Premature ovarian insufficiency(POI) is a manifestation of ovarian aging, with a global incidence of 3.5%. If not addressed in time, POI can rapidly develop into premature ovarian failure(POF). The incidence of POI is mainly related to genetic factors, iatrogenic factors, autoimmunity, aging, infection, psychological factors, and other influences. POI not only causes menstrual disorders, amenorrhea, infertility, and dyspareunia but also tends to present with symptoms such as mood swings, insomnia, hot flashes, fatigue, as well as osteoporosis, coronary heart disease, diabetes, and other conditions, resulting in long-term psychological and physical health concerns for affected women. From traditional Chinese medicine(TCM)'s perspective, POI is primarily attributed to kidney Yin deficiency, with the main pathogenesis rooted in kidney deficiency, which affects the heart, liver, and spleen. It manifests in different syndrome types, including kidney deficiency with liver Qi stagnation, kidney deficiency with blood stasis, and spleen-kidney Yang deficiency. TCM employs a holistic view, utilizing multi-component TCM, multi-site acupuncture, and multi-target and multi-pathway interventions to treat POI. It offers unique advantages such as strong personalization, high safety, and good efficacy. In this paper, the animal and clinical research literature on the prevention and treatment of POI in the past 10 years was systematically summarized and reviewed. It is found that TCM mainly treats POI and alleviates POI-caused issues such as menstrual disorders, infertility, and emotional instability by regulating the neuroendocrine system(hypothalamic-pituitary-ovarian axis, HPOA) and related signaling pathways, improving ovarian function and antioxidant capacity, enhancing immune function, maintaining mitochondrial energy metabolism, inhibiting ferroptosis, and controlling endoplasmic reticulum stress.
Humans ; Primary Ovarian Insufficiency/physiopathology* ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Medicine, Chinese Traditional

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

OBJECTIVE: To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax, chidamide, and azacitidine in the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 15 elderly AML patients aged≥60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax, chidamide and azacitidine, and the efficacy, treatment-related adverse events, overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: After one course of treatment, 11 out of 15 patients achieved complete response (CR), 3 patients achieved CR with incomplete hematologic recovery (CRi), and 1 patient died due to prior infection before efficacy evaluation, and the overall response rate (ORR) was 93.3% (14/15). The median follow-up time was 131 (19-275) days, with median OS and EFS both remaining unreached. Next-generation sequencing (NGS) analysis showed that among the 15 patients, 13 were detected with gene mutations, and there were 7 genes with mutation frequencies of more than 10%, including ASXL1 (4 cases), RUNX1 (4 cases), BCOR (3 cases), DNMT3A (3 cases), STAG2 (2 cases), IDH1/2 (2 cases), and TET (2 cases). Among the 13 patients with detectable mutations, 12 patients achieved composite response (CR+CRi). The average recovery time of white blood cell count was 14.6 days after chemotherapy, and the average recovery time of platelets was 7.7 days after chemotherapy. The main adverse event was myelosuppression, with 10 patients accompanied by infection. Except for 1 patient who died due to septic shock during chemotherapy, no patients experienced serious complications such as heart, liver, or kidney damage during the treatment process. CONCLUSION The CACAG+V regimen, which combines the CAG regimen with venetoclax, chidamide, and azacitidine, can be applied in the treatment of elderly AML patients, demonstrating good safety and induction remission rate.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Azacitidine/therapeutic use* ; Aged ; Benzamides/therapeutic use* ; Male ; Female ; Treatment Outcome ; Middle Aged ; Cytarabine ; Aclarubicin ; Granulocyte Colony-Stimulating Factor

Sucrose synthase plays a crucial role in the plant sugar metabolism pathway by catalyzing the production of uridine diphosphate (UDP)-glucose, which serves as a bioactive glycosyl donor for various metabolic processes. In this study, a sucrose synthase gene named CtSus was cloned from Cistanche tubulosa, a traditional Chinese medicine known for its rich content of diverse glycosides, based on transcriptome analysis results. The open reading frame of CtSus was 2 418 bp long encoding 805 amino acids. Sequence analysis revealed conserved domains associated with the plant sucrose synthase family at both the N-terminal and C-terminal regions of CtSus protein. Phylogenetic analysis demonstrated that CtSus shares a close evolutionary relationship with sucrose synthases from other plants within the same order. Functional identification of CtSus was performed through whole-cell catalysis coupling with UGT71BD1, a characterized glycosyltransferase enzyme. The results showed that the introduction of CtSus significantly enhanced the conversion rate of glycosylation catalyzed by UGT71BD1. The soluble expression of CtSus in Escherichia coli was further achieved using the pCold^TM TF expression vector. In vitro enzymatic assay indicated the activity of CtSus to catalyze the formation of UDP-glucose in the presence of sucrose and UDP. Real-time quantitative-polymerase chain reaction results showed that the expression patterns of CtSus gene in different parts of C. tubulosa and the suspension cell cultures of C. tubulosa under drought stress correlated with the accumulation patterns observed for phenylethanol glycosides, respectively. Furthermore, key amino acids and their interactions between enzyme and substrate were explored based on protein structure prediction and molecular docking results. Overall, our findings identify a sucrose synthase CtSus responsible for the supply of the active glycosyl donor UDP-glucose during the biosynthesis of glycoside products in C. tubulosa and have also provided a gene element that can be utilized in engineering strain construction for glycoside products production.

Assessment is an indispensable and critical activity in the educational process. In the recent decades, with the birth and development of competence-based educational paradigm, the rationale behind assessment is shifting from "assessment of learning" to "assessment for learning". Workplace-based assessment (WPBA), which aims to improve the quality of both learning and teaching through assessment in real workplace circumstances, is a set of assessment tools that conforms to the new concepts of medical education. In this article, with the purpose to promote the application of WPBA and thus enhance the quality of dental education in our country, a thorough discussion is performed regarding the core principles, tools, advantages of WPBA as well as attentions that should be noted when applying WPBA. It is recommended to establish a longitudinal assessment system which employs various WPBA tools and assesses the development of students' competencies through the whole educational process. Such a dynamic assessment system may be helpful to provide all-rounded and competent dental talents who can eventually benefit the society.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.

Objective:To construct a predictive model for intensive care unit (ICU) and in-hospital mortality risk in patients with traumatic brain injury (TBI) and validate its performance.Methods:A retrospective cohort study was conducted to analyze the clinical data of 3 907 patients with TBI published until May 2018 in the eICU Collaborative Research Database v2.0 (eICU-CRD v2.0), including 2 397 males and 1 510 females, aged 18-92 years [63.0(43.0, 79.0)years]. According to whether the patients died in ICU or at hospital stay, they were divided into ICU survival group ( n=3 575) and ICU mortality group ( n=332), and hospital survival group ( n=3 413) and hospital mortality group ( n=494). The general data, admission diagnosis, laboratory tests, therapeutic interventions, and clinical outcomes were extracted as variables of interest. Univariate analysis and multivariate Logistic regression analysis were conducted on both the survival groups and the mortality groups to identify the independent risk factors that affect ICU and in-hospital mortality in TBI patients, based on which a Logistic regression prediction model was constructed and represented by Nomograms. The extracted dataset was randomly divided into training set ( n=2 735) and validation set ( n=1 172) with a ratio of 7∶3, and was applied for internal validation of the of the predictive model. Meanwhile, the data of TBI patients in the MIMIC-III v1. 4 database were extracted for external validation of the predictive model. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used for discriminability evaluation of the model, and the Hosmer-Lemeshow (H-L) goodness of fit test and calibration curve were used for calibration evaluation of the model. Results:The statistically significant variables identified in the univariate analysis were included in the multivariate logistic regression analysis of ICU mortality and in-hospital mortality risk. The results revealed that acute physiology and chronic health evaluation IV (APACHE IV) score ( OR=1.04, 95% CI 1.03, 1.04, P<0.01), Glasgow coma scale (GCS) ( OR=0.66, 95% CI 0.59, 0.73, P<0.01), cerebral hernia formation ( OR=6.91, 95% CI 3.13, 15.26, P<0.01), international normalized ratio (INR) ( OR=1.33, 95% CI 1.09, 1.62, P<0.01), use of hypertonic saline ( OR=0.45, 95% CI 0.21 0.94, P<0.05), and use of vasoactive agents ( OR=2.19, 95% CI 1.36, 3.52, P<0.01) were independent risk factors for ICU mortality in TBI patients. The age (with 10 years as a grade) ( OR=1.28, 95% CI 1.17, 1.40, P<0.01), APACHE IV score ( OR=1.03, 95% CI 1.02, 1.04, P<0.01), GCS ( OR=0.75, 95% CI 0.71, 0.80, P<0.01), cerebral hernia formation ( OR=6.44, 95% CI 2.99, 13.86, P<0.01), serum creatinine level ( OR=1.07, 95% CI 1.01, 1.15, P<0.05), INR ( OR=1.49, 95% CI 1.20, 1.85, P<0.01), use of hypertonic saline ( OR=0.41, 95% CI 0.21, 0.80, P<0.01), and use of vasoactive agents ( OR=2.27, 95% CI 1.46, 3.53, P<0.01) were independent risk factors of in-hospital mortality of TBI patients. Based on the forementioned independent risk factors for ICU mortality, the model equation was constructed: Logit P (ICU)=7.12+0.03×"APACHE IV score"-0.42×"GCS"+1.93×"cerebral hernia formation"+0.28×"INR"-0.81×"use of hypertonic saline"+0.79×"use of vasoactive agents". Based on the forementioned independent risk factors for in-hospital mortality, the model equation was constructed: Logit P (in-hospital)=2.75+0.25×"age"(with 10 years as a grade)+0.03×"APACHE IV score"-0.28×"GCS"+1.86×"cerebral hernia formation"+0.07×"serum creatinine level"+0.40×"INR"-0.90×"use of hypertonic saline"+0.82×"use of vasoactive agents". In the prediction model for ICU mortality, the AUC of the training set and validation set was 0.95 (95% CI 0.94, 0.97) and 0.91 (95% CI 0.87, 0.95). The result of H-L goodness of fit test of the training set was P=0.495 with the average absolute error in the calibration curve of 0.003, while the result of H-L goodness of fit test of the validation set was P=0.650 with the average absolute error in the calibration curve of 0.012. In the prediction model for in-hospital mortality, the AUC of the training set and validation set was 0.91 (95% CI 0.89, 0.93) and 0.91(95% CI 0.88, 0.94). The result of H-L goodness of fit test of the training set was P=0.670 with the average absolute error in the calibration curve of 0.006, while the result of H-L goodness of fit test of the validation set was P=0.080 with the average absolute error in the calibration curve of 0.021. In the external validation set of ICU mortality risk, the AUC of the prediction model was 0.88 (95% CI 0.86, 0.90), while the result of H-L goodness of fit test was P=0.205 with the average absolute error in the calibration curve of 0.031. In the external validation set of in-hospital mortality risk, the AUC of the prediction model was 0.88 (95% CI 0.85, 0.91), while the result of H-L goodness of fit test was P=0.239 with the average absolute error in the calibration curve of 0.036. The internal and external validation of the model indicated that both the prediction models for ICU and in-hospital mortality had good discriminability and calibration. Conclusion:The ICU mortality prediction model constructed by APACHE IV score, GCS, cerebral hernia formation, use of hypertonic saline, vasoactive agents use of and INR, and the in-hospital mortality prediction model constructed by age grading, APACHE IV score, GCS, cerebral hernia formation, serum creatinine level, hypertonic saline use of, use of vasoactive agents and INR can predict the mortality risk of TBI patients well.

AIM To control the quality of Bupleurum chinense DC.METHODS The analysis was performed on a 35℃ thermostatic Venusil XBP C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-water flowing at 1.0 mL/min,and the detection wavelength was set at 210 nm.The HPLC fingerprints were established,after which the contents of saikosaponin A,saikosaponin B2,saikosaponin C,saikosaponin D,saikosaponin E,saikosaponin F and 6″-O-acetylsaikosaponin A were determined,and principal component analysis was made.RESULTS There were thirteen common peaks in the fingerprints for twelve batches of medicinal materials with the similarities of 0.970-0.995.Seven constituents showed good linear relationships within their own ranges(R2≥0.999 8),whose average recoveries were 90.75%-100.91% with the RSDs of 1.6%-4.0% .Various constituents demonstrated similar contents in medicinal materials originated in Inner Mongolia and Shanxi.CONCLUSION This precise,accurate and stable method can be used for the quality evaluation of B.chinense.

Objective:To explore the association between triglyceride-glucose (TyG) index and carotid artery plaque in patients with type 2 diabetic kidney disease (DKD).Methods:Clinical data of 620 DKD patients admitted in the Department of Endocrinology, the Affiliated Huai′an First People′s Hospital of Nanjing Medical University from August 2018 to August 2022 were retrospectively analyzed, including 366 cases with carotid artery plaque and 254 cases without carotid plaque. According to TyG index quartile patients were divided into Q 1,Q 2, Q 3 and Q 4 groups with TyG index<8.94,≥8.94 and<9.44,≥9.44 and<9.96, and≥9.96, respectively. The prevalence of carotid plaque in DKD patients with different TyG index levels was analyzed. The relationship between TyG index and carotid plaque occurrence in DKD patients were analyzed with Logistic regression analysis and restricted cubic lines (RCS). Results:The age, course of disease, smoking rate, SBP, HbA1c, TG, BUN, eGFR and TyG indexes in carotid plaque group were significantly higher than those in non-carotid plaque group (all P<0.05). Binary logistic regression analysis showed that age, disease course, smoking rate, SBP, HbA1c, TG, BUN, low eGFR and TyG index were independent influencing factors for carotid plaque ( OR=1.05, 1.05, 1.88, 1.01, 1.09, 1.11, 1.09, 0.99 and 1.28, all P<0.05). The risk of carotid plaque in DKD patients in Q 3 and Q 4 groups was 2.20 and 2.50 times higher than that in Q 1 group. After adjusting for age, sex, course of disease, smoking, BMI, blood pressure (SBP and DBP), blood lipids (TC, HDL and LDL) and renal function, the risk of carotid plaque in DKD patients in Q 3 and Q 4 groups was higher than that in Q 1 group ( OR=1.95 and 2.24). RCS analysis showed that the correlation between TyG index and the risk of carotid plaque in DKD patients was linear(χ 2=0.40, P=0.527), and DKD patients with TyG index>9.95 had a higher risk of carotid plaque. Conclusions:TyG index is significantly elevated in DKD patients with carotid plaque, and TyG index is an independent risk factor for the occurrence of carotid plaques in DKD patients.