Therapeutic drug monitoring of linezolid and exploring optimal regimens and a toxicity-related nomogram in elderly patients: a multicentre, prospective, non-interventional study.

BACKGROUND: The concentrations of linezolid, its optimal regimen and the associated side effects in elderly patients remain unclear. METHODS: In this multicentre, prospective study, elderly patients receiving linezolid at four tertiary hospitals in Beijing between May 2021 and December 2022 were included. Linezolid concentrations and haematological toxicity were monitored dynamically. Risk factors for linezolid overexposure and moderate-to-severe linezolid-induced thrombocytopenia (M/S LIT) were analysed, and a predictive model of M/S LIT was developed. RESULTS: A total of 860 linezolid concentrations were measured in 313 patients. The median trough concentrations of linezolid were 24.4 (15.3, 35.8) mg/L at 36-72 h and 26.1 (17.0, 38.1) mg/L at 5-10 days (P = 0.132). Severe linezolid exposure was independently associated with age, estimated glomerular filtration rate (eGFR) and the worst SOFA score (SOFA1), and we further recommended dose regimens for elderly patients based on these findings. The incidences of linezolid-induced thrombocytopenia(LIT) and M/S LIT were 73.5% and 47.6%, respectively. M/S LIT was independently correlated with treatment duration, average trough concentration (TDMa), baseline platelet count, eGFR and baseline SOFA score (SOFA0). The developed nomogram predicted M/S LIT with an area under the curve of 0.767 (95% CI 0.715-0.820), a sensitivity of 71.1% and a specificity of 73.2%. CONCLUSIONS: Linezolid trough concentrations increased dramatically in the elderly, by about 10 mg/L in patients aged 65-80 years, followed by a further increase of 10 mg/L for every 10 years of age. Therapeutic drug monitoring is recommended in elderly patients receiving linezolid. The developed nomogram may predict M/S LIT and guide dosage adjustments of linezolid. Clinical trial registration number: ChiCTR2100045707.

Necessity for higher teicoplanin doses in older adults: a multicenter prospective observational study in China.

BACKGROUND: Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. METHODS: We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. RESULTS: From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8-14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. CONCLUSIONS: Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. TRIAL REGISTRATION: ChiCTR2100046811; 28/05/2021.

Antimicrobial resistance and related risk factors of carbapenem-resistant Klebsiella pneumoniae isolated from blood / 中国感染控制杂志

Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from blood and the related risk factors for infection in patients.Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae(KP)were isolated during hospitalization period in a hos-pital from January 2018 to December 2021 were retrospectively analyzed.Patients were divided into CRKP group(n=114)and non-CRKP group(n=269)based on antimicrobial resistance.According to the prognosis,114 patients in the CRKP group were subdivided into the death group(n=30)and the survival group(n=84).General informa-tion,underlying diseases,antimicrobial use,and infection outcomes of two groups of patients were compared,and risk factors for infection and death after infection were analyzed.Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends,with statistically significant differences(both P=0.008).The CRKP group had higher resistance rates to amikacin,aztreonam,compound sulfamethoxazole,ciprofloxacin,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,tigecycline,ceftazidime,tobramycin,and levofloxacin,as well as higher in-hospital mortality than the non-CRKP group,with statistically significant differences(all P＜0.05).Acute pancreatitis prior to infection(OR=16.564,P＜0.001),hypoalbuminemia(OR=8.588,P＜0.001),stay in in-tensive care unit prior to infection(OR=2.733,P=0.017),blood transfusion(OR=3.968,P=0.001),broncho-scopy(OR=5.194,P=0.014),surgery within 30 days prior to infection(OR=2.603,P=0.010),and treatment with carbapenems(OR=2.663,P=0.011)were independent risk factors for the development of CRKP blood-stream infection(BSI).Cardiac insufficiency before infection(OR=11.094,P=0.001),combined with pulmonary infection(OR=20.801,P=0.010),septic shock(OR=9.783,P=0.002),disturbance of consciousness(OR=11.648,P=0.001),and receiving glucocorticoid treatment(OR=5.333,P=0.018)were independent risk factors for mortality in patients with CRKP BSI.Conclusion The resistance rate of KP from BSI to tigecycline and com-pound sulfamethoxazole presents upward trend.Underlying diseases,invasive procedures,and carbapenem treat-ment are closely related to CRKP BSI.Cardiac insufficiency,pulmonary infection,septic shock,disturbance of con-sciousness,and glucocorticoid treatment can lead to death of patients with CRKP BSI.

Quality evaluation of Huanglian Shangqing tablets(pills and granules)based on GC characteristic chromatogram of volatile oil / 中国药师

Objective To establish the GC characteristic choromatogram of Huanglian Shangqing tablets(pills and granules),and to investigate the quality of the medicinal materials(Weeping Forsythia,Mentha Hyplocalyx and Herba Schizonepetae)containing volatile oil in Huanglian Shangqing tablets(pills and granules).Methods Agilient HP-5 capillary column(30 m×0.32 mm,0.25 μm)was used with temperature programming,the split ratio was 5∶1,the split flow was 5 mL·min-1,the injection volume was 1 μL,and the inlet temperature was 250℃.A hydrogen flame ionization detector was used,with the detector temperature of 260℃,and the column flow was 1 mL·min-1.The quality of samples from different manufacturers was evaluated by using the GC characteristic choromatogram of volatile oil and the identification of characteristic peaks,combined with similarity analysis and principal component analysis.Results The characteristic chromatograms of 192 batches of samples from 56 manufacturers were established.The peaks of Weeping Forsythia,Mentha Hyplocalyx and Herba Schizonepetae were identified as α-pinene and β-pinene,menthol and menthone,and pulegone respectively.The GC choromatogram of volatile oil components in Huanglian Shangqing tablets(pills)from different manufacturers were quite different,and some peaks of indicator components in the products from a few manufacturers have missing.Conclusion The established GC characteristic chromatograms can reflect the product quality status and can be used for the quality evaluation and product quality control of Huanglian Shangqing tablets(pills and capsules).Huanglian Shangqing tablets(pills and capsules)from some manufacturers are insufficient in the active ingredients of volatile oil,therefore,the product quality needs to be improved.

Analysis on the current situation of hospice care service in a district of Beijing / 中华医院管理杂志

Objective:To analyze the terminal survey data of hospice care services in a district of Beijing in 2020, and discuss its current situation and existing problems of hospice care services in this district for countermeasures, hence providing reference for the development of hospice care services.Methods:Data were collected from the " Terminal Survey Forms of the Second Batch of Hospice Care Pilot Areas in China in 2020" , which were reported by 4 tertiary hospitals and 5 community health service centers in a district of Beijing. The reporting timeframe ranged from January to December 2020. Text analysis method was used to analyze the hospice care mode, relevant security policies, hospice care team, case diagnosis categories, average hospitalization days and patient cost burden. All the data were subject to descriptive analysis.Results:In 2020, only 4 tertiary hospitals carried out outpatient, consultation and inpatient services of hospice care among the 9 medical institutions in a certain district of Beijing, and none of them carried out home hospice care services. The number of doctors and nurses engaged in hospice care in the four hospitals was 35 and 40 respectively; There were 267 inpatient cases of hospice care, including 121 cases of malignant tumors, accounting for 45.32%; The average hospitalization days of hospice patients (40.0 days) was more than that of the hospital (7.8 days); The average daily hospitalization cost of hospice patients (3 428.7 yuan) was lower than that of the hospital (3 605.6 yuan); Hospice care services had not been included in the scope of medical insurance payment, and the relevant security policies were not perfect.Conclusions:The work of hospice care service in a district of Beijing remains at an initial stage, and the professional team building and supporting policies for hospice care fail to catch up with the demand in this district. The authors suggest to speed up the development of hospice care in primary medical institutions, build a network of " hospital -community-family" levels, enhance training of professionals and technical personnel of hospice care, as well as establish and improve the medical security system, so as to promote the rapid development of hospice care services in this district.

Risk factors and prognosis analysis of carbapenem-resistant Klebsiella pneumoniae infection for inpatients in hepatobiliary surgery / 中华肝胆外科杂志

Objective:To explore the risk factors and prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection for inpatients in hepatobiliary surgery. Methods:The clinical data of patients with Klebsiella pneumoniae infection admitted to the Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital from January 2016 to December 2020 were retrospectively analyzed. For each patient with CRKP infection, two patients with non-carbapenem-resistant Klebsiella pneumoniae (non-CRKP) infection were selected for matching. A total of 720 patients with Klebsiella pneumoniae infection were involved, including 444 males and 276 females, aged (58.0±11.6) years old. According to the infection conditions, they were divided into two groups: CRKP group ( n=240) and non-CRKP group ( n=480). The 240 CRKP patients were divided into two subgroups according to their prognosis: death group ( n=34) and survival group ( n=206). The general information, laboratory test results, antibiotic use and infection outcomes of patients were recorded to analyze the risk factors of infection and death after infection. Results:Acute pancreatitis ( OR=3.473, 95% CI: 1.844-6.541), chronic cardiovascular disease before infection ( OR=2.028, 95% CI: 1.228-3.347), chronic renal failure ( OR=1.873, 95% CI: 1.142-3.073), hypoalbuminemia ( OR=3.060, 95% CI: 1.869-5.010), use of carbapenems ( OR=3.882, 95% CI: 2.518-5.985), admission to intensive care unit ( OR=1.783, 95% CI: 1.034-3.075) and surgery within 30 days before infection ( OR=13.463, 95% CI: 7.482-24.223) were independent risk factors for CRKP infection inpatients in hepatobiliary surgery(all P<0.05). Chronic respiratory disease before infection ( OR=3.784, 95% CI: 1.420-10.089), mechanical ventilation ( OR=5.085, 95% CI: 1.436-18.011), disturbance of consciousness ( OR=40.710, 95% CI: 3.564-464.943), hormone therapy ( OR=14.977, 95% CI: 3.819-58.743) and treatment of quinolone antibiotics ( OR=4.102, 95% CI: 1.226-13.726) were independent risk factors for death of inpatients with CRKP infection in hepatobiliary surgery (all P<0.05). The resistance of amikacin, tobramycin, ceftazidime, cefepime, aztreonam, ciprofloxacin, levofloxacin, co-sulfamethoxazole and piperacillin/tazobactamand in CRKP group were significantly different compared with non-CRKP group (all P<0.05). Conclusion:The occurrence of CRKP infection for inpatients in hepatobiliary surgery is related to various factors such as underlying diseases, antibiotic use and self-barrier destruction, and these factors affect the infection outcome of patients.

Observation of the efficacy and safety of the Song-Relaxing and Zhen-Vibrating abdomen manipulation for patients with prediabetes / 针灸推拿医学（英文版）

Objective: To observe the safety of the Song-Relaxing and Zhen-Vibrating abdomen manipulation in treating patients with prediabetes and its effects on blood glucose and lipid metabolism.Methods: One hundred and two patients with prediabetes were divided into a manipulation group and a control group according to the random number table method, with 51 cases in each group. All patients received the general behavioral intervention for prediabetes, with additional Song-Relaxing and Zhen-Vibrating abdomen manipulation in the manipulation group and oral metformin hydrochloride tablets in the control group. Both groups received the intervention for six months. Results: Fourteen patients dropped out during the treatment, and a total of 88 patients completed the trial, including 45 cases in the manipulation group and 43 cases in the control group. After the treatment, the prediabetes control rate was 93.3％ in the manipulation group and 74.4％ in the control group, and the difference between the two groups was statistically significant (P<0.05); no patient in the manipulation group progressed to diabetes, while the rate of conversion to diabetes in the control group was 6.9％, with a significant difference between the two groups (P<0.05). After the treatment, the body mass index (BMI), glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour postload plasma glucose (2hPG) level during an oral glucose tolerance test (OGTT), fasting insulin (FINS), homeostasis model assessment-2 of insulin resistance (HOMA2-IR), total cholesterol (TC), and triglycerides (TG) decreased in both groups versus baseline, with significant differences within the groups; the levels of all indicators were lower in the manipulation group than in the control group (P<0.05), and the differences between the two groups were more prominent at the sixth month (P<0.01). At the sixth month, the high-density lipoprotein cholesterol (HDL-C) in the manipulation group was increased, while there was no significant change in the control group. In the control group, three patients reported mild gastrointestinal reactions at the initial dosing, which improved after medication adjustment. No other adverse events were observed in either group. Conclusion: Both metformin hydrochloride tablets and the Song-Relaxing and Zhen-Vibrating abdomen manipulation can improve blood glucose and lipid metabolism and reduce insulin resistance and clinical discomfort in patients with prediabetes, but the Song-Relaxing and Zhen-Vibrating abdomen manipulation has higher efficacy and safety.

Research progress of coagulation dysfunction in coronavirus disease 2019 / 中华危重病急救医学

The coronavirus disease 2019 (COVID-19) has outbroken globally. As an acute infectious disease, COVID-19 has significant impacts on multiple organs and systems throughout the body. Among patients with COVID-19, especially severe and critical cases, a variety of potential risk factors for coagulation dysfunction exist. Furthermore, the coagulation dysfunction of COVID-19 patients was mainly characterized by elevated D-dimer levels. The coagulation dysfunction could directly affect the prognosis of COVID-19 patients and is a major cause of death in patients with severe COVID-19. In this article, the literatures on the basic clinical manifestations, clinical risk factor, mechanism of coagulation dysfunction and evaluation of coagulation function in COVID-19 were reviewed.

Long-term efficacy and safety of electroacupuncture on improving MMSE in patients with Alzheimer's disease / 中国针灸

OBJECTIVE@#To observe the efficacy and safety of electroacupuncture (EA) on improving mini-mental state examination (MMSE) in patients with Alzheimer's disease (AD), and to evaluate the efficacy during follow-up visit.@*METHODS@#Forty patients were randomly divided into a treatment group and a control group, 20 patients in each one (3 patients dropped off in the treatment group and 4 patients in the control group). The patients in the treatment group were treated with acupuncture at Baihui (GV 20), Fengfu (GV 16), Shenting (GV 24), Taiyang (EX-HN 5), Shangyintang (Extra 3) and Dazhong (KI 14); besides, EA was applied at Taiyang (EX-HN 5), Baihui (GV 20) and Shenting (GV 24) with dilatational wave, 10 Hz/50 Hz in frequency, 0.5 to 5.0 mA in intensity, once every two days, three treatments per week. The patients in the control group were treated with oral administration of donepezil hydrochloride tablets, once a day, taken before sleep. The treatment was given for 12 weeks in the two groups. The MMSE was evaluated before treatment, 12 weeks±3 days into treatment, and 24 weeks±7 days after treatment, respectively.@*RESULTS@#The difference of total score of MMSE before and 12 weeks±3 days into treatment was not significant between the two groups (>0.05); the total score of MMSE after treatment was higher than that before treatment (both <0.05); compared before treatment, the short-term memory score was increased in the treatment group (<0.05), and the increasing range was superior to that in the control group (<0.05). Compared before treatment, the total score of MMSE in the two groups were reduced 24 weeks ±7 days after treatment (both <0.05), and the reduction in the treatment group was less than that in the control group (<0.05); the differences of short-term memory score before and after treatment was significant between the two groups (<0.05). No adverse reaction occurred in the two groups.@*CONCLUSION@#The effect of EA on improving MMSE in patients with AD is similar to donepezil supported by evidence-based medicine. The effect of EA may have a certain continuous effect, and may have advantages in instantaneous memory. In addition, the EA is safe.

Analysis of the changes of blood immune indicators in 291 cases of voluntary blood donors / 国际检验医学杂志

Objective To investigate the changes of lymphocyte subsets of 291 blood donors after dona-tion.Methods 291 cases of voluntary blood donors were enrolled in the study from January 2016 to December 2016.Before and 30 d after blood donation,cellular immune function and humoral immune function.The cellu-lar immune function and humoral immune function of 30 d before and after blood donation were compared,the changes of cellular immune function and humoral immune function before and after donation of 30 d between different genders.Results 30 d after blood donation,CD3+,CD4+lymphocytes and CD4+/CD8+were higher than those before blood donation(P<0.05).There was no significant difference in the levels of IgA,IgM and IgG before and after blood donation(P> 0.05).30 d after blood donation,CD3+,CD4+lymphocytes,and CD4+/CD8+were all higher than those before blood donation in both males and females(P<0.05);CD3+, CD4+lymphocytes,and CD4+/CD8+were detected before and after blood donation,between different genders there was no significant difference(P>0.05).There was no significant difference between males and females in IgA,IgM and IgG before and after blood donation(P>0.05).Conclusion There was no significant change in the humoral immune function in 291 cases of voluntary blood donors,but the proportion of T cell subsets increased.

Protective role and mechanism of dexmedetomidine on the LPS-stimulated PC12 cells / 解放军医学杂志

Objective To explore the effect ofdexmedetomidine on the lipopolysaccharide (LPS) stimulated PC12 cells and its potential mechanism.Methods PC12 cells were treated by LPS with a concentration of 400μg/ml.The cell viability,the concentrations ofinterleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the cell culture supernatant were measured after 3-,6-,or 12-h treatment.The expressions of toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MyD88) and phosphorylated p65 (p-p65) were measured.In the second part,PC12 cells were cultured under four different treatments,that is,normal culture media in first group,400μg/ml LPS in second group,100μmol/L dexmedetomidine in third group,400μg/ml LPS and100μmol/L dexmedetomidine in fourth group.The indexes mentioned above were measured 6 hours after LPS and DEX treatments.Results The cell viability was decreased after LPS treatment,and the concentrations of IL-6 and TNF-α were increased significantly.Compared with control group,the concentrations in 3-,6-,12-h groups showed statistically significant differences (P＜0.05),especially after 6 hours.The TLR4/MyD88/NF-κB pathway was activated after LPS stimuli and reached the peak value.Compared with LPS treatment group,PC 12 cell apoptosis rate,the concentrations of IL-6 and TNF-α and the expressions of TLR4,MyD88 and p-p65 were decreased.The differences between LPS+DEX group and LPS group was statistically significant (P＜0.05).Conclusion Dexmedetomidine has a protective effect on LPS stimulated PC 12 cells via the inhibition of inflammatory response.

Detection of Na+/H+exchanger regulatory factor 3 protein expression in renal carcinoma and its correlation with malignant biological behavior / 中国医师进修杂志

Objective To study the detection of Na+/H+exchanger regulatory factor 3(NHERF3) protein expression in renal carcinoma and its correlation with malignant biological behavior. Methods Renal clear cell carcinoma and their adjacent tissues of forty- eight patients were collected. Immunohistochemical method was used to detect the positive expression of NHERF3 protein,and specific expression was detected by Western-blot.Patients were further divided into high NHERF3 group and low NHERF3 group according to median expression of NHERF3 protein,and each group had 24 cases.The expressions of proliferation,invasion and autophagy genes in tumor tissues were detected by fluorescent quantitative PCR.Results The positive rate of NHERF3 protein and the expression of NHERF3 protein in renal carcinoma tissue was significantly lower than that in paracancerous tissue(P<0.05).Expressions of proliferation genes such as k-Ras,c-Myc,TRPC1 mRNA in low NHERF3 group were higher than those in high NHERF3 group:141.74 ± 18.95 vs. 100.00 ± 0.00, 135.88 ± 16.32 vs. 100.00 ± 0.00, 137.21 ± 16.98 vs.100.00 ± 0.00;MIIP,FOXO1 mRNA levels were lower than those in high NHERF3 group: 43.19 ± 5.88 vs. 100.00 ± 0.00, 38.76 ± 4.51 vs. 100.00 ± 0.00; expressions of invasion genes such as CD74, Fascin, MACC1, TRPM8 mRNA were significantly higher than those in high NHERF3 group:152.18 ± 17.64 vs. 100.00 ± 0.00, 146.29 ± 17.63 vs. 100.00 ± 0.00, 139.76 ± 15.82 vs. 100.00 ± 0.00,150.47 ± 17.95 vs.100.00 ± 0.00;expressions of autophagy genes such as Beclin-1,LC3 mRNA were significantly lower than those in high NHERF3 group: 63.21 ± 7.09 vs. 100.00 ± 0.00, 56.28 ± 7.15 vs. 100.00 ± 0.00; EZH2 mRNA level was higher than that in high NHERF3 group:159.47 ± 17.82 vs.100.00 ± 0.00,and there were significant differences(P<0.05).Conclusions The positive rate of NHERF3 protein expression and the amount of protein expression in renal carcinoma tissue is increased, and the specific expression is closely related to tumor proliferation, invasion and activity of autophagy.

The Wuhan Twin Birth Cohort Study / 中华流行病学杂志

The prevalence of child and adolescent growth and mental-behavior related diseases are increasing,and the pathogcnesis are complex.Twins are excellent natural resources for complex chronic diseases research as they share the maternal intrauterine environment,born at the same time and share the same family environment in early years,which could benefit the adjust ment of confounding factors,such as age,genetic factors and early family environmental factors.Birth cohort with twin families involved could be more effective in exploring the genetic and environmental factors for complex chronic diseases at the very beginning of life.This paper summarizes the objective,content,progress,strengths and potential problems of Wuhan Twin Birth Cohort,with emphasis on the overall design and progress of the study.

The Wuhan Twin Birth Cohort Study / 中华流行病学杂志

The prevalence of child and adolescent growth and mental-behavior related diseases are increasing, and the pathogenesis are complex. Twins are excellent natural resources for complex chronic diseases research as they share the maternal intrauterine environment, born at the same time and share the same family environment in early years, which could benefit the adjust ment of confounding factors, such as age, genetic factors and early family environmental factors. Birth cohort with twin families involved could be more effective in exploring the genetic and environmental factors for complex chronic diseases at the very beginning of life. This paper summarizes the objective, content, progress, strengths and potential problems of Wuhan Twin Birth Cohort, with emphasis on the overall design and progress of the study.

Progresses in understanding trauma-induced coagulopathy and the underlying mechanism / 中华创伤杂志(英文版)

Trauma-induced coagulopathy (TIC) is a clinical syndrome caused by imbalance between clotting, anti-coagulation and fibrinolysis resulting from multiple pathological factors such as hemorrhage and tissue injury in the early stage of trauma, and is closely related to the outcome of trauma patients. It is proved in growing evidence that the endogenous coagulation disturbance in trauma itself is the activating factor of TIC, rather than dilution or other acquired coagulopathy. Therefore, a thorough understanding of the molecular mechanisms in the pathogenesis and progression is crucial for effective prevention and treatment in patients with TIC. This review focuses on transitions in the concept of TIC and mechanical progress.

Role and mechanism of endoplasmic reticulum stress and Ca2+ overload in pulmonary endothelial cell damage induced by heat stress / 解放军医学杂志

Objective To observe the effect of different temperatures on endoplasmic reticulum stress, calcium overload, mitochondria and cell damage in pulmonary microvascular endothelial cells (PMVEC) induced by heat stress, and clarify the mechanism of endothelial cell injury in the process of heat stress to provide experimental basis for clinical prevention and treatment of heat stree. Methods Heat stress model of PMVEC cell was set up. Control group cells were incubated at 37℃, 5%CO2, while heat stress group cells were incubated at 39℃, 41℃, 43℃ for 2h, respectively, then further incubated at 37℃, 5%CO2 for 6h. Pretreatment of cells with 20μmol/L BAPTA-AM or 50μmol/L CsA before heat stress at 43℃. The protein levels of p-PERK, PERK p-eIF2a, eIF2a, ATF4 and GRP78 were analyzed by Western blotting. Intracellular Ca2+, mitochondrial membrane potential and the changes in mitochondrial permeability transition pore were investigated by flow cytometry. The change of caspase-3 was detected by Caspase Assay Kit. Millicell-ERS Volt-Ohm Meter and Accessories was used for determining the changes of transepithelium electrical resistance (TER). Results Compared with the control group, with the increase of heat stress temperature (41-43℃), the phosphorylation of p-PERK and p-eIF2a protein and the expressions of ATF4 and GRP78 proteins were gradually activated, intracellular Ca2+ increased, MPTP pore was opened, mitochondrial membrane potential decreased, cell permeability increased and apoptosis occurred, and it was the most obvious in the 43℃ heat stress group, and the difference was statistically significant (P<0.05). Pretreatment with Ca2+ inhibitors promoted the recovery of the MPTP hole, mitochondrial membrane potential and cell permeability, and reduced the occurrence of apoptosis. While pretreatment with the mitochondrial protective agent did not reduce the release of Ca2+, but it could promote the recovery of cell permeability and reduce the occurrence of apoptosis. Conclusion Heat stress activates endoplasmic reticulum stress response, induces intracellular Ca2+ overload mediated cell and mitochondrial damages in PMVEC cells, which may be one of the important mechanisms of endothelial cell injury induced by heat stress.

Clinical analysis of peripherally inserted central catheters guided by B-ultrasound / 局解手术学杂志

Objective To analyze and summarize the clinical effect of peripherally inserted central catheters (PICC) guided by B-ultrasound,and to discuss the catheterization skills of PICC guided by B ultrasound.Methods Retrospectively analyzed the clinical data of 102 patients recieved PICC guided by ultrasound in neurosurgery department of Chongqing emergency medical center from January 2016 to May 2017.The success rate of one-time puncture, the success rate of one-time catheter delivery and the number of complications were analyzed, and the causes and treatment methods of complications were analyzed.Results Of the 102 cases,94 cases were successfully punctured in one time,6 cases were punctured twice,and 2 cases were punctured more than 2 times.The one-time puncture success rate was 92.16%.Catheter misplacement occurred in 5 patients,and postoperative complications occurred in 2 patients.Conclusion Mastering the related angiotomy and imaging knowledge of PICC and using the B-ultrasound guidance system to insert the catheter can improve the success rate of catheterization and reduce the postoperative complications.

Protective effects of heat shock protein 70 on the acute lung injury of rats with heat stroke and its mechanism / 解放军医学杂志

Objective To investigate the protective effect of heat shock protein (HSP) 70 on the acute lung injury (ALI) of rats with heat stroke.Methods Sixty four rats were randomly (by employing a random number table) assigned into a sham-heated group (Sham group),heat stress group (HS group),and HS plus gluttamine treatment group (HS+GLN group) and HS plus quercet in treatment group (HS+QU group),16 each.All rats were housed in a artificial climate chamber,with the rats in the sham groups exposed to a temperature of 23 ℃ and humidity of 55％ ± 5％,while the rats of HS,HS+GLN and HS+QU groups to an ambient temperature of 39 ℃ and humidity of 65％.During heat stress or sham heating,rectal temperature (Tr),systolic blood pressure (SBP) and pulse rate (PR) were monitored to observe the difference in heat stress response among the groups.The time point at which the SBP started to drop from the peak level was taken as the point of HS onset.At the onset of HS,heat exposure was terminated,then the rats were immediately removed from the chamber,and returned to room temperature.The rats were scarified 0h and 6h after HS onset respectively.After bronchoalveolar lavage fluid (BALF) was collected,the lungs of all animals were harvested for pathological examination of lung injury.The concentrations of IL-1β,TNF-α and IL-6 in BALF and HSP70 in lung homogenate were measured by using an enzyme linked immunosorbent assay kit.Results Compared with HS and HS+QU groups,the rats in HS+GLN group required significantly greater heat load to induce HS (P＜0.001),and had longer survival time span after HS onset.Compared with Sham group,the concentration of HSP70 in lung homogenate in HS group increased in a time-dependent manner (P＜0.001).In comparison with HS group,the concentration of HSP70 in lung homogenate from HS+GLN group was significantly elevated at each time point (P＜0.001),while the treatment with QU significantly inhibited the expression of HSP70 (P＜0.001).The concentration of IL-1β,TNF-α and IL-6 in BALF significantly decreased in HS+GLN group compared with those in HS group and HS+QU group (P＜0.001).The pathological results showed that the lung injury was milder in HS+GLN group,while the opposite in HS+QU group.Conclusion HSP70 could protect HS rats against ALI by enhancing their thermo-tolerance and inhibiting inflammatory response.

The role of oxidative stress in the acute liver injury of rats with heat stroke and its mechanism / 解放军医学杂志

Objective To investigate the role of oxidative stress in acute liver injury in a heat stroke model of conscious rats,and to explore its underlying mechanism.Methods Thirty-two rats were randomly (by using a random number table) assigned into a sham-heated control group (Sham group,n=8),a sham-heated group treated with NAC (Sham-NAC group,n=8),a heat stroke group (HS group,n=8) and a heat stoke group treated with NAC (HS-NAC,n=8).Rats were prepared with pre-warm chamber to initiate heat stoke.The change of rectum temperature (Tr),heart rate (HR) and systolic blood pressure (SBP) were monitored,and the time point of HS onset was recorded.Rats were sacrificed 12h after HS onset.ALT,serum TBIL,IL-6,IL-1β,TNF-α,MDA,T-SOD and GSH in the liver homogenates were measured.Liver tissues were harvested for determining the concentration of reactive oxygen species (ROS),neutrophil infiltration and the histological changes.Results During HS onset,no significant differences were observed in Tr,HR,SBP and heat exposure time between HS group and HS-NAC group (P＞0.05).However,the survival time was significantly longer in HS-NAC group than in HS group (P=0.039).12 hours after HS onset,the concentrations of ROS and MDA in the liver homogenates were significantly higher in HS group than in the other groups (P=0.000),while the concentrations of T-SOD and GSH were much lower than in the other groups (P=0.000).The serum concentrations of ALT and TBIL were significantly higher in HS group than in the other groups (P=0.000).Compare with HS group,the pathological injury was alleviated in HS-NAC group (P=0.000).The neutrophil infiltration level and the concentrations of IL-6,IL-1 β and TNF-α in liver tissue were significantly higher in HS group than in HS-NAC group (P=0.000).Conclusion Oxidative stress may play an important role in the pathogenesis of HS liver injury through its cytotoxic effect and by inducing inflammatory responses.

Effects of gradient heat stress on phagocytosis of liver Kupffer cells in vitro / 解放军医学杂志

Objective To investigate the effect of gradient heat stress on phagocytosis of hepatic Kupffer cells (KCs) in vitro in rats. Methods Rat Kupffer cells were isolated in vitro and the temperature for gradient heat stress was set at 37, 39, 41 and 43℃. After thermal stimulation, cell injury was detected by PI and Hochest33342 staining. CCK-8 assay was used to investigate difference in cellular proliferation rate over 24h between the groups. Flow cytometry was used to investigate the influence of heat stress on the phagocytosis of KCs. Results Compared to the normal control group, cells in each heat stress group exhibited varying degrees of damage, especially cells in 43℃ group. The ratio of damage cells increased with the increase of heat stress severity (P<0.05). Proliferation assay indicated that the proliferation rate of cells in each heat stress group was significantly decreased in comparison with normal control group 6h after heat stress (P<0.05). After 12h recovery, decrease in proliferation rate was observed only in 43℃ group (P<0.001), and no difference in the rate of proliferation could be observed between the heat stress groups and normal control group after 24h recovery. Flow cytometry showed, that the phagocytosis of KCs decreased in heat stress groups compared with control group, especially in 43℃ group (P<0.05). This phenomenon disappeared after 24h recovery. Conclusion Heat stress can inhibit the phagocytosis of rat liver KCs through its cytotoxic effect on KCs, and subsequently inhibits its proliferative ability. Further investigation of the effect of heat stress on KCs may help understand the pathogenesis of heat stress.