Role of Flow Cytometry in the Diagnosis of Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance.@*METHODS@#The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups.@*RESULTS@#The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group (P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group (P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group (P <0.001), though there was no significant difference in MFI.@*CONCLUSION@#The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.

Functional characterization and enzymatic properties of flavonoid glycosyltransferase gene CtUGT49 in Carthamus tinctorius / 中国中药杂志

Carthami Flos, as a traditional blood-activating and stasis-resolving drug, possesses anti-tumor, anti-inflammatory, and immunomodulatory pharmacological activities. Flavonoid glycosides are the main bioactive components in Carthamus tinctorius. Glycosyltransferase deserves to be studied in depth as a downstream modification enzyme in the biosynthesis of active glycoside compounds. This study reported a flavonoid glycosyltransferase CtUGT49 from C. tinctorius based on the transcriptome data, followed by bioinformatic analysis and the investigation of enzymatic properties. The open reading frame(ORF) of the gene was 1 416 bp, encoding 471 amino acid residues with the molecular weight of about 52 kDa. Phylogenetic analysis showed that CtUGT49 belonged to the UGT73 family. According to in vitro enzymatic results, CtUGT49 could catalyze naringenin chalcone to the prunin and choerospondin, and catalyze phloretin to phlorizin and trilobatin, exhibiting good substrate versatility. After the recombinant protein CtUGT49 was obtained by hetero-logous expression and purification, the enzymatic properties of CtUGT49 catalyzing the formation of prunin from naringenin chalcone were investigated. The results showed that the optimal pH value for CtUGT49 catalysis was 7.0, the optimal temperature was 37 ℃, and the highest substrate conversion rate was achieved after 8 h of reaction. The results of enzymatic kinetic parameters showed that the K_m value was 209.90 μmol·L~(-1) and k_(cat) was 48.36 s~(-1) calculated with the method of Michaelis-Menten plot. The discovery of the novel glycosyltransferase CtUGT49 is important for enriching the library of glycosylation tool enzymes and provides a basis for analyzing the glycosylation process of flavonoid glycosides in C. tinctorius.