Melatonin Attenuates Mitochondrial Damage in Aristolochic AcidInduced Acute Kidney Injury

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

Application of pathological feature clustering in oral pathology teaching / 中华口腔医学杂志

To propose a new student-guided teaching method, in which students carried out the clustering of different diseases with the same pathological characteristics, and differentiated diagnosis of these diseases. This method was named pathological feature clustering (PFC). Seventy-seven undergraduates of School of Stomatology, Wuhan University were enrolled. Stratified random sampling method was adopted to divide the students into 4 groups with 18-20 students in each group. Each group of students selected a disease from the following four topics as the theme and summarize the histological characteristics of the disease: ①oral mucosal disease;②odontogenic tumors and tumor-like lesions, oral and maxillofacial cysts; ③salivary gland diseases;④epithelial-derived tumors and tumor-like lesions (referred to as topics 1, 2, 3, and 4, respectively). When discussing a specific type of disease, the group which select the topic was the summary group (SG), and the other groups were the non-summary group (NSG). After summarizing, students shared the summary results through PPTs, and teachers made comments and supplements. The teaching effect was evaluated by comparing the results of the pre-class test and the final examination. Students' acceptance of PFC teaching method was evaluated through a questionnaire, which included 8 objective questions and 1 subjective question. Likert-scale was used to design the questionnaire, with 1 to 5 points for each question. Students rated each question according to their own situation. Differences among groups were compared by Mann-Whitney U nonparametric test. The pre-class test results showed that the scores of students in SG group in subjects 1, 2, 3 [(5.6±0.8), 5.0(1.0) and (2.9±1.0) points for subjects 1, 2 and 3, respectively] were higher than those in NSG group [(5.1±1.0), 4.0(2.5) and 1.5(2.5) points] (U=402.50, P=0.047; U=392.00, P=0.026; U=295.00, P=0.003). The final examination results showed that there was no significant difference between the scores of the SG group and the NSG group in subjects 1, 2, 3 and 4 (P>0.05). These results showed that the differences between SG and NSG groups were reduced after the summarizing and share between groups, further demonstrating the effectiveness of the PFC teaching method. The results of questionnaire showed that 81.8%(63/77) students were completely satisfied with PFC teaching method, 13.0%(10/77) students were satisfied and 5.2%(4/77) students were basically satisfied. According to the feedback of Likert scale objective evaluation questionnaire, the mean score of each question ranged from 4.19 to 4.77, indicating that students believed that PFC teaching method had a positive impact on the learning of oral pathology. The PFC teaching method proposed in this study could improve the ability of pathological differential diagnosis of undergraduates.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Artificial intelligence recognition of bone marrow cells can be applied to diagnosis of minimal residual disease in acute leukemia / 中华检验医学杂志

Objective:To explore the diagnostic value and problems of artificial intelligence (AI) bone marrow cell recognition technology in the detection of minimal residual disease (MRD) of leukemia.Methods:A total of 65 cases with minimal residual disease of leukemia confirmed by flow cytometry from the Hematology Medical Center of Xinqiao Hospital affiliated to the Army Medical University (AMMU) from November 1 to December 31, 2020 were collected. The bone marrow Wright′s staining smears were obtained, and all bone marrow smears were scanned and classified automatically without artificial intervention by the analysis system based on Artificial Intelligence platform (morphogo). AI-MRD was defined to positive when the proportion of primary cells was more than 3%. According to the number of AI automatic recognition cells, the cases were divided into 18 cases of less than 500 (L500), 35 cases of 500 to 1900 (between 500 and 1900, B1900), and 12 cases of more than 1900 (M1900), no overlap or omission between groups. Kappa consistency test was performed on the results of artificial intelligence test and the results of flow cytometry for minimal residual disease of leukemia (MFC-MRD) in each group. The receiver operating characteristic curve (ROC) of the artificial intelligence test results of each group of patients was drawn based on the MFC-MRD results, and the sensitivity, specificity and accuracy of the area under the curve (AUC) value and AI results were calculated.Results:After grouping according to the number of cells automatically recognized by AI, the detection results of L500 group were MFC-MRD+/AI-MRD+7 cases, MFC-MRD+/AI-MFC-2 cases, MFC-MRD-/AI-MRD+6 cases, MFC-MRD-/AI-MRD-3 cases; In B1900 group, MFC-MRD+/AI-MRD+13 cases, MFC-MRD+/AI-MFC-6 cases, MFC-MRD-/AI-MRD+6 cases, MFC-MRD-/AI-MRD-10 cases; The results of M1900 group were MFC-MRD+/AI-MRD+5 cases, MFC-MRD+/AI-MFC-0 cases, MFC-MRD-/AI-MRD+1 case, MFC-MRD-/AI-MRD-6 cases. Taking MFC-MRD as the determination standard, the sensitivity of AI-MRD detection in L500 group, B1900 group and M1900 group was 53.8%, 68.4% and 83.3%, the specificity was 60%, 62.5% and 100%, the accuracy was 55.6%, 65.7% and 91.7%, and the AUC value were 0.568 P=0.654, 0.678 P=0.069,1.000 P=0.000. Conclusions:This study preliminarily explored the diagnostic value and problems of AI bone marrow cell recognition in the detection of minimal residual disease of leukemia. It was confirmed that when 3% of the proportion of blasts in AI cell classification is set>3% as the positive threshold of AI-MRD, the consistency between AI and MFC-MRD detection increases with the increase of the number of cells recognized by AI.

Clinical efficacy of free deep inferior epigastric artery perforator flap in repair of large wounds in upper limb / 中华显微外科杂志

Objective:To summarise the clinical efficacy of free deep inferior epigastric artery perforator flap (DIEPF) in repairing large wounds in upper limb.Methods:From June 2016 to March 2022, free DIEPF repair surgery were performed for 9 cases with large defects in elbow, forearm and wrist in the Department of Hand Surgery, Xuzhou Renci Hospital. The patients were 3 males and 6 females at 36-65(average 50) years old. The sizes of defect ranged from 6.0 cm×7.0 cm to 25.0 cm×33.0 cm. Seven defects combined with radius-ulnar fracture, 4 with wrist fracture, 4 with metacarpal fracture and 1 with humerus fracture. All defects had various degrees of injuries of tendon, blood vessel and nerve. A total of 10 flaps were harvested, and the size of flaps were 7.0 cm×8.0 cm-12.0 cm×35.0 cm. Vessels in 7 flaps of 6 patients were anastomosed with unilateral vascular pedicles and 3 with bilateral vascular pedicles. End-to-end arterial anastomosis was performed on 1 flap, and the other 9 flaps of 8 patients had end-to-side arterial anastomoses. End-to-end vein anastomoses were performed on all flaps. Umbilical reconstruction was performed at the abdominal donor site for 3 patients, and all donor site wounds were closed in stage I surgery. Scheduled outpatient and WeChat follow-up were made after surgery.Results:Nine flaps in 8 patients survived successfully. Partial skin necrosis occurred in 1 flap and repaired by skin grafting. Follow-up lasted for 6 to 60 months(12 months in average). At the last follow-up, the colour of the flaps was found being similar to the surrounding skin with mildly bloated and soft in texture. Sensation of the flaps recovered to S 2 in 5 patients, and not detected in 4 cases. Conclusion:The free DIEPF has a relatively constant perforator and the flap can be used for repairing a large area of defect. The donor site wound can be closed in Ⅰ stage surgery. Free DIEPF is suitable for repair of large upper limb wounds.

Cost-effectiveness analysis of an artificial intelligence-assisted diagnosis and treatment system for gastrointestinal endoscopy / 中华消化内镜杂志

Objective:To analyze the cost-effectiveness of a relatively mature artificial intelligence (AI)-assisted diagnosis and treatment system (ENDOANGEL) for gastrointestinal endoscopy in China, and to provide objective and effective data support for hospital acquisition decision.Methods:The number of gastrointestinal endoscopy procedures at the Endoscopy Center of Renmin Hospital of Wuhan University from January 2017 to December 2019 were collected to predict the procedures of gastrointestinal endoscopy during the service life (10 years) of ENDOANGEL. The net present value, payback period and average rate of return were used to analyze the cost-effectiveness of ENDOANGEL.Results:The net present value of an ENDOANGEL in the expected service life (10 years) was 6 724 100 yuan, the payback period was 1.10 years, and the average rate of return reached 147.84%.Conclusion:ENDOANGEL shows significant economic benefits, and it is reasonable for hospitals to acquire mature AI-assisted diagnosis and treatment system for gastrointestinal endoscopy.

Prenatal phenotypic analysis and genetic counseling for 22q11.21 microdeletion and microduplication syndrome / 中华围产医学杂志

Objective:To analyze the prenatal clinical phenotypes and pregnancy outcomes of fetuses with 22q11.21 microdeletion and microduplication syndrome to provide a basis for clinical genetic counseling.Methods:This retrospective study involved the cases diagnosed with 22q11.21 microdeletion or microduplication by chromosomal microarray analysis (CMA) due to abnormal ultrasound findings, advanced maternal age, or high-risk pregnancies indicated by serum screening in the Prenatal Diagnosis Center of the First Affiliated Hospital of Air Force Medical University from January 2015 to January 2022. Clinical phenotypes and pregnancy outcomes of the fetuses were analyzed and described.Results:Among 9 141 cases referred for CMA during the study period, 77 cases (0.8%) were diagnosed as 22q11.21 microdeletion or microduplication, including 62 (80.5%) with 22q11.21 microdeletion and 15 (19.5%) with microduplication. In the 22q11.21 microdeletion cases, 58 had typical deletion, and four had atypical deletions, but all fetuses carried TBX1 gene that was clearly associated with congenital heart disease. The 15 fetuses with 22q11.21 microduplication including 14 in the typical region and one in the atypical region. Forty-eight (77.4%) out of the 62 fetuses with 22q11.21 microdeletion were complicated by congenital heart defects, including 28 with conotruncal defects. Five of the 15 fetuses with 22q11.21 microduplication were complicated by congenital heart defects. The cases were followed up on telephone at three to six months after the expected date of delivery. Among the 62 cases with 22q11.21 microdeletion, 52 terminated pregnancies, five were lost to follow-up, and five were delivered (one died after one month of premature delivery, one was born with anal advancement and growth retardation, and three were followed up without obvious abnormality). Among the 15 cases with 22q11.21 microduplication, four terminated pregnancies, two were lost to follow-up, and nine gave birth (eight were followed up without obvious abnormality, one grew slowly). Conclusions:The application of CMA in the prenatal diagnosis of 22q11.21 microdeletion and microduplication fetuses, and the comprehensive analysis of clinical manifestations and pregnancy outcome combined with ultrasonic diagnosis are of great significance in guiding the treatment and rehabilitation after birth of an affected child. Genetic counseling for cases with 22q11.21 microdeletion and microduplication syndrome should be cautious and consider ultrasound findings.

Reference ranges and influencing factors of thyroid function in preterm infants at 14 d after birth / 中华围产医学杂志

Objective:To investigate the reference ranges for thyroid function and its influencing factors in preterm infants at 14 d after birth.Methods:This retrospective study involved 514 preterm infants who met the inclusion criteria in Affiliated Hospital of Inner Mongolia Medical University from January 1, 2019 to December 31, 2021. They were divided into three group according to their gestational age [early premature group (26-31 +6 weeks, n=153), middle premature group (32-33 +6 weeks, n=129) and late premature group (34-36 +6 weeks, n=232)] or birth weight (BW) [<1 500 g group ( n=129), 1 500-2 000 g group ( n=120) and ≥2 000 g group ( n=265)]. Venous blood samples were collected from the infants at 14 d after birth and their thyroid function was determined by chemiluminescence immunoassay. The reference values of free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were calculated based on the values of 95% confidence intervals ( CI) and expressed as percentiles in the range from P2.5 to P97.5. Mann-Whitney U test or Kruskal-Wallis H test was used to compare those thyroid hormone levels between groups. Spearman correlation analysis was used to study the correlation of gestational age or birth weight with FT 3, FT 4 and TSH levels. The factors influencing the levels of thyroid hormones were analyzed by multiple linear regression. Results:The reference ranges for FT 3, FT 4 and TSH were 1.53-3.72 pg/ml, 0.81-1.91 ng/dl and 1.32-7.80 μIU/ml in the early premature infants, 1.74-4.16 pg/ml, 0.90-2.82 ng/dl and 0.63-7.64 μIU/ml in middle prematures and 2.07-4.88 pg/ml, 1.09-2.27 ng/dl and 1.14-7.06 μIU/ml in late prematures. The reference ranges for the above three indexes were 1.53-4.06 pg/ml, 0.81-1.83 ng/dl and 1.14-7.84 μIU/ml in premature infants with BW<1 500 g, 1.67-3.98 pg/ml, 0.88-2.97 ng/dl and 0.94-7.64 μIU/ml in those whose BW between 1 500 g and 2 000 g and 1.91-4.75 pg/ml, 1.09-2.31 ng/dl and 1.14-6.32 μIU/ml in those whose BW≥2 000 g. Multiple linear regression showed that the level of FT 3 was positively correlated with gestational age ( β=0.119, P<0.05) and birth weight ( β=1.950×10 －4, P<0.05); that of FT 4 was positively correlated with gestational age only ( β=0.031, P<0.05); and TSH level was negatively correlated with birth weight ( β=－4.250×10 －4, P<0.05). Conclusions:Gestational age and birth weight are the factors influencing thyroid function in preterm infants at 14 d after birth. Evaluation of thyroid function with FT 4 and TSH should based on the references ranges of different gestational age and birth weight .

Glucagon-like peptide-1 receptor agonists and glycemic management in non-critical hospitalized patients / 中华内分泌代谢杂志

In recent years, with the continuous development of glucagon-like peptide-1 receptor agonists(GLP-1RA), its role in the management of blood glucose in hospitalized patients has been explored. GLP-1RA can not only control blood glucose in non-critically ill hospitalized patients, but also inhibit appetite, delay gastric emptying, protect nerves, anti-inflammation, reduce systolic blood pressure and blood lipids. At the same time, many studies have found that it can also improve cardiovascular and renal outcomes and reduce the risk of hospitalization complications. Therefore, this paper analyzes the role of GLP-1RA in glycemic management by reviewing domestic and international studies, consensus and guidelines related to inpatient blood glucose management, and helps to better manage blood glucose of patients in non-critical care setting.

Establishment of a hyperuricemia rat model by stimulation of high temperature-humidity environment / 中华内分泌代谢杂志

Objective:To establish a hyperuricemia rat model through the high temperature-humidity treatment, and monitor its vital signs and biochemical indicator characteristics, as well as observe the changes of renal histomorphology and ultrastructure.Methods:Male SD rats were randomly divided into control(CON) group, potassium oxonate(PO) group and high temperature-humidity(HTH) group, 6 rats each. The experiment lasted for 6 consecutive weeks. Rats from PO group was given 250 mg/kg PO by gavage every day. The rats from HTH group were treated with a special thermostatic incubator for one hour each day after gavaging 250 mg/kg PO. Serum uric acid, creatinine and other indicators were detected every 2 weeks. After 6 weeks, the kidney tissues were collected. The morphological changes and urate crystal deposition of kidney tissues were observed by hematoxylin-eosin staining, Masson′s trichrome staining and gomori staining, while the ultramicrostructural changes of kidney were observed by transmission electron microscope.Results:Two weeks after the experiment, the average serum uric acid values of PO group and HTH group increased significantly, HTH group was higher than PO and CON groups[(133.9±17.8), (107.6±12.4), and (85.7±4.1) μmol/L, P=0.001]. And after 6 weeks, the HTH group was still higher than the other two groups[(115.1±27.8), (82.7±13.9), and (72.9±17.8) μmol/L, P=0.008). The average serum creatinine in HTH group was slightly higher than that in PO group and CON group at 6 weeks[(46.2±4.7), (38.1±6.0), and (28.3±6.3) μmol/L, P=0.001]. Light microscope showed partial renal tubular dilatation in PO group, but renal tubular epithelial cells swelling and inflammatory cells infiltration were more significant in HTH group. The ultrastructural changes such as glomerular podocyte swelling were found in HTH group by transmission electron microscope. Conclusion:In this study, we had successfully established a hyperuricemia rat model by simulating the high temperature-humidity environment combined with potassium oxyzinate after 2 weeks of experiment. After 6 weeks of modeling, it was found that the high temperature-humidity induced rat models possessed a relatively higher and stabler serum uric acid level than that of the traditional chemical medicine induced rats. The method can be applied to the research of pathogenesis and pharmacotherapy of hyperuricemia caused by high temperature-humidity environment.

Autosomal dominant osteopetrosis type Ⅱ: 2 cases report and literature review / 中华内分泌代谢杂志

Osteosclerosis is a rare hereditary bone metabolic disease, characterized by increased bone mass and density caused by bone resorption disorders, and any abnormal mutation involving osteoclast maturation or function will lead to the occurrence of osteopetrosis. Clinically, the prevalence of autosomal dominant osteopetrosis type Ⅱ(ADO-Ⅱ) is higher than that of other types of osteopetrosis, which involves multiple systems such as endocrine, bone, blood, nerve, ear-nose-throat, and oral cavity. Disease progression is insidious and easily overlooked, and there is no standard treatment. This article summarizes the clinical characteristics, examination data, diagnosis and treatment process of the two patients, analyzes multi-system symptoms, pathogenesis and treatment principles of the disease to improve the management of patients with ADO-Ⅱ.

Clinical and genetic analysis of five pedigree with maturity-onset diabetes of the young type 2 / 中华内分泌代谢杂志

Objective:To explore the clinical and molecular genetic characteristics of patients with maturity-onset diabetes of the young type 2(MODY2).Methods:Clinical data and laboratory results were collected from five MODY2 patients and their family members diagnosed in the Department of Endocrinology, Genetics, and Metabolism of Xi ′an Children′s Hospital in the recent two years. Whole exome sequencing was carried out on every proband to identify potential variants, then the suspected variants were verified with Sanger sequencing in family numbers.Results:Among the 5 probands, except for proband 4 who presented with polydipsia and polyuria, hyperglycemia in the rest of the children was accidentally identified. Urine routine, urinary protein, and blood lipid of the five probands were all normal, and HbA 1C was between 5.96% and 8.15%. Moreover, an important discovery in this study was that proband 5 had insulin resistance(IRS), which was different from previous studies. It was confirmed by genetic analysis that a glucokinase(GCK) gene variant existed in every MODY2 pedigree. There were four GCK variants in this study, including c. 146C>T(p.T49I), c. 1237T>G(p.Y413D), c. 683C>T(p.T228M) and c. 952G>T(p.G318W), among which the C. 1237T>G(P.y413d) and C. 952G>T(P.G318W) had not been reported till now. All probands received lifestyle intervention, and the blood glucose control was relatively stable. Conclusion:There is MODY2 patient complicated with IRS. MODY2 patients can be controlled well by lifestyle interventions. In addition, we discovered two novel variants of GCK, which extend the mutation spectrum of this gene.

Development of professional grief scale for medical postgraduate students and its reliability and validity / 中华行为医学与脑科学杂志

Objective:To develop a professional grief scale for medical postgraduate students(PGS-MPS) and test its reliability and validity.Methods:Based on the integrated model of professional grief, the initial item pool was formed after literature analysis, semi-structured interviews, group discussion, and 5 experts were invited to assess the relevance of the items and provided revision suggestion.A total of 506 valid questionnaires were collected.SPSS 25.0 and AMOS 26.0 were used to test its reliability and validity.Results:The PGS-MPS included 41 items, including the professional grief reaction subscale and disenfranchised grief subscale.The professional grief reaction subscale included emotional reaction (14 items), physiological and cognitive reaction (20 items), and the cumulative variance contribution rate of the two factors model was 52.908%.Disenfranchised grief subscale included 7 items, with a single dimension and a variance contribution rate of 51.730%.Confirmatory factor analysis indicated the model fitting well.The Cronbach’s α coefficients for the professional grief reaction subscale and disenfranchised grief subscale were 0.947 and 0.850, respectively.Conclusion:The PGS-MPS has good reliability and validity and can be used to evaluate professional grief of medical postgraduate students.

Triaging patients in the outbreak of COVID-2019 / 中国感染控制杂志

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Gut microbiota profiles in the perioperative period and long-term postoperative period in children with ventricular septal defect treated with cardiopulmonary bypass / 中华实用儿科临床杂志

Objective:To explore the characteristics of gut microbiota in the preoperative, short-term postoperative and long-term postoperative period at (15.61±4.51) months in children with ventricular septal defect (VSD) of congenital heart disease (CHD) treated with cardiopulmonary bypass (CPB).Methods:A prospective study was conducted.In Guangzhou Women and Children′s Medical Center, 13 patients with VSD who were scheduled for CPB and additional 10 age- and gender-matched healthy infants as pre-CPB control group from January 2021 to January 2022 were enrolled.Fecal samples were collected at pre- and early post-CPB.Meanwhile, 18 gender- and CHD diagnosis and operation-matched patients at (15.61±4.51) months after CPB and 8 healthy age- and gender-matched children as long-term control group after CPB were also enrolled, and fecal samples were collected.16S rRNA sequencing of fecal samples from all subjects were performed and comparing the differences in gut microbiota between two groups via comparing alpha and beta diversity, parameter test or nonparametric test, and LEfSe analysis.Results:Compared with those of pre-CPB control group, there was a significant difference in the composition of gut microbiota in the preoperative period of VSD children, with significantly increased abundances of Enterobacteriaceae and Shigella, and decreased abundance of Bifidobacterium (all P<0.05). The diversity of gut microbiota was comparable in VSD children before CPB and in the short period time after CPB (all P>0.05), except for the abundances of Clostridium and Streptococcus (all P<0.05), and there was no significant difference in the relative abundances of other highly abundant gut bacteria between the two periods (all P>0.05). Compared with that in VSD children in the short period time after CPB, the abundances of short-chain fatty acids-producing microbes were significantly higher at (15.61±4.51) months postoperatively (all P<0.05), and the gut bacteria profile was similar to that of the long-term control group after CPB (all P>0.05). Conclusions:Gut microbiota imbalance exists in VSD children before CPB.The gut microbiota profile is not influenced by CPB, which returns normal at (15.61±4.51) months postoperatively.

Electroacupuncture improves motor function of rats with osteoarthritis by alleviating joint inflammation through the Wnt-7B/β-catenin signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of electroacupuncture on osteoarthritis in rats and explore the possible mechanism.@*METHODS@#Thirty SD rats were randomly divided into osteoarthritis model group, electro-acupuncture group and control group (n=10), and in the former two groups, early osteoarthritis was induced using a modified DMM surgical modeling method. After successful modeling, the rats in the electro-acupuncture group were treated with electro-acupuncture at bilateral "Housanli" and "Anterior knee point". Behavioral tests of the rats were performed and scored using the LequesneMG scale. Subchondral bone degeneration was observed in each group, and serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP were measured using ELISA. The mRNA and protein expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7, and MMP-3 in the cartilage tissue of the knee joints were detected using RT-PCR and Western blotting.@*RESULTS@#In behavioral tests, the rats in the model and electroacupuncture groups had significantly higher LequesneMG scores after modeling than those in the control group (P < 0.05). After 20 days of treatment, LequesneMG scores were significantly lowered in rats in the electroacupuncture as compared with the model rats (P < 0.05). Imaging examination revealed obvious subchondral bone damage in both the electroacupuncture group and the model group, but the damages were significantly milder with former group. Compared with the model rats, the rats receiving electroacupuncture had significantly lower serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP (P < 0.05) with also lower expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7 and MMP-3 in the cartilage tissues at both the mRNA and protein levels (P < 0.05).@*CONCLUSION@#Electroacupuncture can alleviate joint pain and improve subchondral bone damage in rats with osteoarthritis by reducing IL-1β levels in the joint cartilage tissue and serum to alleviate joint inflammation and by reducing such cytokines as ADAMTS-7 and MMP-3 via regulating the Wnt-7B/β-catenin signaling pathway.

Qualitative and quantitative study of constituents in Lysionoti Herba based on UHPLC-Q-Exactive Orbitrap HRMS and HPLC-UV / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Orbitrap HRMS) was employed to systematically analyze the chemical constituents in Lysionoti Herba, and high perfor-mance liquid chromatography-ultraviolet(HPLC-UV) to determine the content of main compounds. A Synergi~(TM) Hydro-RP 100 Å colu-mn(2 mm×100 mm, 2.5 μm) was used for gradient elution with acetonitrile-0.1% aqueous formic acid as the mobile phase at a flow rate of 0.2 mL·min~(-1) and a column temperature of 40 ℃. MS and MS/MS were conducted with electrospray ionization(ESI) in both positive and negative modes. The chemical components in Lysionoti Herba were identified by comparison with the retention time and mass spectra of reference compounds and the relevant mass spectral data reported in MS databases and relevant literature. Furthermore, the content of five constituents(neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin) in different Lysiono-ti Herba samples was simultaneously determined by HPLC-UV at the wavelength of 330 nm. A total of 84 compounds were identified in Lysionoti Herba, including 27 flavonoids, 20 phenylethanoid glycosides, 5 amino acids, 18 organic acids, 1 alkaloid, 6 nucleosides, and 7 others. The content of neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin showed good linear relationship(r>0.999) with the peak area within certain concentration ranges, which were 3.22-102.90, 12.84-410.82, 31.63-1 012.01, 25.00-800.11, and 4.08-130.51 μg·mL~(-1), respectively. The instrument precision, method repeatability, and solution stability all met requirement, and the average recovery rate was 97.31%-100.2%, with RSD ranging from 0.95% to 2.4%. The content of the five components varied among different Lysionoti Herba samples collected from different regions of Guizhou, and the average content of forsythoside B was the highest. The established qualitative method can rapidly and efficiently identify the chemical components of Lysionoti Herba, and the developed HPLC-UV method can simultaneously determine the content of five components in a simple, ra-pid, and accurate manner, providing a scientific basis for the quality evaluation of Lysionoti Herba.

Problems and thoughts in clinical safety evaluation of traditional Chinese medicine / 中国中药杂志

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Evaluation methods of clinical efficacy of traditional Chinese medicine / 中国中药杂志

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.