Earthworm Protein Protects Vascular Endothelial Function in Spontaneously Hypertensive Rats via PI3K/Akt/Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E2-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10-3 g·kg-1·d-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg-1·d-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe2+）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

The characteristics and influencing factors of medicine cost for orthopedic surgery patients in hospitals of Shanxi province / 中国药房

OBJECTIVE To analyze the characteristics and influencing factors of medicine cost for orthopedic surgery patients in Shanxi province， and to provide reference for the rational management of medicine cost in orthopedic surgery patients. METHODS A retrospective analysis was conducted on the case information of 584 204 orthopedic surgery patients in Shanxi province from 2016 to 2021. Medicine cost was analyzed by year， region， hospital level， type of surgery and type of surgical incision. Single factor analysis and generalized linear regression model were used to analyze the influencing factors of total medicine cost， and structural equation model was used for verification. RESULTS The research findings indicated that joint replacement surgery （42.61%） and post-fracture external fixation surgery （12.60%） were the most common types of procedures. There was statistical significance in medicine cost for different surgical types among different regions and hospital levels （P＜0.05）. In the Jinzhong region， the total medicine cost for post-fracture external fixation surgery was the highest （[ 11 719.97±4 374.73） yuan]， while in tertiary grade A hospitals， the total medicine cost for post-fracture external fixation surgery was also the highest （[ 13 584.71±4 531.82） yuan]. Among class Ⅰ incision surgeries， the cost of antibiotics for post-fracture external fixation surgery was the highest （[ 1 176.25±341.42） yuan]. Generalized linear regression model revealed that hospital location， hospital level， gender， payment method， length of hospital stays， and surgical type were the independent influencing factors for total medicine cost （P＜0.05）. Structural equation model further disclosed that hospital level， payment type， and surgical type had significant effects on total medicine cost （P＜0.05）. CONCLUSIONS Attention should be paid to the high cost of antibiotics for class Ⅰ incision surgery， and further research on their rational use should be conducted.

Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease / 中国药房

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Identification and expression analysis of TCP family members in tobacco (Nicotiana tabacum L.) / 生物工程学报

TCP family as plant specific transcription factor, plays an important role in different aspects of plant development. In order to screen TCP family members in tobacco, the homologous sequences of tobacco and Arabidopsis TCP family were identified by genome-wide homologous alignment. The physicochemical properties, phylogenetic relationships and cis-acting elements were analyzed by bioinformatics. The homologous genes of AtTCP3/AtTCP4 were screened, and RT-qPCR was used to detect the changes of gene expression upon 20% PEG6000 treatment. The results show that tobacco contains 63 TCP family members. Their amino acid sequence length ranged from 89 aa to 596 aa, and their protein hydropathicity grand average of hydropathicity (GRAVY) ranged from -1.147 to 0.125. The isoelectric point (pI) ranges from 4.42 to 9.94, the number of introns is 0 to 3, and the subcellular location is all located in the nucleus. The results of conserved domain and phylogenetic relationship analysis showed that the tobacco TCP family can be divided into PCF, CIN and CYC/TB1 subfamilies, and each subfamily has a stable sequence. The results of cis-acting elements in gene promoter region showed that TCP family genes contain low docile acting elements (LTR) and a variety of stress and metabolic regulation related elements (MYB, MYC). Analysis of gene expression patterns showed that AtTCP3/AtTCP4 homologous genes (NtTCP6, NtTCP28, NtTCP30, NtTCP33, NtTCP42, NtTCP57, NtTCP63) accounted for 20% PEG6000 treatment significantly up-regulated/down-regulated expression, and NtTCP30 and NtTCP57 genes were selected as candidate genes in response to drought. The results of this study analyzed the TCP family in the tobacco genome and provided candidate genes for the study of drought-resistance gene function and variety breeding in tobacco.

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.

The proportion of Th17 cells in patients with systemic sclerosis: a Meta-analysis / 中华风湿病学杂志

Objective:To clarify peripheral Th17 level in SSc patients and its correlation with disease.Methods:Chinese databases CNKI, CBM, Wanfang and VIP, and English databases PubMed, EMBASE, Web of Science, Cochrane Library and Science Direct were searched to collect a case-control study on the content of Th17 cells in peripheral blood of patients with SSc. The papers published when the database was first developed in 25 February 2021. Meta-analysis was conducted using Stata 12.0 software, and I2 and Egger tests were used to evaluate the heterogeneity and publication bias between studies. Results:A total of 26 case-controls were included in the study, including 1 160 patients with SSc and 778 healthy controls. Overall, the percentage of Th17 cells in SSc patients was higher than in healthy controls [SMD(95% CI)=1.85 (1.33, 2.38), P<0.001], which was most significant in IL-17 +Th17 concentration [SMD(95% CI)=1.88 (1.28, 2.48), P<0.001]. As for disease activity, the proportion of Th17 cells in active SSc patients was much higher than those of patients in remission [SMD(95% CI)=1.92 (1.12, 2.71), P<0.001]. SSc patients had a reduced Th17 level after receiving DMARDs treatment [SMD(95% CI)=-0.74 (-1.05, -0.42), P=0.029]. Conclusion:The number of Th17 cells increase significantly in the peripheral blood of patients with SSc, and is related to disease activity. DMARDs can be used to treat this disease by downregulating Th17 levels.

Clinical characteristics and risk factors for severe disease of hemorrhagic fever with renal syndrome in underage patients / 中华传染病杂志

Objective:To analyze the clinical characteristics and risk factors for severe disease of hemorrhagic fever with renal syndrome (HFRS) in underage patients, and to construct the severe disease risk model.Methods:A total of 170 HFRS patients (<18 years old) from the Second Affiliated Hospital of Air Force Medical University (153 cases) and the Second Affiliated Hospital of Xi′an Jiaotong University (17 cases) from January 2009 to December 2021 were included. According to the severity of the disease, the patients were divided into mild and severe groups. Baseline demographic data, symptoms, signs, laboratory examination on admission and prognosis were analyzed between the two groups. Statistical comparisons were performed using the Mann-Whitney U test and chi-square test.Binary logistic regression was used to analyze the independent risk factors of patients with severe disease, and the severe disease risk model was built.The receiver operator characteristic curve was used to analyze the value of the risk model in predicting severity of disease. Results:Among the 170 underage patients, 132 (77.6%) were males, aged (14.9±3.1) years, including 124 cases in mild group and 46 cases in severe group. One hundred and sixty-nine cases (99.4%) had fever, 119 cases (70.0%) had headache, 106 cases (62.4%) had lumbago, 158 cases (92.9%) had skin and mucous congestion, and 101 cases (59.4%) had nausea and vomiting. Renal percussive pain was found in 139(81.8%) patients. The incidence of nausea and vomiting and bleeding of skin and mucosa in the severe group were 71.7%(33/46) and 67.4%(31/46), respectively, which were both higher than those in the mild group (54.8%(68/124) and 44.4%(55/124), respectively), and the differences were statistically significant ( χ2=3.97 and 7.12, respectively, both P<0.05). There were significant differences in platelet count, activated partial thromboplastin time (APTT), serum creatinine (SCr), aspartate aminotransferase, alanine aminotransferase, leukocyte count, total bilirubin and albumin levels between the two groups ( Z=-4.14, -4.04, -4.87, -3.90, -4.07, -2.60, -2.78 and t=2.50, respectively, all P<0.05). Binary logistic regression analysis showed that chemosis (odds ratio ( OR)=8.035, 95% confidence interval (95% CI) 2.946 to 21.916), SCr ( OR=1.010, 95% CI 1.006 to 1.015) and APTT ( OR=1.049, 95% CI 1.003 to 1.098) were the independent risk factors for severe HFRS in the underage patients. The risk model was constructed as: Logit(P)=-10.323+ 2.084×chemosis (no=0, grade Ⅰ=1, grade Ⅱ=2, grade Ⅲ=3)+ 0.010×SCr (μmol/L)+ 0.048×APTT (s). The area under the curve to predict severity of disease in underage HFRS patients was 0.868, with an optimal cut-off value of -4.39, with a sensitivity of 73.90% and a specificity of 91.10%. According to the internal verification of the data of the study based on the severe disease risk model, 34 out of 46 patients with severe disease were severe (sensitivity, 73.91%), 113 out of 124 patients with mild disease were mild (specificity, 91.13%). Conclusions:The clinical manifestations of the underage HFRS patients are not typical.The main manifestations are fever, headache and lumbago, nausea and vomiting, and the incidences of skin and mucous congestion and renal percussive pain are high.Chemosis, SCr and APTT are independent risk factors for severe disease in underage patients with HFRS. The severe disease risk model could effectively predict the severity of disease.

Effect of acute sleep fragmentation on cognitive function and hippocampal Homer1a expression in aged rats / 中华行为医学与脑科学杂志

Objective:To explore the effects of acute sleep fragmentation (SF) on cognitive function and the relationship between hippocampal Homer1a and synaptic plasticity in aged rats.Methods:One hundred and eight SPF grade male SD rats aged 22 to 24 months were divided into three groups according to random number table: control group (Control group), non-sleep fragmentation group (NSF group) and sleep fragmentation group (SF group), with 36 rats in each group.A sleep fragmentation model was established by sleep deprivation rod method.Morris water maze and novel object recognition tests were used to evaluate the learning and memory function of rats.Homer1a expression in hippocampus was detected by Western blot, and its distribution in CA1 area of hippocampus was observed by immunohistochemical staining.Golgi staining was used to observe the density of dendritic spines in CA1 area of hippocampus, and in vitro electrophysiological patch clamp test was used to detect the slope of field excitatory postsynaptic potential(fEPSP) from CA3 to CA1 in hippocampus.SPSS 22.0 and GraphPad Prism 9.3 softwares were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-Kramer test was used for further pairwise comparison. Results:(1)In the behavioral tests, there were statistical differences in the times of crossing the original platform, the target quadrant residence time and the new object recognition index at 1 h and 24 h among the three groups( F=13.63, 11.34, 21.26, 16.22, all P<0.01). The times of crossing the original platform in SF group((2.00±1.27) times) was lower than that of Control group ((5.67±2.16) times) and NSF group ((6.50±2.35) times) (both P<0.05). The target quadrant residence time in SF group ((9.02±4.84) s) was shorter than that in Control group ((24.73±7.37) s) and NSF group ((27.81±8.37)s) (both P<0.05). The new object recognition index at 1 h and 24 h in SF group were lower than those in Control group and NSF group (all P<0.05). (2) In Western blot assay, the expression of Homer1a protein in hippocampus of SF group(0.91±0.13) was higher than that of Control group(0.70±0.05) and NSF group(0.74±0.04)(both P<0.05). (3) In immunohistochemical staining, the optical density value of the Homer1a protein in CA1 area of hippocampus in the SF group was higher than that in the Control group and NSF group(both P<0.05). (4) In Golgi staining, the density of dendritic spines in CA1 area of hippocampus in SF group was lower than that in Control group and NSF group (both P<0.05). (5) In vitro electrophysiological test showed that the slope of fEPSP in CA3-CA1 area of hippocampus in SF group were lower than that in Control group and NSF group (both P<0.05). Conclusion:Acute SF intervention in aged rats can cause cognitive impairment, which may be associated with the inhibition of hippocampal synaptic plasticity induced by hippocampal Homer1a overexpression.

Overview of systematic review on TCM for functional dyspepsia / 国际中医中药杂志

Objective:To re-evaluate the reliability of the conclusions of the systematic reviews (SR)/meta-analysis (MA) of Traditional Chinese Medicine (TCM) in the treatment of functional dyspepsia (FD).Methods:CNKI, CBM, WanFang Data, VIP, PubMed, Cochrane Library, and Embase were searched from the establishment of the database to March 30, 2022. Two researchers independently screened literature and extracted data, and included SRs/MAs in the treatment of FD with TCM. The AMSTAR 2 and GRADE tools were used to evaluate the included the study carried out methodological quality evaluation, outcome evidence quality grading, and descriptive analysis of the main outcome.Results:A total of 28 SRs/MAs were included, with 34 outcome indicators. According to the AMSTAR 2 evaluation results, 21 SRs/MAs were of medium quality, and 7 SRs/MAs were of low quality. The GRADE quality of evidence grading results showed that of the 100 evidence bodies, 13 were of high quality, 58 were of moderate quality, 24 were of low quality, and 5 were of very low quality.Conclusion:TCM in the treatment of FD can improve the clinical efficiency, improve the cure rate, reduce the recurrence rate, and improve the clinical symptoms, but the methodological quality and evidence quality of related SRs/MAs have certain defects, so this conclusion should be treated with caution.

Role of Homer1a/mGluR5 signaling pathway in cognitive dysfunction induced by sleep deprivation in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of Homer1a/metabotropic glutamate receptor 5 (mGluR5) signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods:One hundred and four SPF healthy male Sprague-Dawley rats, aged 22-24 months, weighing 320-360 g, were divided into 4 groups ( n=26 each) using a random number table method: normal control group (group Control), sleep deprivation+ vehicle group (group SD+ Vehicle), sleep deprivation+ mGluR5 forward allosteric agent CDPPB group (group SD+ CDPPB), and sleep deprivation+ mGluR5 antagonist MPEP group (group SD+ MPEP). A 48-h sleep deprivation model was developed by sleep-deprived rod method. At the beginning of developing the model and 24 h after developing the model, CDPPB 10 mg/kg, MPEP 10 mg/kg and the equal volume of 1% Tween 80 were intraperitoneally injected in group SD+ CDPPB, group SD+ MPEP and group SD+ Vehicle, respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model. The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot, the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining, and the field excitatory postsynaptic potential (fEPSP) slope in the hippocampal CA1 region was detected by isolated electrophysiology. Results:Compared with Control group, the number of crossing the original platform, time of staying at the target quadrant, and novel object recognition index at 1 and 24 h after training were significantly decreased, the expression of Homer1a in the hippocampus was up-regulated, the expression of mGluR5 in the hippocampus was down-regulated, and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+ Vehicle ( P<0.05). Compared with group SD+ Vehicle, the number of crossing the original platform, time of staying at target quadrant, and novel object recognition index at 1 and 24 h after training were significantly increased, the expression of mGluR5 in hippocampus was up-regulated, and the density of dendritic spines and fEPSP slope in the hippocampal CA1 region were increased in group SD+ MPEP( P<0.05), and no statistically significant change was found in the parameters mentioned above in group SD+ CDPPB ( P>0.05). Conclusions:Sleep deprivation impairs the synaptic plasticity of hippocampal neurons by regulating Homer1a/mGluR5 signaling pathway, and thus mediating the process of cognitive dysfunction in aged rats.

Effect of sleep fragmentation on postoperative cognitive dysfunction and hippocampal glutamatergic metabolism in aged mice anesthetized with isoflurane / 中华麻醉学杂志

Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.

Relationship between BNIP3L and mitochondrial dysfunction in hippocampus of mice with sepsis-associated encephalopathy / 中华麻醉学杂志

Objective:To evaluate the relationship between B-cell lymphoma/adenovirus E1B19 kDa-interacting protein 3-like protein (BNIP3L)/adenovirus E1B-interacting protein and mitochondrial dysfunction in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:One hundred and eighty C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=45 each) using a random number table method: control group (C group), sham operation group (Sham group), SAE group, and SAE+ BNIP3L agonist carfilzomib group (SC group). The sepsis model was developed by cecal ligation and puncture (CLP) in anesthetized animals. In SC group, carfilzomib 2 mg/kg was intraperitoneally injected at 2 h after CLP. Twenty mice in each group were selected, and the survival at 7 days after operation was recorded. Eight surviving mice in each group were selected at 1 week after CLP for Morris water maze test. The remaining mice were sacrificed at 24 h after surgery, and the hippocampal tissues were harvested for determination of the expression of BNIP3L (by immunofluorescence) and BNIP3L in mitochondrial protein (by Western blot) and for microscopic examination of the morphological structure of mitochondria. The mitochondrial ATP content was measured by fluorescein-fluorescence enzyme luminescence method, and the mitochondrial membrane potential (MMP) was measured by fluorescence spectrophotometry. Results:Compared with C and Sham groups, the survival rate was significantly decreased, the escape latency was prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform region was decreased, the expression of BNIP3L in the hippocampal mitochondria was down-regulated, the MMP and content of mitochondrial ATP were decreased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was marked in SAE group. Compared with SAE group, the survival rate was significantly increased, the escape latency was shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform region was increased, the expression of BNIP3L in the hippocampal mitochondria was up-regulated, the MMP and content of mitochondrial ATP were increased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was attenuated in SC group. Conclusions:BNIP3L-mediated mitochondrial dysfunction may be involved in the mechanism of SAE developed in mice.

Interpretation of the international expert consensus guideline on exercise management for older adults / 中华老年医学杂志

Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiopulmonary fitness in older adults and may eventually lead to reduced capabilities to conduct daily activities and independent living.Exercise plays an important role in maintaining physical function and mental health, preventing and treating chronic diseases, reducing mortality, and improving the quality of life in older people.In 2021, the International Conference of Frailty and Sarcopenia Research(ICFSR)proposed international expert consensus guidelines on exercise recommendations for older people.It mainly introduces two aging phenotypes and six recommended exercise modalities and discusses the effects of exercise on maintaining physical health and preventing common chronic diseases and geriatric syndromes.It aims to provide suggestions for older adults to maintain physical fitness and prevent disease progression and disability via exercise.We intend to interpret the important contents of the guidelines to provide a reference for exercise research and practical applications in the elderly in China.

Research progress on factors influencing immobility in the elderly / 中华老年医学杂志

Immobility in older people refers to the loss of mobility, including walking, driving and using public or other forms of transport, and reflects the declining ability of older people to carry out their daily lives.The physical and psychological problems caused by immobility, such as high morbidity rates, worse quality of life and even social isolation, will present serious challenges to the health of older people.Research has shown that disease, exercise & muscle, diet & nutrition, society and other factors all contribute to the onset of immobility in older people.This review focuses on the influencing factors of immobility in older adults.

Effect of BiPAP ventilation on respiratory physiology in patients with stable COPD / 中华健康管理学杂志

Objective:To observe the physiological effect of bi-level positive airway pressure (BiPAP) ventilation among stable chronic obstructive pulmonary disease (COPD) patients.Methods:This was a small sample size, exploratory, interventional study. A total of 10 outpatients with stable COPD were included from Department of Pulmonary and Critical Care Medicine of Zhujiang Hospital, Southern Medical University between January 2018 and December 2018. The BiPAP mode of noninvasive mechanical ventilation was adopted. The inspiratory positive airway pressure was gradually increased from 10 cmH 2O (1 cmH 2O=0.098 kPa) to 24 cmH 2O, and each time by 2 cmH 2O. The expiratory positive airway pressure remained unchanged at 4 cmH 2O. Baseline and test data were collected before and during the ventilation for comparison, including total respiratory cycle time (T tot), inspiratory time (T i), inspiratory time (T e), inspiratory tidal volume (V Ti); mouth pressure (P mo), esophageal pressure (P eso), transdiaphragmatic pressure (P di), esophageal pressure time product (PTP es), diaphragm pressure time product (PTP di), root mean square of electromyography of diaphragm (RMS), V e/RMS, inspiratory capacity (IC), the change in end-expiratory lung volume (ΔEELV) and dynamic PEEPi (PEEPi dyn). Results:All the 10 patients completed the trial. Compared to calm breathing, V Ti, V e, P mo, IC, ΔEELV score and V e/RMS increased significantly with increasing pressure levels (all P<0.05); T e only increased significantly at 20-22 cmH 2O pressure levels compared to calm breathing ( P<0.05). P di, PTP es, PTP di, RMS and RMS/RMS max decreased significantly with increasing levels (all P<0.05). PTP es and PTP di converged to 0 and no longer showed significant changes after the 18 cmH 2O pressure level. RMS and RMS/RMS max flattened out at pressure level greater than 16 cmH 2O. T i/T tot only significantly decreased at the 20 cmH 2O pressure level compared to calm breathing. PEEPi dyn showed a tendency to decrease and then increase with increasing pressure levels. Conclusion:BiPAP ventilation, at appropriate pressure levels, significantly relieves pulmonary ventilation disorders and reduces the load of respiratory muscle in patients with stable COPD.

Pharmacogenetic testing improves treatment responses in patients with PLA2R-related membranous nephropathy / 南方医科大学学报

OBJECTIVE@#To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients.@*METHODS@#A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment.@*RESULTS@#Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05).@*CONCLUSION@#Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.

Anti-endothelial cell antibodies in predicting early miscarriage / 北京大学学报(医学版)

OBJECTIVE@#To explore the clinical significance of anti-endothelial cell antibodies (AECA) in predicting early miscarriage.@*METHODS@#A total of 122 pregnant women with no history of autoimmune diseases who underwent prenatal examination at Peking University People's Hospital from January 2020 to December 2022 were selected, and they were tested for AECA. Based on the history of early miscarriage (gestational age at miscarriage < 12 weeks), the participants were divided into an early miscarriage group and a control group. t-tests, non-parametric Wilcoxon tests, Chi-square tests, and Fisher's exact probability method were used to compare general information and laboratory indicators between the two groups. A multivariate Logistic regression model was used to analyze the factors associated with early miscarriage. The natural miscarriage rates were assessed through follow-up with pregnant women, and Kaplan-Meier survival analysis was employed to compare the natural miscarriage rates between AECA-positive and AECA-negative pregnant women.@*RESULTS@#(1) A total of 122 pregnant women were enrolled, comprising 35 cases (28.7%) in the early miscarriage group, with an average age of (32.1±6.1) years, and 87 cases (71.3%) in the control group, with an average age of (30.7±5.1) years. The early miscarriage group had higher gravidity [3 (2, 4) vs. 1 (1, 2), Z=-6.402, P < 0.001] and a higher prevalence of hypertension (11.4% vs.1.1%, P=0.024). The positive rate of AECA in the early miscarriage group (34.3% vs. 8.0%, χ2=13.070, P < 0.001) and the proportion of elevated immunoglobulin G (17.1% vs. 4.6%, P=0.032) were significantly higher than that in the control group. (2) Multivariate logistic regression analysis showed that higher gravidity (OR=4.149, 95%CI: 2.287-7.529, P < 0.001), AECA positivity (OR= 4.288, 95% CI: 1.157-15.893, P=0.029), and elevated immunoglobulin G levels (OR =6.177, 95%CI: 1.156-33.015, P=0.033) were risk factors for early miscarriage. (3) The 122 pregnant women were categorized into two groups: the AECA-positive group (19 cases) and the AECA-negative group (103 cases). Survival analysis demonstrated that at the end of 12 weeks of gestation, the fetal survival rate in the AECA-positive group was significantly lower than that in the AECA-negative group (84.2% vs. 96.1%, P= 0.035).@*CONCLUSION@#Higher gravidity, AECA positivity, and elevated immunoglobulin G levels are significant risk factors for early miscarriage. The results demonstrate that AECA is a novel predicting test in early miscarriage.

Thymoma complicated with polymyositis and myasthenia gravis: A case report / 中国胸心血管外科临床杂志

@#Thymoma complicated with polymyositis and myasthenia gravis is a rare case, which can be clearly diagnosed and given symptomatic treatment according to its own diagnostic criteria, imaging and laboratory examinations. This paper reports the clinical data of a thymoma patient with polymyositis and myasthenia gravis admitted to the Seventh Affiliated Hospital of Sun Yat-Sen University, and discusses the possible pathogenesis and treatment methods.

Clinical diagnosis and treatment of hereditary thrombocytopenia and purpura: a report of five cases and literature review / 中华血液学杂志

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.

Knowledge, attitudes and practices regarding tuberculosis prevention and control:analysis of influencing factors of prevention and control behavior among college students in Wuhan, China / 中国学校卫生

Objective@#To determine the knowledge, attitudes and practices (KAP) regarding tuberculosis prevention and control among college students in Wuhan, China, while analyzing the factors affecting tuberculosis prevention behavior.@*Methods@#Referring to the National KAP Questionnaire for Tuberculosis Prevention and Control among College Students, which was designed by China Center for Disease Control and Prevention, 22 colleges and universities in Wuhan were selected using a judgment sampling method, and a questionnaire survey was carried out through the online questionnaire platform. The formation of tuberculosis prevention and control behavior among this population was analyzed by single factor and multi factor Logistic regression.@*Results@#The total awareness rate of KAP regarding tuberculosis prevention and control among college students in Wuhan was 79.69%; the awareness rate of core knowledge was 79.28%, and the passing rate was 92.46%. The correct attitude holding rate was 89.69%, while the passing rate was 90.56%. In respect to correct behavior, the formation rate was 72.11%, with a passing rate of 96.62%. The multivariate Logistic regression analysis showed that the following factors were more likely to promote tuberculosis prevention and control behaviors that met the target: female college students ( OR =1.86); college students whose father had a primary school education level, junior high school and equivalent, high school and equivalent, and junior high school students ( OR =2.94, 3.05, 3.17, 3.24 ); no history of tuberculosis ( OR =3.32); the passing knowledge of core knowledge ( OR =9.91), and the passing attitude holding score ( OR =7.35)( P <0.05).@*Conclusion@#The overall awareness rate of KAP regarding tuberculosis prevention and control among college students in Wuhan is acceptable,the mainly influenced factors are gender, history of tuberculosis, awareness rate of core knowledge about prevention and control, attitudes and cognition, and parents educational background.