Causative Microorganisms Isolated from Patients with Intra-Abdominal Infections and Their Drug Resistance Profiles: An 11-Year (2011-2021) Single-Center Retrospective Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs).@*METHODS@#A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute.@*RESULTS@#Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs.@*CONCLUSION@#The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.

Effect of caloric restriction on myocardial ischemia/reperfusion injury in mice and its mechanism / 中国生物制品学杂志

@#Objective To investigate the effect of caloric restriction(CR)on myocardial ischemia/reperfusion injury(MI/RI)in mice and its mechanism.Methods C57 mice were randomly divided into normal diet group(AL group,free feeding)and CR group(diet decreased by 10% every 2 weeks)for 8 weeks and monitored for weight changes.Each group was divided into sham operation group and MI/RI group,total 4 groups,AL + Sham group,AL + I/R group,CR + Sham group and CR + I/R group).The left anterior descending coronary artery was ligated for 30 minutes and then reperfused for 24 hours in mice of MI/RI group and mice in Sham group were only threaded but not ligated.The mice were determined for myocardial ischemia and infarct size by Evans blue/TTC staining,observed for the pathology of myocardium by HE staining,determined for the activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD)and the contents of creatine kinase-MB(CK-MB)and malondialdehvde(MDA)in myocardium by the corresponding kits,determined for serum levels of IL-1β and IL-18 by ELISA and detected for the expression of pyroptosis-associated proteins in myocardium by Western blot.Results After 8weeks,the weights of mice in CR group[(24.54 ± 0.41)g]were significantly lower than those in AL group[(31.46 ±0.25)g](t = 14.34,P<0.05).Compared with those in AL + I/R group,the area of myocardial ischemia in CR + I/R group showed no significant difference(t = 0.783 0,P>0.05),while the area of myocardial infarction decreased significantly(t = 7.250,P<0.01);The myocardial arrangement was relatively neat,and the degree of pathological changes was obviously reduced;LDH activity,CK-MB and MDA contents decreased significantly(t = 4.331,2.875 and 5.343 respectively,each P<0.05),while SOD activity increased significantly(t = 4.211,P<0.05);Serum levels of IL-1β and IL-18 decreased significantly(t = 3.375 and 4.266 respectively,each P<0.05);The expression levels of nod-like receptor protein 3(NLRP3),gasdermin D(GSDMD),apoptosis-associated speckle-like protein(ASC)and caspase-1 significantly decreased(t = 3.412,3.420,3.480 and 2.585 respectively,each P<0.05).Conclusion CR alleviated MI/RI in mice,and its mechanism was related to the inhibition of cardiac pyroptosis.

Feasibility of endoscopic submucosal dissection for the treatment of large hiatal hernia combined with refractory gastroesophageal reflux disease (with video) / 中华消化内镜杂志

Objective:To study the safety and efficacy of hiatal hernia-endoscopic submucosal dissection (HH-ESD) for the treatment of giant hiatal hernia (>3 cm in length) complicated with refractory gastroesophageal reflux disease (GERD).Methods:Patients with giant hiatal hernia complicated with refractory GERD who voluntarily received HH-ESD at the Digestive Endoscopy Center of the Affiliated People's Hospital of Inner Mongolia Medical University from April 2018 to March 2020 were included in the clinical study. The completion of HH-ESD and the occurrence of complications were observed, and the changes of indicators before and after the treatment were observed, including gastroesophageal reflux disease-health related quality of life (GERD-HRQL) score, gastroesophageal reflux disease questionnaire (GERD-Q) score, endoscopy results, 24 h esophageal pH monitoring results, esophageal high-resolution manometry results and proton pump inhibitor (PPI) usage.Results:Data of 10 patients were collected during the study, with a medical history of 2-10 years. All patients successfully underwent HH-ESD treatment. No adverse events such as perforation and massive bleeding occurred during the operation, and the hospital stay was 6-12 days. Dysphagia occurred in 3 cases after the operation, which was relieved spontaneously within 3 or 6 months. The preoperative GERD-HRQL scores ranged from 19 to 29, which were reduced to 0-14 and 0-8 at 3 and 12 months after the operation, respectively. The preoperative GERD-Q score was 9-17, and the scores at 3 and 12 months after the operation were all 6-9, which were significantly lower than those before. Gastroscopy showed that esophagitis was improved in all patients, hernia sac was reduced, and Hill grade was reduced compared with that before. The preoperative DeMeester score was 30.3-247.1, and the postoperative 12-month score was 0.2-29.9, which was significantly lower than that before. The long diameter of hiatal hernia was 3.0-6.0 cm before the operation and 0-5.0 cm at 12 months after, which was smaller than that before. At 12 months of the follow-up, 7 patients had stopped PPI, and the remaining 3 had changed to intermittent oral PPI.Conclusion:Preliminary results show that HH-ESD is safe and effective for the treatment of giant hiatal hernia complicated with refractory GERD.

Preparation of tanshinone Ⅱ_A-glycyrrhetinic acid solid lipid nanoparticles and its inhibitory effect on acne / 中国中药杂志

The optimal prescription of tanshinone Ⅱ_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.

Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid / 中国中药杂志

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

Clinicopathological analysis of 105 patients with fibrous dysplasia of cranio-maxillofacial region / 北京大学学报(医学版)

OBJECTIVE@#To compare the clinicopathologic features and prognosis of the different types of fibrous dysplasia (FD) of cranio-maxillofacial region, so as to provide a new reference for clinicians to treat these patients and make prognostic judgement.@*METHODS@#Clinical records, radiographic data and pathological information of 105 patients diagnosed with FD or McCune-Albright syndrome (MAS) at the Department of Oral Pathology, Peking University Hospital of Stomatology from January 2013 to December 2020 were collected. The patients were divided into 4 groups: monostotic FDs, polyostotic FDs, MAS and a specific type called craniofacial fibrous dysplasia (CFD) limited in the craniofacial region. The clinicopathological characteristics, treatment and follow-up data of each type were analyzed.@*RESULTS@#Of all the 105 patients, 46 were males and 59 were females, with a male-to-female ratio of 1 ∶1.3. The onset age ranged from 0 to 56 years and the median age was 12 years. On the basis of different involvement conditions, 4 types were divided. The most common type was monostotic FDs (43 cases, 40.95%), including maxilla (29 cases), mandibular (12 cases) and zygoma (2 cases). 32 cases (30.48%) were diagnosed with polyostotic FDs, 7 cases (6.67%) were MAS, and 23 cases (21.90%) were CFDs confirmed by computed tomography (CT) analysis. CFD was clearly distinct from other types of FD, such as the patient gender and the serum alkaline phosphatase level in peripheral blood before operative surgery. The pathologic findings of various types FD were quite similar, whilst the predominant fibrous tissue hyperplasia could be observed in polyostotic FDs and MAS types.@*CONCLUSION@#The clinicopathologic features of FD in the cranio-maxillofacial region are different from the FD lesions in other parts of the body. The clinicopathological features of CFD are significantly different from those of monostotic and polyostotic FDs in the cranio-maxillofacial region. Therefore, the clinicians should pay attention to distinguish CFD in clinic, imaging and pathology aspects, so as to further clarify its features in clinic management and prognosis.

Mechanism of IGF-1 in Pathological Pain / 中国生物化学与分子生物学报

Pathological pain is also called chronic pain, including neuropathic pain, inflammatory pain, and cancer pain. These three types of pain mainly come from complications or late effects of various diseases. Pathological pain is a kind of sensation, different from visual, auditory and other independent existence, but mixed with other sensations. It is difficult to distinguish accurately, which brings great difficulties to clinical treatment and patient recovery. Although the search for analgesic targets has been extensively and deeply studied in pain-related fields, there is still a lack of effective therapies or drugs with less or no side effects. Insulin-like growth factor-1 (IGF-1) is a member of the insulin-like growth factor family, which is widely expressed in the central nervous system and peripheral nervous system and exerts neurotrophic and nerve repair effects, and has received increasing attention in the field of pain in recent years. However, in the study of pathological pain, some scholars have found that IGF-1 plays two opposite roles of neuroprotection and neurotoxicity in the occurrence and maintenance of neuropathic pain and inflammatory pain, which can not only promote the transmission of nociceptive information but also block the transmission of nociceptive information. In cancer pain, it is found that IGF-1 only participates in the transmission of nociceptive signals and then plays a neurotoxic role. This paper briefly reviews the mechanism of IGF-1 participation in three kinds of pathological pain, and discusses the possibility of IGF-1 as an analgesic target.

Circular RNA PVT1 Promotes Proliferation and Represses Apoptosis of Colorectal Cancer Cells / 中国生物化学与分子生物学报

Circular RNAs (circRNAs) are a novel class of long-chain non-coding RNAs. Preceding evidence has showed that circRNAs participate in the development and progression of various tumors. In the present study, we investigated the expression of circRNAs in 5 paired colorectal cancer (CRC) tissues and adjacent normal tissues with circRNA high-throughput sequencing. Totally 477 differentially expressed circRNAs were identified between CRC tissues and non-cancerous matched tissues, which included 252 significantly overexpressed circRNAs and 225 downregulated circRNAs. CircRNA plasmacytoma variant translocation 1 (circPVT1), the most up-regulated expression circRNA, was further confirmed by qRT-PCR in 150 colorectal cancer tissues and matched normal mucosae. Our data revealed that circPVT1 showed a significant up-regulation trend in CRC tissues compared with matched normal mucosae. Similarly, compared with normal colorectal mucosa cells, the expression of circPVT1 in colorectal cancer cell lines was significantly up-regulated (P<0. 05). Functionally, silence with siRNA or overexpression of circPVT1 in colorectal cancer cells was applied to determine the biological functions of circPVT1, including cell proliferation, apoptosis, and cell cycle, etc. The results show that circPVT1 expression significantly attenuated apoptosis, induced replication and promoted proliferation of colorectal cancer cells in vitro. In summary, our findings indicate that circPVT1 plays an oncogenic role in CRC and might be a potential novel target for CRC therapy.

Effects of HDAC4 on IL-1β-induced matrix metalloproteinase expression regulated partially through the WNT3A/β-catenin pathway / 中华医学杂志(英文版)

BACKGROUND@#Histone deacetylase 4 (HDAC4) regulates chondrocyte hypertrophy and bone formation. The aim of the present study was to explore the effects of HDAC4 on Interleukin 1 beta (IL-1β)-induced chondrocyte extracellular matrix degradation and whether it is regulated through the WNT family member 3A (WNT3A)/β-catenin signaling pathway.@*METHODS@#Primary chondrocytes (CC) and human chondrosarcoma cells (SW1353 cells) were treated with IL-1β and the level of HDAC4 was assayed using Western blotting. Then, HDAC4 expression in the SW1353 cells was silenced using small interfering RNA to detect the effect of HDAC4 knockdown on the levels of matrix metalloproteinase 3 (MMP3) and MMP13 induced by IL-1β. After transfection with HDAC4 plasmids, the overexpression efficiency was examined using Real-time quantitative polymerase chain reaction (qRT-PCR) and the levels of MMP3 and MMP13 were assayed using Western blotting. After incubation with IL-1β, the translocation of β-catenin into the nucleus was observed using immunofluorescence staining in SW1353 cells to investigate the activation of the WNT3A/β-catenin signaling pathway. Finally, treatment with WNT3A and transfection with glycogen synthase kinase 3 beta (GSK3β) plasmids were assessed for their effects on HDAC4 levels using Western blotting.@*RESULTS@#IL-1β downregulated HDAC4 levels in chondrocytes and SW1353 cells. Furthermore, HDAC4 knockdown increased the levels of MMP3 and MMP13, which contributed to the degradation of the extracellular matrix. Overexpression of HDAC4 inhibited IL-1β-induced increases in MMP3 and MMP13. IL-1β upregulated the levels of WNT3A, and WNT3A reduced HDAC4 levels in SW1353 cells. GSK-3β rescued IL-1β-induced downregulation of HDAC4 in SW1353 cells.@*CONCLUSION@#HDAC4 exerted an inhibitory effect on IL-1β-induced extracellular matrix degradation and was regulated partially by the WNT3A/β-catenin signaling pathway.

The Prognostic Value of Early Relapse after Autologous Hematopoietic Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To assess the impact of early relapse (ER) after autologous hematopoietic stem cell transplan-tation (AHSCT) on overall survival (OS) for multiple myeloma (MM) patients.@*METHODS@#Clinical data of 37 patients with MM undergoing AHSCT in department of hematology of Shanxi Bethune Hospital from January 2012 to December 2017 were retrospectively analyzed. The effect of ER on OS of patients was analyzed. The effects of international staging system (ISS) staging, cytogenetics, pre-transplant efficacy, minimal residual disease, and age on OS of the patients were also analyzed respectively.@*RESULTS@#Among the 37 patients, 13 cases (35.1%) had ER, and 24 cases (64.9%) had non-ER. 3 patients with ER had extramedullary disease, but none with non-ER showed extramedullary disease. More than or equal to very good partial rate (VGPR) in patients with ER and without ER were 3 cases (23.1%) and 15 cases (62.5%), respectively, and the curative effect of the former was significantly lower than that of the latter (P<0.05). The median follow-up time was 31 (12-96) months, and median OS time was 93 months in all the patients. The median survival time of patients with ER was 17 months, and the median progression free survival was 7 months, both were significantly shorter than 93 months and 38 months of patients with non-ER (P<0.05). Univariate analysis showed that the OS was affected by ER, cytogenetic abnormalities (FISH), and ≥VGPR before transplantation. Multivariate analysis showed that ER was an independent prognostic factor.@*CONCLUSION@#The prognosis of patients with ER after AHSCT in newly diagnosed MM is poor. ER is an independent prognostic factor of survival.

Protective Effect of Tongluo Shenggu Capsule on Function Damage of Human Umbilical Vein Endothelial Cells Induced by Glucocorticoid / 中国实验方剂学杂志

Objective:To observe the effect of Tongluo Shenggu capsule （TLSGC） on glucocorticoid-induced vascular endothelial cell functional damage， and to preliminally explore the mechanism of action through MEK-ERK signaling pathway. Method:The blood vessel of aorta rings of normal SD rats were induced <italic>in vitro</italic> intervention with methylprednisolone sodium succinate （MPS， 0.04 g·L^-1） and/or vascular endothelial growth factor （VEGF， 20 μg·L^-1）， and were treated with TLSGC（12.5， 25， 50 μg·L^-1） continuously for 5 days to observe the number， length and area of microvascular ring buds．In addition， human umbilical vein endothelial cells （HUVEC） induced by VEGF（20 μg·L^-1） were added into MPS（0.04 g·L^-1） and TLSGC （12.5， 25， 50 μg·L^-1） were added. Then， Transwell migration， Transwell invasion and lumen formation experiments were used to detect the migration， invasion and lumen formation ability of HUVEC， respectively. The content of nitric oxide（NO） in the cell supernatant was detected by nitrate reductase method， the content of endothelin 1（ET-1） in the cell supernatant was detected by dry powder method. Moreover， the protein contents of vascular endothelial growth factor receptor 2 （VEGFR2）， extracellular signal-regulated kinase （ERK）， phospho-extracellular signal-regulated kinase （p-ERK）， mitogen extracellular kinase1（MEK） and phosphorylated mitogen extracellular kinase1（p-MEK） in the cells were determined by Western blot. Result:Compared with the normal group， MPS could significantly inhibit the number， length and area of VEGF-induced rat thoracic aortic ring microvessels， HUVEC cell migration， invasion and lumen formation ability. It could reduce NO content and increase ET-1 content. MPS could also significantly reduce the protein content of VEGF-induced VEGFR2， p-MEK and p-ERK in HUVEC（<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， TLSGC could dose-dependently increase the number， length and area of MPS-induced abnormally reduced rat thoracic aortic ring microvessels， promote MPS-induced abnormally decreased HUVEC cell migration， invasion and lumen formation ability. It could increase the protein contents of NO， VEGFR2， p-MEK and p-ERK in HUVEC， and reduce abnormally increased ET-1 content（<italic>P</italic><0.05<italic>，P</italic><0.01）. Conclusion:TLSGC has a protective effect on the damage of angiogenesis and secretion of vascular endothelial cells induced by glucocorticoid， and the mechanism may be related to the activation of MEK/ERK signaling pathway.

Effect of Panlongqi Tablet on Cervical Spondylosis of Vertebral Artery Type in Rats / 中国实验方剂学杂志

Objective:To establish a model of cervical spondylosis of vertebral artery type （CSA） in rats by mixed modeling method， and observe the intervention effect of Panlongqi tablet （PLQT） on CSA rats. Method:SD rats were divided into a normal control group， a model group， low- （0.16 g·kg^-1）， medium- （0.32 g·kg^-1）， and high-dose （0.64 g·kg^-1） PLQT groups， and a Jingfukang granule （JFK， 1.35 g·kg^-1） group. The rats were treated correspondingly 24 hours after modeling for eight weeks， and those in the normal control group received an equal volume of normal saline by gavage. The limb movement was tested by the inclined plate assay， vertebral artery flow volume by multi-mode high-frequency sound wave for small animals， and microcirculatory blood flow in the pia mater by the laser Doppler. The imaging of the cervical spine was recorded and scored by X-ray micro-computed tomography （Micro CT）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of endothelin-1 （ET-1）， nitric oxide （NO）， tissue plasminogen activator （t-PA）， and plasminogen activator inhibitor （PAI）. Result:Compared with the normal control group， the model group showed decreased limb movement， vertebral artery flow volume， and microcirculatory blood flow in the pia mater， and increased imaging of the cervical spine and score （<italic>P</italic><0.05，<italic>P</italic><0.01）. PLQT could dose-dependently improve the motor function， increase the vertebral artery flow volume and microcirculatory blood flow in the pia mater， and reduce the degree and score of imaging of the cervical spine in CSA rats（<italic>P</italic><0.05，<italic>P</italic><0.01）. The serum levels of NO and t-PA were decreased and those of ET-1 and PAI were increased in the model group as compared with those in the normal control group， while such changes were reversed by PLQT treatment（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:PLQT can enhance the limb movement， promote the vertebral artery flow volume and microcirculatory blood flow in the pia mater， improve the degree of imaging of the cervical spine， regulate the vasomotor function， and improve the coagulation and fibrinolysis system of CSA rats， which shows good potential for the treatment of CSA.

Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β1 of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca2+/NFAT Signaling Pathway / 中国实验方剂学杂志

Objective:This studu aims to investigate the effect of aqueous extract of modified Xiao Xianxiongtang on the epithelial mesenchymal transition（EMT） and the change of its invasion and migration ability of human gastric cancer MGC-803 cells mediated by transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁），and to explore the mechanism of regulating Wnt5a/Ca²⁺/ activated T-cell nuclear factor（NFAT） signaling pathway to inhibit EMT and invasion and metastasis of MGC-803 cells. Method:TGF-<italic>β</italic>₁（10 μg·L^-1）was used to induce EMT and the invasion and metastasis model of human gastric cancer MGC-803 cells. Transwell chamber experiment， scratchhealing experiment， Western blot and immunofluorescence assay were used to detect cell invasion and migration ability， expression of EMT marker protein and key protein expression of Wnt5a/Ca²⁺/NFAT signaling pathway， and intracellular Ca²⁺ concentration. Result:Compared with the blank group， TGF-<italic>β</italic>₁ could significantly enhance the invasion and migration ability of MGC-803 cells（<italic>P</italic><0.01）， down-regulate the level of E-cadherin（<italic>P</italic><0.01）， up-regulate protein expressions of N-cadherin， Snail and Vimentin（<italic>P</italic><0.01）， and induce cell Wnt5a， calcineurin （CaN）， total protein of activated T-cell nuclear factor 1（NFAT1）， up-regulation of phosphorylated proteins p-NFAT1 and NFAT1 nucleoprotein and intracellular accumulation of Ca²⁺（<italic>P</italic><0.01）. Compared with the TGF-<italic>β</italic>₁ group， modified Xiao Xianxiongtang （10， 20， 40 mg·L^-1） could significantly inhibit this phenomenon，and 40 mg·L^-1 had the best effect（<italic>P</italic><0.05，<italic>P</italic><0.01）.The specific inhibitors of Wnt5a/Ca²⁺/NFAT signaling pathway （<italic>R</italic>）-（+）-Bay-K-8644 and modified Xiao Xianxiongtang （40 mg·L^-1） could significantly inhibit theinvasion and migration of MGC-803 cells mediated by TGF-<italic>β</italic>₁， up-regulate the level of E-cadherin， and down-regulate expressions of N-cadherin， Snail， Vimentin， Wnt5a， CaN and NFAT1 proteins and reduce the intracellular accumulation of Ca²⁺（<italic>P</italic><0.05，<italic>P</italic><0.01）.Moreover， （<italic>R</italic>）-（+）-Bay-K-8644 combined with modified Xiao Xianxiongtang （40 mg·L^-1） had stronger inhibitory effect（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:These results suggest that modified Xiao Xianxiongtang can inhibit the EMT mediated by TGF-<italic>β</italic>₁ via Wnt5a/Ca²⁺/NFAT signaling pathway，thereby reducing the invasion and migration ability of MGC-803 cells.

Anti-anaphylactic potential of benzoylpaeoniflorin through inhibiting HDC and MAPKs from Paeonia lactiflora / 中国天然药物

Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides (1-18) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1, 5, 6, 11, 12, 15, and 17 significantly reduced the release rate of β-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin (5) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin (5) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin (5) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin (5), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin (5) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.

The organization, regulation, and biological functions of the synaptonemal complex / 亚洲男科学杂志(英文版)

The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes. The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation, ensuring accurate meiotic chromosome segregation. Recent studies in different organisms, facilitated by advances in super-resolution microscopy, have provided insights into the macromolecular structure of the SC, including the internal organization of the meiotic chromosome axis and SC central region, the regulatory pathways that control SC assembly and dynamics, and the biological functions exerted by the SC and its substructures. This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.

Clinical Application of Screening Cell Combination Method in the Prediction of Red Blood Cell Alloantibody / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical application of screening cell combination method in the prediction of red blood cell alloantibody, so as to provide basis for clinical diagnosis.@*METHODS@#From October 2018 to April 2020, 9 680 samples were screened with automatic blood group instrument, 79 patients with positive alloantibodies were identified by 4 sets of screening cells from different manufacturers (referred to as combined method). At the same time, cell panel Panocell-16 was used for comparative analysis. Meanwhile, the combined method was also used to identify the antibodies of 20 samples from National Center for Clinical Laboratories external quality assessment (EQA) in China and 12 samples from WHO EQA.@*RESULTS@#The 79 alloantibodies included anti-Mia antibody (7 cases), anti-M antibody (13 cases), anti-Le@*CONCLUSION@#The combined method can identify the alloantibodies of red blood cells in Chinese population. The screening cells can be used for screening of irregular antibodies without wasting reagents at the same time.

Progress and prospect of machine learning in research of acupuncture and moxibustion / 中国针灸

The application progress of machine learning in research of acupuncture and moxibustion was reviewed from three aspects: mining of acupuncture and moxibustion prescription and indications, acupuncture efficacy prediction and its influencing factors, acupoint specificity and acupuncture manipulation research, and the existing problems in current research and future research trends were discussed. It is believed that the appropriate machine learning algorithm should be selected to build the model according to the research purpose and data characteristics in the future research; attention should be paid to feature design, feature selection and feature cleaning; sample data collection should be a priority, and data sharing platform and standardized data collection should be developed to improve the data quality.

Analgesic Effect of Panlongqi Tablet on Rats with Chronic Inflammatory Pain / 中国实验方剂学杂志

Objective:To observe the analgesic effect of Panlongqi tablet（PLQT） on rats with chronic inflammatory pain， and to explore mechanism of the action preliminarily from the perspective of the nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB）and mitogen-activated protein kinase（MAPKs） signaling pathways. Method:Rats were induced to establish model of chronic inflammatory pain by complete Freund adjuvant（CFA）， which was divided into normal group， model group， the PLQT 0.16，0.32，0.64 g·kg-1 group， and the ibuprofen 0.05 g·kg-1 group（also positive group）， give the medicine once a day by gavage. Standard Von Frey fiber was used to evaluated the mechanical pain threshold， acetone was used to stimulated rats inflammatory foot to get the cold-induced response score， with the mechanical pain threshold and cold-induced response score to be observed at 1， 2， 3， 4 and 6 h before and after administration on day 1， and at 4 h after administration on day 3-7. The content of PGE2， IL-1， TNF-α in serum， inflammatory foot and 4-5 lumbar spinal cord was detected by enzyme-linked immunosorbent assay（ELISA）. The protein level of MAPKs （p-p38， p-ERK， p-JNK） in lumbar spinal cord 4-5 was detected by Western blot. The expression of NF-κB p65 in the lumbar spinal cord was detected by IFA. Result:Model group had lower mechanical pain threshold and higher cold-induced response score than these in normal group（P<0.01）， while the mechanical pain threshold and cold-induce response score of the model rats were dose-dependent better regulated after administration of PLQT 0.16， 0.32， 0.64 g·kg-1·d-1（P<0.05，P<0.01）， these effect lasted 6 h， of which PLQT groups get the most significant effect on 4 h， however the effect of IBP was similar to that of PLQT medium dose group. In addition， PLQT reduced the abnormal increase of PGE2， IL-1 and TNF-α contents in serum， inflammatory foot and spinal cord of rats in model group， decreased the protein phosphorylation levels of ERK and JNK in spinal cord， and decreased the protein expression of NF-κB p65， that was significant in the PLQT high-dose group（P<0.01）. Conclusion:PLQT had significant analgesic effect on chronic inflammatory pain model rats， which may be related to the inhibition of NF-κB and MAPKs signaling pathways in spinal cord.

Research Progress on Antitumor Active Components and Mechanism of Xiao Xianxiongtang / 中国实验方剂学杂志

Tumor is one of the diseases that seriously endanger human health， and how to treat tumor effectively is still one of the important problems in the field of medicine. At present， most of the radiotherapies and chemical drugs for cancer have serious side effect despite of an obvious efficacy. With a unique syndrome differentiation treatment system and overall concept， traditional Chinese medicine has become the key research and development object of antitumor drugs due to many advantages， such as multiple channels， multiple levels， multiple links， multiple targets and less toxicity， and could can fully mobilize the immune and epidemic prevention mechanism of the body. A large number of studies have shown that Xiao Xianxiongtang and its effective ingredients have obvious antitumor effect. Many doctors have applied Xiao Xianxiongtang and modified formulas in clinical treatment of tumors， and relevant pharmacological studies have also confirmed the effectiveness of this formula， but with a lack of systematic summary of its effective ingredients and its mechanism of action. Now， with alkaloids， ketones， sterols and phenols in Xiao Xianxiongtang as the starting point， this study mainly focuses on inhibition of tumor cell proliferation， invasion and migration， induction of tumor cell apoptosis and autophagy， inhibition of tumor cell cycle， enhancement of tumor cell sensitivity， inhibition of tumor angiogenesis and regulation of immunosuppressive tumor microenvironment from two ways to sort out composition， function and mechanism of drugs. In this paper， effective components， main targets and mechanism of intervention in the tumor development of Xiao Xianxiongtang were reviewed， in order to provide a new idea for subsequent antitumor research and development of this prescription.

Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV / 中华心血管病杂志

Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease （CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74 (0.34, 0.94)×109/L vs. 0.99 (0.71, 1.29)×109/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20) μg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m2 vs. 22.0 (20.0, 24.0) kg/m2，P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25.0 kg/m2, which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors （all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.