Controllable construction of ZIF-derived Co9S8 hollow polyporous polyhedrons with Ru-doping for enhanced hydrogen evolution reaction.

Ru-doped Co9S8 hollow porous polyhedrons (Ru-Co9S8 HPPs) derived from zeolitic-imidazolate-frameworks were synthesized through hydrothermal coprecipitation and thermal decomposition methods. The results indicate that Ru-Co9S8-500 HPPs possess a strong Ru-Co synergistic effect, large electrochemical surface area, and sufficient active sites, endowing them with excellent hydrogen evolution reaction performance.

Danggui-Shaoyao San alleviates cognitive impairment via enhancing HIF-1α/EPO axis in vascular dementia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Invigorating blood circulation to remove blood stasis is a primary strategy in TCM for treating vascular dementia (VaD). Danggui-Shaoyao San (DSS), as a traditional prescription for neuroprotective activity, has been proved to be effective in VaD treatment. However, its precise molecular mechanisms remain incompletely understood. AIM OF THE STUDY: The specific mechanism underlying the therapeutic effects of DSS on VaD was explored by employing network pharmacology as well as in vivo and in viro experiment validation. MATERIALS AND METHODS: We downloaded components of DSS from the BATMAN-TCM database for target prediction. The intersection between the components of DSS and targets, PPI network, as well as GO and KEGG enrichment analysis were then performed. Subsequently, the potential mechanism of DSS predicted by network pharmacology was assessed and validated through VaD rat model induced by 2VO operation and CoCl2-treated PC12 cells. Briefly, the DSS extract were first quantified by HPLC. Secondly, the effect of DSS on VaD was studied using MWM test, HE staining and TUNEL assay. Finally, the molecular mechanism of DSS against VaD was validated by Western blot and RT-QPCR experiments. RESULTS: Through network analysis, 137 active ingredients were obtained from DSS, and 67 potential targets associated with DSS and VaD were identified. GO and KEGG analysis indicated that the action of DSS on VaD primarily involves hypoxic terms and HIF-1 pathway. In vivo validation, cognitive impairment and neuron mortality were markedly ameliorated by DSS. Additionally, DSS significantly reduced the expression of proteins related to synaptic plasticity and neuron apoptosis including PSD-95, SYP, Caspase-3 and BCL-2. Mechanistically, we confirmed DSS positively modulated the expression of HIF-1α and its downstream proteins including EPO, p-EPOR, STAT5, EPOR, and AKT1 in the hippocampus of VaD rats as well as CoCl2-induced PC12 cells. HIF-1 inhibitor YC-1 significantly diminished the protection of DSS on CoCl2-induced PC12 cell damage, with decreased HIF-1α, EPO, EPOR expression. CONCLUSION: Our results initially demonstrated DSS could exert neuroprotective effects in VaD. The pharmacological mechanism of DSS may be related to its positive regulation on HIF-1α/EPO pathway.

Dendrobium Officinale Polysaccharide Alleviates Hepatic Fibrosis via Epithelial-Mesenchymal Transition / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of Dendrobium officinale polysaccharide （DOP）on CCl4-induced hepatic fibrosis（HF）and its mechanism. MethodsA total of 56 male SD rats were randomly divided into seven groups： normal group（NG），model group（MG），colchicine group（CG， 0.1 mg/kg）， Fuzheng Huayu group（FG， 0.45 g/kg），low-dose DOP group（LDG， 0.05 g/kg），middle-dose DOP group（MDG， 0.1 g/kg）and high-dose DOP group（HDG，0.2 g/kg），with 8 rats in each group. HF rat model was established by subcutaneous injection with 40% CCl4 olive oil mixture， every 3-day for 10 weeks. At the end of the sixth week， the drug groups were treated with colchicine， Fuzheng Huayu and DOP solution by gavage respectively， once a day for 4 weeks. NG and MG groups were similarly handled with an equal amount of 0.9 % normal saline. Liver histopathology was detected using hematoxylin-eosin （HE）， Masson and Sirius red staining； blood biochemistry was tested for liver function and four indicators of HF； RT-qPCR and Western Blot were used to measure the expression of α-SMA， Col-I， E-cadherin， and ZEB1 genes and proteins in the liver tissues of rats， respectively. ResultsHE， Masson， and Sirius red staining showed that the liver tissue of MG rats had typical pathologic features of HF， and the degree of HF was alleviated in LDG， MDG， and HDG rats， respectively. Liver function test results showed that the serum AST， TBIL， and AKP levels were significantly lower in LDG， MDG， and HDG， compared with those of the MG （P < 0.05 or < 0.01）. Meanwhile， ALT levels in serum deceased remarkably except in LDG （P < 0.05 or < 0.01）. The four results of HF showed that the serum HA， LN， PC-Ⅲ， and COL-Ⅳ levels in LDG， MDG， and HDG rats were significantly decreased compared with those of the MG （P < 0.05 or < 0.01）. The relative expressions of α-SMA， COL-I， and ZEB1 genes and proteins were significantly decreased in the liver tissues of LDG， MDG， and HDG （P < 0.05 or < 0.01）， and the relative expression of E-cadherin gene and protein increased （P < 0.05 or < 0.01）. In addition， the expressions of HA， α-SMA， COL-I， ZEB1 and E-cadherin were dependent on the dose of DOP. ConclusionDOP alleviated the degree of CCl4 induced HF in rats by inhibiting the epithelial-mesenchymal transition in liver tissue.

A 1-year analysis from a natural history study in Chinese individuals with Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a disabling and life-threatening, X-linked recessive disorder caused by mutations in dystrophin. Natural history studies can inform the disease characteristics of DMD, and data from these studies can be used to plan and design clinical trials and as external controls for long-term studies. We report 12-month results from the largest natural history study of individuals with DMD in China receiving standard of care treatment. Methods: This ongoing, multicentre, prospective, single-cohort study (ClinicalTrials.gov: NCT03760029) was conducted in Chinese male participants with DMD (ambulatory aged <6 years [Group 1; n = 99]; ambulatory aged ≥6 years [Group 2; n = 177], and non-ambulatory of any age [Group 3; n = 36]. The follow-up period is ≥24 months, with some participants followed for 30 months. The primary endpoint was time to clinical milestones due to DMD disease progression, and motor, pulmonary, and cardiac function. Secondary endpoints were quality of life (QoL) assessments. Findings: Mean (standard deviation [SD]) age at screening was 3.4 (1.2), 8.6 (2.0), 12.3 (2.7) and 7.4 (3.5) years in Groups 1, 2, 3 and total respectively. Mean (SD) North Star Ambulatory Assessment (NSAA) total score at baseline was 21.2 (5.8) in Group 1, 19.5 (8.3) in Group 2 and 20.0 (7.7) in ambulatory total. Overall, the time to clinical milestones due to DMD disease progression was consistent with previous findings, in which loss of ambulation occurred at 13 years. There was a trend towards a decline over 12 months in NSAA and timed motor function from age 6 years, with the greatest reductions observed thereafter. There were no consistent trends in measures of QoL, although participants of any age generally had poorer outcomes at Month 12 versus their domain scores at baseline. Interpretation: This study improves the understanding of DMD progression according to the current standards of care in the Chinese DMD population and may inform selected endpoints and patient populations in clinical trials. Funding: Pfizer Inc.

The structural and electronic properties of (001) surface of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) with first-principles calculations.

CONTEXT: 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) is a typical insensitive energetic material. It can be used in explosive formulations, such as PBX-9502 and LX-17-0. TATB is an intriguing and unusual explosive for another reason: it crystallizes into a wide array of planar hydrogen bonds, forming a graphite-like layered structure. Therefore, TATB is one of the important research objects, and its surface structure needs to be deeply understood. In this research work, the electronic and energetic properties of TATB (001) surface are explored. METHODS: In this paper, the structural, electronic, energetic properties and impact sensitivity of TATB (001) surface structure at 0 and -3 GPa along with x-axis were calculated in this study using the first-principles calculations. The calculations in this paper are performed in the CASTEP code, which is based on the density functional theory with the first-principles calculation method using the plan-wave pseudopotential approach. The exchange-correlation interaction was adopted by the generalized gradient approximation (GGA) with the Perdew-Burke-Ernzerhof (PBE) functional. The DFT-D method with the Grimme correction accurately models van der Waals interactions. To model the surface structures of TATB, the planar slab method was employed. We constructed TATB (001) periodic slabs including three layers with a 15-Å vacuum layer.

Association of body mass index with asthma occurrence and persistence in adolescents: A retrospective study of NHANES (2011-2018).

Objective: To investigate the association of body mass index (BMI) with asthma and analyze the risk factors of asthma persistence among overweight/obese adolescents and those with a high risk for obesity. Methods: In this cross-sectional study, adolescents aged 11-17 years with complete general information and asthma diagnoses were selected from the National Health and Nutrition Examination Survey database. For adolescents without self-reported asthma, we performed matching according to age and sex at a case-to-control ratio of 1:3. Logistic regression analysis was employed to identify independent predictors of asthma occurrence followed by constructing a nomogram and comparing its efficacy to independent factors in predicting asthma occurrence. Besides, associations of BMI with asthma occurrence and persistence were evaluated. Finally, we obtained risk factors for asthma persistence in overweight/obese individuals and those at a high risk for obesity. Results: Totally 753 adolescents with asthma and 2259 adolescents without asthma were included to analyze the occurrence of asthma. BMI and Hispanic Ethnicity were independent predictors of asthma occurrence and were included in nomogram construction. BMI had an efficiency comparable to that of the nomogram model in predicting asthma occurrence, which is superior to that of Hispanic Ethnicity. Of the 753 adolescents diagnosed with asthma, 464 were still diagnosed with asthma of at least a year's duration. Interestingly, BMI may have the ability to predict asthma persistence. Further, Hispanic Ethnicity and household income were significantly related to asthma occurrence among overweight/obese and high-risk obese individuals. Conclusions: High BMI could independently predict increased asthma occurrence. Additionally, BMI may play an essential role in predicting asthma persistence. This study may help improve the diagnosis and reduce the occurrence of asthma.

Peroxido-bridged chiral double-decker dysprosium macrocycles.

Lanthanide peroxides show high reactivity in oxidative coupling of methane (OCM). However, the number of isolated and structurally characterized molecular species remains relatively small. To the best of our knowledge, homochiral molecule-based lanthanide peroxides have not been reported. Herein, two pairs of side-on peroxido-bridged dinuclear hexaazamacrocyclic dysprosium enantiomers with formulas [Dy2(LES/R)2L2O2](BPh4)2·CH3OH·CH3CN (where LE is derived from the condensation reaction between (1S,2S)/(1R,2R)-1,2-diphenylethylenediamine and 2,6-diformylpyridine; HL = 2,6-diphenylphenol) (1/2) and [Dy2(LES/R)2Cl2O2](BPh4)2·2CH3CN (3/4) are specially designed and created with the help of hydrogen peroxide. The out-of-phase alternating-current magnetic susceptibility of 1/2 gives rise to frequency-dependent peaks between 6 and 32 K under a zero applied direct current (dc) field, while no peak at any temperature and frequency was observed for 3/4 implying the presence of a weak axial crystal field (CF).

[Effects of Microplastic Exposure on the Community Structure and Function of Symbiotic Bacteria in Sinularia microclavata].

Microplastics are widely distributed in the marine environment and are harmful to the health of marine organisms (including corals). However, studies on the impact of microplastics on coral have been very limited, and the specific mechanism of their impact is not clear. Therefore, in this study, microplastic PA, which is common in the marine environment, was selected to conduct a 7-day microplastic exposure experiment on Sinularia microclavata. The effects of microplastic exposure at different times on the diversity, community structure, and function of the symbiotic bacterial community of coral were analyzed using high-throughput sequencing technology. The α-diversity of the symbiotic bacterial community of coral first decreased and then increased with the exposure time of microplastics. The analysis of ß-diversity and microbial community composition showed that microplastic exposure caused significant changes in the symbiotic bacterial community of coral, and the bacterial community composition also changed with the exposure time. A total of 49 phyla, 152 classes, 363 orders, 634 families, and 1390 genera were detected. At the phylum level, Proteobacteria was the dominant taxa in all samples, but the relative abundance varied among samples. Microplastic exposure increased the abundance of Proteobacteria, Chloroflexi, Firmicutes, Actinobacteriota, Bacteroidota, and Acidobacteriota. At the genus level, Ralstonia, Acinetobacter, and Delftia were the dominant taxa of symbiotic bacteria of coral after microplastic exposure. PICRUSt functional prediction indicated that functions of the coral symbiotic bacterial community, including signal transduction, cellular community prokaryotes, xenobiotics biodegradation and metabolism, and cell motility, decreased after microplastic exposure on coral. BugBase phenotype predictions indicated that microplastic exposure altered three phenotypes (pathogenic, anaerobic, and oxidative stress-tolerant) of the coral symbiotic bacterial community. FAPROTAX functional predictions indicated that microplastic exposure caused significant changes in functions such as the symbiotic relationship between coral symbiotic bacteria and the host, carbon and nitrogen cycling, and photosynthesis. This study provided basic data on the mechanism of microplastic impacts on corals and microplastics ecotoxicology.

Three-component acyloxylation of diazo compounds with carboxylic acids and azadienes.

Despite many studies on benzofuran-derived azadiene being reported, multi-component studies have scarcely been reported on this heterocyclic skeleton. The first cascade three-component acyloxylation of diazos with acids and azadienes has been reported under mild conditions. The reaction is applicable to various (A/A) diazo compounds, generating diverse complex benzofuran derivatives.

Role and mechanism of complement C3a receptor in the cognitive impairment of septic rats induced by cecal ligation and perforation / 解剖学报

Objective To study the role of complement C3a receptor (C3aR) in cognitive impairment in rats with sepsis induced by cecal ligation and puncture (CLP), and to explore the possible mechanism. Methods Totally 132 rats were randomly divided into sham operation group (sham group) and sepsis group (CLP group). The initial number of each group was 66 animals, and 22 animals were set at each time point. The SD rat CLP animal model was constructed, and serum and brain (hippocampus and prefrontal cortex) samples were collected at day 1, day 15 and day 30 after operation. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β) and IL-6 in the samples were determined by ELISA. Western blotting detected Tau protein (Tau), phosphorylated Taup-Tauand C3aR expression in brain samples. Totally 66 rats were randomly divided into 3 groups, sham operation group, CLP group and C3aR antagonist(C3aRa) intervention group. On 15th, 17th, and 19th days after CLP, C3aRa intervened in rats, and they received inhibition avoidance test and object recognition test 30 days after CLP. The expressions of C3aR, lonized calcium binding adapter molecule 1(Iba1), GFAP and p-Tau in the hippocampus were detected by immunofluorescence. Results Compared with the sham group, the serum and brain tissue (TNFα, IL-1β and IL-6) of rats in the CLP group first increased and then decreased within 30 days after CLP. In the hippocampus and prefrontal cortex of CLP group, Tau phosphorylation was significantly enhanced at day 30 and day 1 and 15 after surgery, respectively (P<0.05). Compared with the sham group, C3aR protein levels in hippocampus and prefrontal cortex of rats in CLP group increased significantly at day 15 and 30 after operation (P<0.05). Compared with the CLP group, the endogenous C3aR content decreased significantly after C3aRa intervention (P<0.05), and Iba1, GFAP and p-Tau immunostaining were significantly inhibited (P<0.05). The C3aRa intervention in CLP rats reversed the cognitive impairment. Conclusion C3aR plays an important role in the development of biochemical and behavioral changes commonly associated with the onset of sepsis-induced neurodegenerative processes. C3aRa can be injected into the hippocampus to counteract the neurodegenerative process induced by sepsis.

Validation of the prognostic value of the Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma: A single-center study / 中华血液学杂志

Objective: To evaluate the prognostic value of Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma (MM) . Methods: A total of 371 patients newly diagnosed with MM in Jiangsu Province Hospital were included in the study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was performed to detect cytogenetic abnormality. Clinical characteristics were combined to analyze the disease stage and evaluate the prognosis. Results: There were 37 (10.0%), 264 (71.0%), and 70 (18.8%) patients in R-ISS stage Ⅰ, Ⅱ, and Ⅲ, respectively. The median progression-free survival (PFS) times were 37, 25, and 14 months (P<0.001). The median overall survival (OS) times were not reached (NR), 66, and 30 months (P<0.001). There were 71 (19.1%), 140 (37.7%), and 160 (43.2%) patients in Mayo MASS stages Ⅰ, Ⅱ, and Ⅲ, and the median PFS times periods were 43, 27, and 19 months (P<0.001), and the median OS times were NR, NR, 35 months, respectively (P<0.001). There were, 23 (6.2%), 69 (18.6%), 222 (59.8%), and 57 (15.4%) patients in R2-ISS stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. The median PFS times were 47, 31, 25, and 15 months (P=0.001), and the median OS times were NR, NR, 49, and 55 months, respectively (P<0.001) . Conclusion: Based on the R-ISS staging system, Mayo MASS, and R2-ISS prognostic staging system incorporated 1q21+, which allows a better stratification. However, the proportion of stage Ⅲ patients in Mayo MASS and R2-ISS staging systems is relatively high, which is considered related to the high incidence of 1q21+ and ISS Ⅲ in the Chinese population.

Nanoparticles (NPs)-mediated lncBCMA silencing to promote eEF1A1 ubiquitination and suppress breast cancer growth and metastasis

Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function in vivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.

Innovation-driven trend shaping COVID-19 vaccine development in China / 医学前沿

Confronted with the Coronavirus disease 2019 (COVID-19) pandemic, China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and mutation, with several innovative platforms, which provides various technical means in this persisting combat. Derived from collaborated researches, vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19. Herein, we outline representative vaccines in multiple routes, while the merits and plights of the existing vaccine strategies are also summarized. Likewise, new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants. All in all, with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease, alongside the traditional routes, the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.

Efficacy of electroacupuncture on acute intracerebral hemorrhage and its effect on serum AQP4 in patients / 中国针灸

OBJECTIVE@#To observe the effects on neural function, living ability and mental state of the patients with acute intracerebral hemorrhage (ICH), as well as aquaporin 4 (AQP4) in the serum after treated with electroacupuncture (EA) on the base of routine therapy of western medicine.@*METHODS@#Seventy-two acute ICH patients were randomized into an observation group (36 cases, 4 cases dropped off) and a control group (36 cases, 2 cases dropped off). In the control group, the conventional treatment was delivered such as stopping bleeding, preventing re-hemorrhage, controlling blood pressure, mitigating neural edema and reducing intracranial pressure. In the observation group, on the base of the treatment in the control group, EA was supplemented. Acupoints included Shuigou (GV 26), bilateral Neiguan (PC 6) and Sanyinjiao (SP 6) etc. Electric stimulation was operated at Neiguan (PC 6) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave, and 2 Hz/100 Hz in frequency, tolerable current intensity. Electric stimulation was delivered for 30 min in each treatment, once daily and for 6 times per week. The duration of treatment was 2 weeks in the two groups. Before and after treatment, changes of the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and mini-mental state examination (MMSE), as well as AQP4 content in the serum were observed in the two groups; the efficacy and safety were compared between the two groups.@*RESULTS@#The NIHSS scores and the serum AQP4 content decreased after treatment when compared with those before treatment in the two groups (P<0.05), while, MBI and MMSE scores increased (P<0.05). In the observation group, NIHSS score and serum AQP4 content were lower than those of the control group (P<0.05), and MBI and MMSE scores were higher (P<0.05). The total effective rate of the observation group was 93.8% (30/32), higher than that of the control group (73.5%, 25/34, P<0.05). The treatment in the two groups was safe, without adverse reactions and events occurring in the patients.@*CONCLUSION@#Electroacupuncture, on the base of conventional treatment of western medicine, can effectively improve the neural function, living ability, mental state and serum AQP4 content of the patients with acute ICH. It is suggested that the effective treatment by electroacupuncture may be related to the regulation of the serum AQP4 content.

Current Status and Ethical Considerations of Data Collection and Application in Rare Disease Research / 中国医学伦理学

The research on rare diseases in China started relatively late, with scattered research resources and weak data foundation in epidemiology, diagnosis and treatment, and medication, which hinders its research progress. The rare disease data system is the foundation of rare disease research, and the ethical constraint on rare disease data collection is not only the protection of rare disease population, but also the need for the safety and quality of rare disease data. By analyzing and prospecting the current status of the construction of rare disease data systems, including the data of epidemiology, clinical diagnosis and treatment, drug trials, and follow-up to provide reference for the improvement of rare disease data systems. This paper explored the ethical issues to be followed in the process of rare disease data collection from the perspectives of justice, no harm, respect, sharing, and legalization, so as to improve the standardization of rare disease data collection and the understanding of data ethical review.

Effect and Mechanism of Cuscutae Semen Total Flavonoids Combined with Tripterygium wilfordii Polyglycoside Tablets on Ovarian Germline Stem Cells of Physiological Mice by Notch Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Cuscutae Semen total flavonoids combined with Tripterygium wilfordii polyglycoside tablets （TWPT） on ovarian germline stem cells of female physiological mice through neurogenic locus notch homolog （Notch） signaling pathway. MethodSixty female Kunming mice （5 weeks old） were randomly divided into normal group， Tripterygium wilfordii polyglycoside tablets low-， high-dose groups （13.65 mg·kg-1·d-1 and 27.3 mg·kg-1·d-1， 1 and 2 times clinical equivalent dose）， Cuscutae Semen total flavonoids low- and high-dose groups （150 mg·kg-1·d-1 and 300 mg·kg-1·d-1）， and combination group （13.65 mg·kg-1·d-1 TWPT and 150 mg·kg-1·d-1 Cuscutae Semen total flavonoids）， with 10 in each group. After 3 weeks of continuous administration， the uterus/brain and ovarian/brain indexes were calculated， and the pathological changes of ovarian tissue were observed under light microscope. The content of estradiol in serum was determined by enzyme linked immunosorbent assay （ELISA）. Immunofluorescence assay was performed to observe the expressions of germline stem cell markers in ovarian epithelium， including mouse vasa homologue （Mvh）， octamer-binding transcription factor 4 （Oct4）， tyrosine-protein kinase receptor （c-kit）， Nanog， Notch signaling pathway molecules， neurogenic locus notch homolog protein 1 （Notch1）， hes family BHLH transcription factor 1（Hes1）， and jagged canonical Notch ligand 1 （JAG1）. ResultCompared with the normal group， low and high doses of TWPT had no significant effect on the uterus/brain and ovary/brain indexes and the uterus and ovary morphologies of mice， while only the number of atretic follicles was increased （P<0.01）. The expressions of ovarian germline stem cell markers and Notch signaling pathway molecules had a decreasing trend in TWPT low-dose group， while the expressions of Mvh， c-kit， and Nanog were down-regulated （P<0.05， P<0.01） and the expressions of Notch1 and Hes1 were also reduced （P<0.01） in TWPT high-dose group. However， the above indexes were increased in Cuscutae Semen total flavonoids low-dose group （P<0.05， P<0.01）. Compared with the low does of TWPT group， the combination group had a decrease in the increased number of atretic follicles （P<0.01）， an improvement in the down-regulated expressions of Mvh and Nanog （P<0.01）， and an increase in the expressions of Notch1 and Hes1 （P<0.05， P<0.01）. ConclusionOvarian germline stem cells are the source target of the reproductive toxicity of TWPT. Cuscutae Semen total flavonoids participate in the regulation of the germline stem cell pathways to alleviate the reproductive toxicity caused by TWPT， and its mechanism of action may be related to the Notch signaling pathway.

Historical Evolution and Modern Clinical Application of Classic Formula Wuyaotang / 中国实验方剂学杂志

The classic formula Wuyaotang is the 49th of the 100 formulas in the Catalogue of Ancient Classic Prescriptions (First Batch) issued by the National Administration of Traditional Chinese Medicine, and is from the Secrets from the Orchid Chamber (《兰室秘藏》) by LI Dongyuan of the Jin Dynasty. It is composed of Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Linderae Radix, and Cyperi Rhizoma, and has the effect of moving Qi, regulating meridians, and relieving pain. It is mainly indicated for Qi stagnation and blood stasis syndrome. Based on the ancient books on Wuyaotang, this study systematically reviewed the formula source, composition, dosage, preparation, usage, functions, indications, preparation principle, drug processing, modification, etc. of Wuyaotang with the bibliometrics method, explored its historical evolution, and determined the key information. Statistical analysis of its modern literature shows that there are few studies of the original formula of Wuyaotang, and the clinical studies mainly focus on modified Wuyaotang. It has a wide range of treatment scope and can be used for the treatment of dysmenorrhea, delayed menstrual cycle, hypomenorrhea, and menstrual fever, as well as ulcerative colitis, spleen distortion, sciatica, child intestinal spasm, and other internal, surgical, gynecological, and pediatric diseases. The pathogenesis in traditional Chinese medicine (TCM) is Qi stagnation. Through the analysis and research on ancient books and modern literature recording Wuyaotang, this study is expected to provide a scientific basis for the clinical application, in-depth research, and development of the classic formula Wuyaotang.

Analysis of ARID1B gene variant in a patient with mental retardation and ejaculatory dysfunction / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a patient with mental retardation and ejaculatory dysfunction.@*METHODS@#A patient with mental retardation and ejaculatory dysfunction who was admitted to the First Affiliated Hospital of Air Force Military Medical University on November 18, 2021 was selected as the study subject. Clinical data of the patient were collected. Peripheral venous blood samples were collected from the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and the candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient, a 26-year-old male, had manifested atypical mental retardation and ejaculatory dysfunction. WES revealed that he has harbored a heterozygous variant of the ARID1B gene, namely c.5776C>T (p.Arg1926X). Sanger sequencing verified that neither of his parents has carried the same variant. The variant has been recorded in the 1000 Genomes, ExAC, gnomAD and ClinVar databases. A search of the dbSNP database suggested that the variant has a population frequency of 0.000 4%. The variant was predicted as deleterious by online software including Mutation Taster, CADD, and MutPred. Analysis with Cluster Omega online software suggested that the amino acid encoded by the variant site was highly conserved among various species. Analysis with PyMOL software suggested that the variant may affect the function of the encoded protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was predicted to be pathogenic.@*CONCLUSION@#The c.5776C>T (p.Arg1926X) variant of the ARID1B gene probably underlay the mental retardation and ejaculatory dysfunction in this patient. Above finding has broadened the spectrum of the ARID1B gene variants and provided reference for the diagnosis and treatment of the patient.

A new cinnamic acid ester derivative from Liquidambaris Resina / 中国中药杂志

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17β-hydroperoxide(4), erythrodiol(5), 13β,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3β)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) μmol·L~(-1), respectively.

Causes of Abnormal Hemoglobin Electrophoresis / 中国实验血液学杂志

OBJECTIVE@#To investigate the possible causes of abnormal hemoglobin electrophoresis results.@*METHODS@#The hemoglobin electrophoresis results of 5 696 patients in the First Affiliated Hospital of Chengdu Medical College from September 2018 to July 2021 were collected, and the abnormal results and clinical significance were analyzed.@*RESULTS@#The results of 486 patients (accounting for 8.53%) were abnormal, of which 300 cases had increased HbA2, 135 cases had decreased HbA2, 44 cases had increased F alone, and 7 cases had abnormal hemoglobin bands. Among the 486 patients, 246 patients were thalassemia gene positive (the positive rate was 50.62%), including 29 cases of α thalassemia, 208 cases of β thalassemia and 9 cases of αβ thalassemia. Among the patients with elevated HbA2, 68.67% were detected β thalassemia, 3.00% αβ thalassemia, 9.33% were suspected to be caused by macrocytosis, 6.33% by thyroid dysfunction, and 12.67% by uncertainty of the method. Among the patients with reduced HbA2, 21.48% were detected α thalassemia, 60.00% iron deficiency anemia, 8.15% were suspected to be caused by thyroid dysfunction, and 10.37% by uncertainty of the method. Among the patients with elevated F alone, the results of thalassemia gene detection were negative, 40.91% of them were suspected to be caused by macrocytosis, 27.27% by hereditary persistence of fetal hemoglobin, 29.55% by special physiological condition of pregnant women, and 2.27% by hyperthyroidism. Abnormal hemoglobin bands were detected in 7 patients, including 4 cases of hemoglobin D, 2 cases of hemoglobin E, and 1 case of hemoglobin J.@*CONCLUSION@#Thalassemia, iron deficiency anemia, macrocytosis such as megaloblastic anemia and non-severe aplastic anemia, thyroid dysfunction, hereditary persistence of fetal hemoglobin, abnormal hemoglobin diseases, the uncertainty of the method are all important causes of abnormal hemoglobin electrophoresis results. In clinical work, the patient's indicators should be comprehensively analyzed to determine the possible cause.