Two new flavonoid glycosides from Diphylleia sinensi / 药学学报

Five flavonoid glycosides were isolated from the methanol and ethyl acetate fractions of the ethanol extract of Diphylleia sinensi by using various chromatographic methods, including silica gel, MCI gel, Sephadex LH-20, ODS and semi-preparative HPLC. The structures of the isolated compounds were identified as diphyflavonoid A (1), diphyflavonoid B (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4), kaempferol-3-O-(6″-O-acetyl)-β-D-glucopyranoside (5) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, and MS). Compounds 1 and 2 were two new flavonoid glycosides, and compounds 3 and 5 were isolated from the genus Diphylleia for the first time.

Synthesis and biological activity evaluation of phthalimide-donepezil hybrids / 药学学报

A series of phthalimide-donepezil (PTA-DPZ) hybrids (5a-e, 6a-l) were designed, synthesized and evaluated as selective inhibitors of acetylcholinesterase (AChE). The results showed that some hybrids had strong AChE inhibitory activity with half maximal inhibitory concentration (IC50) at nanomolar range, which was better than the control drugs galanthamine and tacrine, and equivalent to DPZ. Compound 6k exhibited the strongest inhibition to AChE with an IC50 value of 0.13 μmol·L-1. Kinetic and molecular modeling studies showed that 6k targeted both catalytic active site and peripheral anionic site of AChE. Moreover, some compounds could inhibit AChE-induced β-amyloid (Aβ) aggregation. In addition, absorption, distribution, metabolism and excretion prediction results showed 6k conforms to the Lipinski's rule of five and had high partition coefficient P value. These compounds, especially 6k, may be considered as a dual-functional lead compound for in-depth research.

Thinking of Traditional Chinese Medicine in Prevention and Treatment of Panvascular Diseases Based on ''Blood Vessel-Zangfu Organ-Syndrome Differentiation and Treatment'' / 中国实验方剂学杂志

The term ''panvascular'' refers to the human vascular system， which is a complex network of arteries， veins， and lymphatic vessels. Panvascular diseases refer to a group of vascular system diseases， with vascular atherosclerosis as the common pathological feature. The panvascular diseases in target organs such as the heart， brain， kidney， and limbs are caused by ischemia or bleeding， including arterial system diseases， venous system diseases， microcirculation system diseases， and Zangfu organ-blood vessel diseases. The concept of panvascular diseases integrates vascular lesions and target organ damage. In clinical practice， blood vessels in multiple regions are regarded as a large vascular unit system， and vascular lesions and the induced target organ damage are considered as a whole. Based on the holistic concept and the Zangxiang theory in traditional Chinese medicine （TCM）， the ''blood vessel-Zangfu organ-syndrome differentiation and treatment'' network is built， on the basis of which a pattern of vascular disease-Zangfu organ dysfunction-syndrome differentiation and treatment is applied to the TCM diagnosis and treatment of panvascular diseases. The theory of treating arterial system diseases from the heart， venous system diseases from the kidneys， and microvascular system diseases from the liver is proposed. According to the causes identified based on syndrome differentiation， this paper summarizes the methods of reinforcing Yang and activating blood （including warming Yang and activating blood， replenishing Qi and activating blood， replenishing Qi， nourishing Yin and activating blood， activating Yang and blood， dispersing cold and activating blood）， cooling blood and resolving stasis， tonifying kidney and promoting urination coupled with activating blood and dredging vessels， nourishing Yin and tonifying kidney coupled with activating blood and dredging vessels， and soothing liver and regulating Qi coupled with activating blood and dredging collaterals， as well as wind-extinguishing medicines， applied to the treatment of panvascular diseases， aiming to provide methods and ideas for the treatment of vascular diseases with TCM.

Effect of miR-141-5p/ZNF705A on adhesion of bone marrow mesenchymal stem cells in chronic myeloid leukemia cell-derived exosomes / 中国药理学通报

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism / 中国药房

OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene pharm_chenjing@163.com family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （P＜ 0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （P＜0.01）. CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.

Advance of research on Hereditary spastic paraplegia type 4 / 中华医学遗传学杂志

Spastic paraplegia type 4 (SPG4) is the most common type of autosomally inherited spastic paraplegia. Its main clinical features include typical simple hereditary spastic paraplegia, with neurological impairments limited to lower limb spasticity, hypertonic bladder dysfunction, and mild weakening of lower limb vibration sensation, without accompanying features such as nerve atrophy, ataxia, cognitive impairment, seizures, and muscle tone disorders. SPAST is the main pathogenic gene underlying SPG4, and various pathogenic SPAST variants have been discovered. This disease has featured a high degree of clinical heterogeneity, and the same pathogenic variant can have different age of onset and severity among different patients and even within the same family. There is a lack of systematic research on the correlation between the genotype and phenotype of SPG4, and the pathogenic mechanism has remained controversial. This article has provided a review for the clinical characteristics, pathogenic gene characteristics, correlation between the genotype and phenotype, and pathogenic mechanism of this disease, with an aim to provide reference for its clinical diagnosis and treatment.

Application of Insect Medicines in Treatment of Coronary Microvascular Dysfunction Based on Comorbidity Theory of "Blood-Vessel-Cardiac Collaterals" / 中国实验方剂学杂志

Coronary microvascular dysfunction （CMD） is one of the important causes of myocardial ischemia and non-obstructive coronary artery ischemic symptoms. However， effective diagnostic methods and targeted treatment strategies for CMD are currently lacking. According to traditional Chinese medicine （TCM）， the comorbidity theory of "blood-vessel-cardiac collaterals" plays a central role throughout the entire development process of CMD. It suggests that in the clinical diagnosis and treatment of CMD， the treatment of blood， vessels， and cardiac collaterals should not be neglected. In light of this， insect medicines， known for their efficacy in promoting blood circulation， resolving stasis， and alleviating spasms， hold promise as a potential treatment for CMD. However， there is currently no research or summary on the use of insect medicines for the treatment of CMD. Therefore， this article took the comorbidity theory of "blood-vessel-cardiac collaterals" as the starting point and divided the pathogenesis of CMD into five evolution stages： Beginning in the blood （changes in blood components and hemorheology）， progressing in the vessels （atheromatous plaque formation and unstable plaques）， occurring in the cardiac collaterals （microvascular endothelial damage and microvascular constriction and spasms）， ending in the cardiac collaterals （microvascular remodeling）， and resulting in energy metabolism disorders throughout the process， so as to explore the pathogenesis and evolution of CMD. In addition， based on the modern pharmacological research on insect medicines， this article discussed the clinical application of insect medicines in the treatment of CMD from four aspects： Promoting blood circulation and removing blood stasis to relieve vessels' obstruction， relieving spasms to alleviate pain， combating poison with poison to disperse stagnation， and tonifying cardiac collaterals to nourish the heart， which aims to provide a theoretical basis for the use of TCM in treating CMD， broaden the scope of medication， and improve clinical efficacy.

Epidemiological characteristics of pulmonary tuberculosis in the elderly people in Wuhan in 2016-2020 / 公共卫生与预防医学

Objective To analyze the epidemiological characteristics of pulmonary tuberculosis in the elderly people in Wuhan during 2016-2020, and to provide a basis for formulating effective prevention and control strategies and measures. Methods Using the National Tuberculosis Information Management System, a descriptive statistical analysis was performed on the medical records of elderly (≥60 years old) pulmonary tuberculosis patients registered in Wuhan from 2016 to 2020. Results A total of 9 427 elderly pulmonary tuberculosis patients were registered in Wuhan during 2016-2020, accounting for 32.07% of the total number of registrations in the whole population. The reported incidence rate of tuberculosis in the elderly was significantly higher than that in the total population, and the reported incidence rates in both the elderly and the general population showed declining trends (whole population χ2trend=216.97, P2trend=153.57, P<0.05). The time distribution showed that more cases occurred from April to November (70.90%). The top three districts with the largest number of registered cases were far urban areas, namely Huangpi District (13.81%), Xinzhou District (11.55%), and Jiangxia District (9.82%). The ratio of male to female with pulmonary tuberculosis in elderly patients was 2.85:1. Among the elderly pulmonary tuberculosis, the most registered cases were in the age group of 60 ~ years old, followed by 65 ~ years old. The proportion of smear-positive in elderly patients with pulmonary tuberculosis retreatment was 16.83%. Conclusion From 2016 to 2020, the epidemic situation of elderly pulmonary tuberculosis showed a downward trend in Wuhan. However, the elderly population with tuberculosis registrations still accounted for a relatively high proportion of the total population. According to the epidemiological characteristics of pulmonary tuberculosis among the elderly, the city should carry out tuberculosis prevention and control work in a timely, appropriate and focused manner.

Extracellular Expression and Purification of Spider Neurotoxin Hainantoxin-IV in Escherichia coli / 中国生物化学与分子生物学报

The spider neurotoxin hainantoxin-IV(HNTX-IV), which is isolated from the crude venom of the spider Selenocosia hainana, can specifically inhibit the tetrodotoxin-sensitive(TTX-S) sodium channel, and can selectively inhibit Voltage-gated sodium channel(VGSC) Na

Six-week Aerobic Exercise Improves Oxidative Damage of Skeletal Muscles and Promotes Myokine Production in Atherosclerotic Mice / 中国生物化学与分子生物学报

Atherosclerosis involving peripheral arteries can cause skeletal muscle lesions, in which oxidative damage is an important manifestation, and atherosclerosis also reduces the production and secretion of beneficial myokines. Irisin, musclin and β-aminoisobutyric acid (BAIBA) are thought to be involved in improving atherosclerosis. However, the molecular mechanism of atherosclerosis-induced skeletal muscle lesions and the effects of aerobic exercise training on the oxidative damage of skeletal muscle and myokine production remain unclear. In this study, apolipoprotein E knockout (ApoE

Research progress of nuclear factor erythroid 2-related factor 2 in pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a common chronic interstitial lung disease. It is characterized by excessive deposition of extracellular matrix and remodeling of lung tissue structure, resulting in severe impairment of lung function. The cause of its pathogenesis is still unclear. Therefore, it is urgent to explore its pathogenesis and find new targets to combat pulmonary fibrosis. Studies have shown that nuclear factor erythroid 2-related factor 2 can maintain the body's redox homeostasis by regulating antioxidant genes and combining antioxidant response components, thereby protecting tissues and cells from oxidative stress. In recent years, many studies have proved that nuclear factor erythroid 2 -related factor 2 can play an anti-fibrotic role by alleviating oxidative stress, inhibiting macrophage polarization, activating autophagy, inhibiting ferroptosis, and blocking epithelial-mesenchymal transition. This paper provides a brief review of the association and research progress of nuclear factor erythroid 2-related factor 2 with pulmonary fibrosis, with the aim of providing a new direction for the precise treatment of pulmonary fibrosis.

Research progress of metformin in the pathogenesis of pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a chronic, progressive and irreversible respiratory disease characterized by hyperposition of extracellular matrix leading to inflammation and extensive lung remodeling. There is currently no effective treatment. Multiple studies have shown that metformin is a classic antiglycemic drug with antifibrotic potential. However, at present, there is no consensus on the specific mechanism of metformin's anti-fibrosis effect, and this paper reviews the research progress of metformin in the field of pulmonary fibrosis in recent years, mainly from IGF-1/IGF-1R/PI3K signaling, AMPK/mTOR signaling, TGF-β/Smad signaling pathway, and intervening in myofibroblast proliferation and apoptosis, improving oxidative stress, inhibiting epithelial interstitial transformation and transglutaminase. In order to be able to more deeply and comprehensively understand the antifibrosis mechanism and clinical application scope of metformin in the future, and provide new ideas for the treatment of pulmonary fibrosis.

The therapeutic effect of Balanophora polysaccharide on acetic acid gastric ulcer in rats and its mechanism / 中国药理学通报

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.

COVID-19-mediated pulmonary fibrosis: from mechanisms to medicines / 中国药理学通报

Coronavirus disease-19 (COVID-19), a global epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to lung injury in millions of people. SARS-CoV-2 can not only cause cytokine storm, acute respiratory distress syndrome and respiratory failure in the phase of acute infection, but also have potential long-term effects on the lungs. Survivors of severe COVID-19 may develop pulmonary fibrosis, resulting in permanent lung injury. In this review we expound the occurrence and development of COVID-19-related pulmonary fibrosis, summarize the key roles of TGF-p/Smad, TGF-fV MAPK, JAK/STAT, Wnt/(3-catenin, YAP/TAZ, NF-KB and PI3K/Akt signal pathways in this process, and analyze the advantages and disadvantages of antiviral drugs, anti-fibrosis drugs, cytokine-targeted drugs, corticosteroids, spironolactone, traditional Chinese medicine prescriptions and lung transplantation in its treatment. This review may provide a reference for the study of pathological mechanism and clinical treatment of COVID-19-re-lated pulmonary fibrosis.

Effects of different extraction parts of Tibetan medicine Pulicaria insignis Drumm ex Dunn on CIA rats / 中国药理学通报

Aim To clarify the anti-rheumatoid arthritis effect of Tibetan medicine Pulicaria insignis (P. insignis),sift out the active parts against rheumatoid arthritis,and investigate the mechanism. Methods Rat rheumatoid arthritis (CIA) model was established with bovine type II collagen and incomplete Freund's adjuvant. The effects of the total extract of P. insignis, macroporous resin eluted parts with different concentrations of ethanol and Tripterygium Glycosides (GTW) on the degree of foot swelling in CIA rats were observed,the levels of tumor necrosis factor (TNF-α), intd rheumaerleukin-1β (IL-1β) antoid factor (RF) in serum of rats were detected, the pathological changes of synovial tissues were investigated, and the effects on MAPK/p38/NF-κB, TLR4/NF-κB protein expressions were explored by Western blot. Results Compared with the model group, the total extract of P. insignis and the eluted part of macroporous resin 60% ethanol could significantly reduce the degree of joint swelling in CIA rats, effectively improve the pathological changes of rats synovium tissues, and significantly reduce the levels of rat tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and rheumatoid factor (RF) in serum inflammatory factors, and markedly decrease the expression of related inflammatory proteins (TLR4, NF-κB, Myd88, p-p38, p-IκBα, iNOS, etc) in synovial tissue. Conclusions (1) P. insignis can relieve the symptoms of joint inflammation in rats with rheumatoid arthritis, and the eluted part of macroporous resin 60% ethanol of P. insignis is the effective active part for anti-rheumatoid arthritis. (2) The total and partial extracts of P. insignis can relieve arthritis symptoms in CIA rats through inhibiting the MAPK/ p38/NF-κB and TLR4/NF-κB signaling pathways.

Circular RNA ame_circ_000115 regulates expression of genes in larval gusts of Apis mellifera ligustica stressed by Ascosphaera apis / 生物工程学报

Circular RNAs (circRNAs) are a new class of non-coding RNAs, which have been confirmed to regulate insect gene expression and immune response through multiple manners such as competing endogenous RNA (ceRNA) regulatory network. Currently, function of circRNA in honey bee immune response remains unclear. In this study, PCR and Sanger sequencing were performed to validate the back splicing (BS) site of ame_circ_000115 (in short ac115). RT-qPCR was used to detect the expression profile of ac115 in larval guts of Apis mellifera ligustica stressed by Ascosphaera apis. Dual-luciferase reporter gene assay was conducted to verify the binding relationship between ac115 and ame-miR-13b. Interference of ac115 in larval guts was carried out by feeding specific siRNA, followed by determination of the effect of ac115 interference on expression of six genes relevant to host immune response. The results confirmed the existence of BS site within ac115. Compared with the un-inoculated group, the expression of ac115 in 4-day-old larval gut of the A. apis-inoculated group was up-regulated with extreme significance (P < 0.000 1), while that in 5- and 6-day-old larval guts were significantly up-regulated (P < 0.05). The brightness of specific band for ac115 in 4-, 5- and 6-day-old larval guts of the siRNA-circ_000115-fed group gradually became weak, whereas that of the siRNA-scrambl-fed group was pretty high without obvious variation. Compared with that of the siRNA-scramble-fed group, the expression of ac115 in 4-day-old larval gut of the siRNA-circ_000115-fed group was significantly down-regulated (P < 0.05), whereas that of the 5- and 6-day-old larval guts were down-regulated with extreme significance (P < 0.001). Ame-miR-13b was truly existed and expressed in A. m. ligustica larval guts, and there was true binding relationship between ac115 and ame-miR-13b. Compared with that of the siRNA-scramble-fed group, the expression of antimicrobial peptide genes hymenoptaecin and abaecin in 6-day-old larval gut of the siRNA-circ_000115-fed group was significantly up-regulated (P < 0.05), while that of ecdysone receptor (Ecr) was down-regulated with extreme significance (P < 0.01). These results indicate that ac115 is truly expressed in A. m. ligustica larval guts, BS site truly exists within ac115, and effective interference of ac115 in A. m. ligustica larval guts can be achieved via feeding siRNA. Moreover, ac115 potentially regulates Ecr expression through adsorption of ame-miR-13b and expression of hymenoptaecin and abaecin using a non-ceRNA manner, further participating in host stress-response.

Clinical characteristics of children infected with SARS-CoV-2 Omicron variant combined with allergic disease / 中华儿科杂志

Objective: To investigate the clinical characteristics of children with allergic diseases suffering from SARS-CoV-2 Omicron variant strains. Methods: This was a cross-sectional study. A total of 43 pediatric patients with allergic diseases infected by SARS-CoV-2 from April 25, 2022 to June 8, 2022 in Shanghai Jiao Tong University School of Medicine were selected as the allergic disease group, while 114 cases without underlying diseases and 16 cases with other underlying diseases were selected as control groups diagnosed at the same period. Clinical data including clinical features, laboratory tests, duration of hospitalization, and the time to negative turn of novel coronavirus nucleic acid were collected and analysed. Kruskal-Wallis H test, chi-square test or Fisher exact test were used for comparison among three groups. Results: Among the 43 patients with allergic diseases, 28 were males and 15 were females, with an age of 4.4 (2.1, 8.2) years on admission, including 32 mild cases and 11 common cases. The allergic disease group included 20 cases (46.5%) of atopic dermatitis and eczema, followed by 14 cases (32.6%) of rhinitis, 8 cases (18.6%) of food allergies, 7 cases (16.3%) of asthma, 4 cases (9.3%) of allergic conjunctivitis and 2 cases (4.7%) of drug allergy. Among the 114 cases without underlying diseases, 57 were males and 57 were females, with an age of 2.8 (1.2, 5.6) years on admission, including 93 mild cases and 21 common cases. Among the 16 cases with other underlying diseases, 9 were males and 7 were females, with an age of 3.0 (2.6, 10.8) years on admission, including 13 cases mild and 3 cases common cases. Children with allergic diseases had higher frequency of sore throat and vomiting than those without underlying diseases (10 cases (23.3%) vs.9 cases (7.9%), 14 cases (32.6%) vs. 11 cases (9.6%), χ²=6.93, 12.24, both P<0.05). The lymphocyte count of patients with allergic disease was lower than those without underlying disease (1.1 (0.7,1.7)×109 vs. 1.6 (1.1,2.7)×109/L, H=-28.00,P=0.005). There were no significant differences in age, gender, typing of SARS-CoV-2, the duration of hospitalization, cycle threshold values of SARS-CoV-2 and the time to negative turn of novel coronavirus nucleic acid among the three groups (all P>0.05). Conclusions: Children with allergic diseases may suffer from sore throat and vomiting more frequently when infected with SARS-CoV-2 Omicron variant. The combination of allergic diseases hardly influenced the disease course of SARS-CoV-2 in children.

Responses of blood parameters and hemoglobin subtypes in plateau zokors and plateau pikas to different altitude habitats / 生理学报

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α2β2 and fetal α2ε2 hemoglobins were identified, while erythrocytes of plateau zokors only had adult α2β2 hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.

Establishment and validation of a multigene model to predict the risk of relapse in hormone receptor-positive early-stage Chinese breast cancer patients / 中华医学杂志(英文版)

BACKGROUND@#Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery.@*METHODS@#In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC).@*RESULTS@#A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model.@*CONCLUSIONS@#A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.

Molecular genetic characteristics of a family which coinheritance of rare-88 C>G (HBB:c.-138 C>G) β-thalassemia mutation with α-thalassemia and review of the literature / 中华预防医学杂志

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) β-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑwsɑ/ɑɑ) and β-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (β-88 C>G/βN). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.