Herbal Textual Research on Pharbitidis Semen in Famous Classical Formulas / 中国实验方剂学杂志

By consulting the ancient and modern literature， the textual research of Pharbitidis Semen has been conducted to clarify the name， origin， distribution of production areas， quality specification， harvesting， processing and so on， so as to provide reference for the development and utilization of the relevant famous classical formulas. Through textual research， it can be seen that Pharbitidis Semen was first published in Mingyi Bielu（《名医别录》）， and all dynasties have taken Qianniuzi as the correct name. Based on the original research， the main source of Pharbitidis Semen used in previous dynasties is the dried mature seeds of Pharbitis nil， which is consistent in ancient and modern times. The white Pharbitidis Semen appearing in Compendium of Materia Medica（《本草纲目》） from Ming dynasty is similar to the present P. purpurea. It is produced all over the country， and the quality is better if the particles are full and free of impurities. In ancient times， the harvesting time was mostly in the September. Now it is autumn. The fruits are ripe and harvested， dried to remove impurities for standby. In ancient times， the processing methods of Pharbitidis Semen were mainly wine steaming， steaming and frying until half cooked and grinding the head and end. In modern times， they have been simplified to stir-frying method. The nature， taste， meridian tropism and their effects also change supplements with the deepening of practice. Before the Ming dynasty， they were all bitter， cold and toxic. In the Ming dynasty， there appeared the characteristics of pungent， hot and small poisonous. The efficacy has evolved from controlling low Qi， curing foot edema， removing wind toxin， and facilitating urination to facilitating water and defecation， eliminating phlegm and drinking， and eliminating accumulated insects. The main clinical contraindications are those with weak spleen and kidney， those with weak spleen and stomach， pregnant women， and should not be used with croton and croton cream. Based on the textual research， it is suggested that when developing the classic famous formula with Pharbitidis Semen as the main raw material in the future， it is clear that the source should be the dried mature seeds of Pharbitis nil（black product is its black-brown seeds， white product is its beige seeds）. The processing requirements indicated in the original formula are all processed according to the requirements， and the raw product is recommended to be used as medicine if not specified.

Ameliorative effects of a Chinese herbal formula, fufang meidengmu on uterine leiomyoma in a mice model.

Fufang Meidengmu (FFMDM) is an ethnic herbal medicine form Yunnan province of China, which is often used for the treatment of uterine leiomyoma (UL). Combined Gancao (Glycyrrhiza uralensis Fisch.) and Haizao (Sargassum pallidum (Turn.) C.Ag) in FFMDM represent an herbal pair in the so-called "eighteen antagonistic medicaments" according to traditional Chinese medicine. In this study, we explored the prevention and treatment effects of FFMDM component compatibility on UL in mice. Female Kunming mice were injected for different periods of time with different concentrations of estradiol benzoate (EB) to investigate a feasible method to establish a mice model of UL. Treatment with 0.3mg/kg EB for 15 days was found to be the optimal condition for UL mice models. We then investigate the role of Gancao and Haizao in FFMDM, and explored the underlying mechanism of action of UL mice. Our findings suggested that Gancao and Haizao exerted the favorable effects. In addition, FFMDM is effective in the treatment of UL, and its mechanism was associated with the estrogen (ER) and progesterone receptors (PR).

Rapid health technology assessment of Xuesaitong injection in the treatment of stroke / 中国药房

OBJECTIVE To evaluate the efficacy， safety and economical efficiency of Xuesaitong injection in the treatment of stroke by rapid health technology assessment，so as to provide evidence for clinical rational drug use. METHODS Retrieved from Wanfang database， CBM， CNKI，PubMed，Cochrane Library，Embase， INAHTA and HTAI databases or organization websites， health technology assessment （HTA） reports， meta-analysis/systematic reviews and pharmacoeconomic studies related to Xuesaitong injection in the treatment of stroke were summarized and analyzed. RESULTS A total of 29 pieces of literature were included. Among them， 14 studies were conducted on meta-analysis/systematic reviews，15 studies were conducted on pharmacoeconomics， HTA was not obtained. The results of meta-analysis/systematic reviews showed that Xuesaitong injection had certain advantages for stroke in improving the total effective rate， clinical symptoms and related scale scores compared with blank control group and some drug control groups. Safety studies had shown that the adverse reactions of Xuesaitong injection were mainly allergic-like reactions. The results of pharmacoeconomic evaluation are quite different， which may also be related to the long time span among various studies and the adjustment of some drug prices. CONCLUSIONS Xuesaitong injection in the treatment of stroke is helpful to improve the clinical efficacy and evaluation indexes， but there are some serious adverse reactions， and it is not economically superior to some chemical drugs.

Advances in neural circuits of innate fear defense behavior / 浙江大学学报·医学版

Fear, a negative emotion triggered by dangerous stimuli, can lead to psychiatric disorders such as phobias, anxiety disorders, and depression. Investigating the neural circuitry underlying congenital fear can offer insights into the pathophysiological mechanisms of related psychiatric conditions. Research on innate fear primarily centers on the response mechanisms to various sensory signals, including olfactory, visual and auditory stimuli. Different types of fear signal inputs are regulated by distinct neural circuits. The neural circuits of the main and accessory olfactory systems receive and process olfactory stimuli, mediating defensive responses like freezing. Escape behaviors elicited by visual stimuli are primarily regulated through the superior colliculus and hypothalamic projection circuits. Auditory stimuli-induced responses, including escape, are mainly mediated through auditory cortex projection circuits. In this article, we review the research progress on neural circuits of innate fear defensive behaviors in animals. We further discuss the different sensory systems, especially the projection circuits of olfactory, visual and auditory systems, to provide references for the mechanistic study of related mental disorders.

Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) / 中华危重病急救医学

The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.

Study on the mechanism of Chonghe paste promoting the dissipation of swollen lesions in vivo and in vitro / 中国药房

OBJECTIVE To explore the mechanism of Chonghe paste promoting the dissipation of swollen lesions. METHODS The bacteriostatic effects of Chonghe paste against Staphylococcus aureus， Escherichia coli， Pseudomonas aeruginosa， Staphylococcus albus and Streptococcus pneumoniae were detected by punching method. The subcutaneous soft tissue infection model of rats was established by subcutaneous injection of S. aureus. The effects of 14 d intervention of Chonghe paste （Compound polymyxin B ointment as positive control） on the pathological changes of subcutaneous soft tissue， the protein expressions of type Ⅰ collagen， type Ⅲ collagen， matrix metalloproteinase-2 （MMP-2） and MMP-9 in subcutaneous soft tissue， and the contents of transforming growth factor-β （TGF-β） and basic fibroblast growth factor （bFGF） in serum were investigated. RESULTS Chonghe paste had varying degrees of bacteriostatic effect on the above 4 bacteria （except for S. pneumoniae）， especially on S. aureus. Compared with the model group， on the 7th day of treatment， collagen fibers in the Chonghe paste group were arranged in an orderly manner， pus dissipated faster； the protein expressions of type Ⅰ and type Ⅲ collagen and the contents of TGF-β and bFGF were up-regulated significantly， while protein expressions of MMP-2 and MMP-9 were decreased significantly （P＜0.05）. On the 14th day of administration， collagen deposition was obvious in the Chonghe paste group， subcutaneous appendages gradually formed； the protein expressions of type Ⅰ and type Ⅲ collagen and the contents of TGF-β and bFGF were down-regulated significantly， while the protein expressions of MMP-2 and MMP-9 were increased significantly （P＜0.05）. CONCLUSIONS Chonghe paste has the bacteriostatic effect and may play a role in promoting the dissipation of swollen lesions by regulating the formation and decomposition of fibrin and increasing the secretion of bFGF and TGF-β.

Yajieshaba prevents lipopolysaccharide-induced intestinal barrier injuryanti-inflammatory and anti-apoptosis.

OBJECTIVE: To investigate the protective effect of Yajieshaba (YJSB) on the intestinal barrier dysfunction induced by lipopolysaccharide (LPS). METHODS: C57BL/6 mice and rat intestinal epithelial cells were treated with LPS. Thiazolyl Blue Tetrazolium Bromide assay were used to detect cell viability. D-Lactate, diamine oxidase and myeloperoxidase and cytokines were determined by enzyme-linked immunosorbent assay. Western blot was used to detect apoptosis-related proteins and tight junction (TJ) proteins. Real-time quantitative polymerase chain reaction was used to quantify the levels of mRNA expression of cytokines. Histological analysis was performed by hematoxylin and eosin staining. An immunofluorescence staining assay was performed to determine the expression level of TJ protein. RESULTS: YJSB increased cell viability and decreased apoptosis, maintained intestinal permeability after LPS-induced. YJSB inhibited LPS-induced decrease of TJ protein expression, pro-inflammatory cytokine levels and neutrophil infiltration. CONCLUSION: YJSB protect against LPS-induced intestinal barrier dysfunction anti-inflammatory and anti-apoptosis, suggesting its therapeutic potential against intestinal barrier injury-related diseases.

Retracted: Anticancer Activity of Mukonal Against Human Laryngeal Cancer Cells Involves Apoptosis, Cell Cycle Arrest, and Inhibition of PI3K/AKT and MEK/ERK Signalling Pathways.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. Reference: Liu Li, Lu Huizhi, Wang Binu, Deng Xinxin, Wu Longjun, Yang Liping, Zhang Yingying. Anticancer Activity of Mukonal Against Human Laryngeal Cancer Cells Involves Apoptosis, Cell Cycle Arrest, and Inhibition of PI3K/AKT and MEK/ERK Signalling Pathways. Med Sci Monit, 2018; 24: 7295-7302. DOI: 10.12659/MSM.910702.

GSH-responsive poly-resveratrol based nanoparticles for effective drug delivery and reversing multidrug resistance.

Cancer poses a serious threat to human health and is the most common cause of human death. Polymer-based nanomedicines are presently used to enhance the treatment effectiveness and decrease the systemic toxicity of chemotherapeutic agents. However, the disadvantage of currently polymeric carriers is without therapy procedure. Herein, for the first time, glutathione (GSH)-responsive polymer (PRES) with anti-cancer effect was synthesized following the condensation-polymerization method using resveratrol (RES) and 3,3'-dithiodipropionic acid. PRES can not only suppress the tumor cells growth but can also self-assemble into nanoparticles (∼93 nm) for delivering antitumor drugs, such as paclitaxel (PTX@PRES NPs). The system could achieve high drug loading (∼7%) and overcome multidrug resistance (MDR). The results from the in vitro studies revealed that the NPs formed of PRES were stable in the systemic circulation, while could be efficiently degraded in tumor cells high GSH environment. Results from cytotoxicity tests confirmed that PTX@PRES NPs could effectively suppress the growth of cancer cells (A549) and drug-resistant cells (A549/PTX). The NPs could also be used to significantly increase the therapeutic efficacy of the drugs in A549/PTX tumor-bearing mice. In vivo investigations also demonstrated that the PRES-based NPs exhibited tumor inhibition effects. In summary, we report that the GSH-responsive polymer synthesized by us exhibited multiple interesting functions and could be used for effective drug delivery. The polymer exhibited good therapeutic effects and could be used to overcome MDR. Thus, the synthesized system can be used to develop a new strategy for treating cancer.

Innovation and practice of endoscope-assisted nipple-sparing mastectomy combined with immediate subpectoral implant breast reconstruction without gas and mesh through small skin incisions / 中华内分泌外科杂志

Objective:To examine the feasibility and safety of endoscopic subcutaneous mastectomy and immediate reconstruction via a small skin incision approach without gas and mesh for early breast carcinomas.Methods:We analyzed 7 patients diagnosed with breast cancer who underwent an endoscopic subcutaneous mastectomy and immediate reconstruction from Jun. to Nov. 2021 using a gasless and meshless small skin incision approach at the Department of Thyroid and Breast Surgery, the First Affiliated Hospital of USTC. Mean age was 44.9 (29-63) years. Clinical stage, postoperative complications and other data of patients were collected. Patients were required to fill in BREAST-Q scale anonymously before and during postoperative follow-up. The difference was considered significant for P < 0.05. Results:The tumors were all unilateral and solitary lesions, with a mean diameter of 1.74 (0-5) cm. The average distance of mass from the nipple on imaging was 2.11cm (range 0 to 4) . Postoperative pathological clinical stage,1 patient was in Tis, 3 patients were in stage I, 2 patients were in stage II and a pathological complete response was achieved in one patient (ypT0pN0cM0 CR) . The mean operative time was 245.3 (195-316) min, the mean intraoperative bleeding volume was 37.1ml, the mean postoperative hospital stay was 5.1 d, and the median follow-up time was 8.8 (6-11.2) months. All the 7 patients had incision healing at the first stage, and no complications such as infection, incision complications, capsular contracture, nipple-areola complex or skin flap necrosis, removal or displacement of breast implant occurred. No local recurrence or metastasis was detected during the follow-up period. Compared with preoperative, the scores of postoperative psychosocial status, chest wall status were lower ( P<0.05) , but still ideal, while breast satisfaction and sexual satisfaction scores were not significantly different from preoperative baseline ( P>0.05) . Conclusion:This study indicates that endoscope-assisted breast reconstruction with gasless and meshless is a safe and feasible surgical intervention method for early breast cancer, with good cosmetic effects, and can be promoted as a new type of breast reconstruction.

Field epidemiological investigation of a varicella outbreak in a school of Nanxun District， Huzhou / 上海预防医学

ObjectiveTo determine the epidemiological characteristics and transmission factors of a varicella outbreak in a school in Nanxun District of Huzhou City， and assess the effect of prevention and control measures， which may provide scientific evidence for improvement in the response to varicella outbreak. MethodsData were collected by field epidemiological survey and analyzed by descriptive epidemiology. Statistical analysis was performed by SPSS 22.0 software. ResultsA total of 80 varicella cases were identified in this outbreak， which lasted 68 days. There were four peaks of incidence， involving 21 classes. The total incidence rate was determined to be 4.14%. Before the public health intervention， some cases were not isolated in time， which led to the initial spread in the class. After the mid-term examination， the outbreak further spread to multiple classes. Breakthrough varicella cases accounted for 48.75% of all the cases in the outbreak， among which 94.87% had been vaccinated for more than five years. However， there was no significant difference in the incidence of fever and rash between the breakthrough cases and non-breakthrough cases（P>0.05）. ConclusionTimely report， prompt response， and strict implementation of prevention and control measures remain crucial for effective containment of varicella outbreak.

Clinical significance of the determination of fecal short-chain fatty acids in patients with nonalcoholic fatty liver disease / 临床肝胆病杂志

Objective To investigate the association of the metabolism of intestinal short-chain fatty acids (SCFAs) with the development and progression of the disease spectrum of nonalcoholic fatty liver disease (NAFLD) by determining the content of fecal SCFAs in patients with different NAFLD diseases and the change in the content of fecal SCFAs after treatment in patients at a high risk of nonalcoholic steatohepatitis (NASH). Methods A total of 90 patients who were diagnosed with NAFLD in The Affiliated Hospital of Qinghai University from July 2020 to July 2021 were enrolled and divided into simple nonalcoholic fatty liver (NAFL) group with 30 patients, NASH group with 30 patients, and nonalcoholic fatty liver fibrosis group with 30 patients, and 40 individuals who underwent physical examination during the same period of time were enrolled as control group. Related case data and fecal SCFAs content were collected for the four groups, and related clinical indices and fecal SCFAs content were collected for 10 patients at a high risk of NASH after 3 months of intervention. The analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the paired samples t -test was used for comparison within each group; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the paired samples Wilcoxon signed rank sum test was used for comparison within each group; a Spearman correlation analysis was used to investigate the correlation between variables; the receiver operating characteristic (ROC) curve analysis was used for diagnostic evaluation. Results Compared with the control group, the nonalcoholic fatty liver fibrosis group had significantly higher contents of valeric acid and caproic acid, and the NAFL group had significantly lower contents of valeric acid and caproic acid (all P < 0.05); the nonalcoholic fatty liver fibrosis group had significantly higher contents of valeric acid and caproic acid than the NAFL group ( P < 0.05); the nonalcoholic fatty liver fibrosis group had a significantly higher content of valeric acid than the NASH group ( P < 0.05); the NASH group had a significantly higher content of caproic acid than the NAFL group ( P < 0.05). After treatment, the high-risk patients in the NASH group had significant reductions in HbA1c, fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bile acid (TBA), prothrombin time (PT), uric acid (UA), controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) ( Z =-2.805, -2.703, -2.193, -2.599, -2.805, -2.701, -2.803, -1.988, -2.807, -2.803, -2.803, and -2.668, all P < 0.05); for these patients, the contents of acetic acid and propionic acid after treatment were significantly higher than those before treatment ( Z =-2.803 and -2.803, both P < 0.05), and the content of isobutyric acid after treatment was significantly lower than that before treatment ( Z =-2.803, P < 0.05). In the diagnosis of nonalcoholic fatty liver fibrosis, valeric acid had an area under the ROC curve (AUC) of 0.842, with a sensitivity of 86.7% and a specificity of 70% at the optimal cut-off value of 141.42 μg/g; caproic acid had an AUC of 0.819, with a sensitivity of 70% and a specificity of 85% at the optimal cut-off value of 6.93 μg/g. Conclusion Valeric acid and caproic acid may promote the development of NAFLD disease spectrum. Acetic acid and propionic acid may have a certain protective effect on the liver of NAFLD patients, and isobutyric acid may promote the development and progression of NASH. The protective effect of acetic acid and propionic acid on the liver may further lead to the reductions in HbA1c, FPG, TG, TC, ALT, AST, GGT, TBA, PT, UA, CAP, and LSM. Valeric acid and caproic acid have an inferior diagnostic value to PIIIP N-P and a superior diagnostic value to type IV collagen and hyaluronic acid. Valeric acid with the optimal cut-off value of 141.42 μg/g and caproic acid with the optimal cut-off value of 6.93 μg/g can be used as the auxiliary diagnostic indicators for the early diagnosis of nonalcoholic fatty liver fibrosis.

WWC2-AS1/miR-382-5p/FZD3 axis regulates proliferation and apoptosis of ovarian granulosa cells in polycystic ovary syndrome / 中华内分泌外科杂志

Objective:To investigate the role of WWC2-AS1/miR-382-5p/FZD3 in granulosa cell (GCs) of polycystic ovary syndrome (polycystic ovarian syndrome, PCOS) patients and its molecular mechanism.Methods:Bioinformatics tools were used to predict the molecular mechanism of PCOS. The expressions of WWC2-AS1, miR-382-5p and FZD3 in serum and GCs of patients with PCOS and healthy controls were detected by qRT-PCR. The effects of WWC2-AS1/miR-382-5p/FZD3 on the proliferation and apoptosis of GCs were observed by CCK-8 and flow cytometry. The interaction between WWC2-AS1 and miR-382-5p, miR-382-5p and FZD3 was verified by double luciferase report experiment.Results:Compared with the control group, the expression of WWC2-AS1 and FZD3 in serum and GCs of PCOS patients was significantly up-regulated, while the expression of miR-382-5p was down-regulated. Silencing WWC2-AS1 could significantly promote the proliferation of GCs in PCOS and inhibit the apoptosis of GCs (all P<0.05) . There is a WWC2-AS1/miR-382-5p/FZD3 interaction network in PCOS, and miR-382-5p inhibitor or overexpressed FZD3 can partially reverse the regulatory effect of silent WWC2-AS1 on GCs in PCOS. Conclusion:This study shows that WWC2-AS1 regulates miR-382-5p and up-regulates FZD3, which promotes the proliferation of GCs and inhibits apoptosis in the progression of PCOS. WWC2-AS1/miR-382-5p/FZD3 may be an effective molecular target for the treatment of PCOS.

Plasma-exosomal miR-18a-3p regulates CITED2 expression to affect cumulus cells apoptosis and cell cycle distribution in polycystic ovary syndrome / 中华内分泌外科杂志

Objective:To investigate the effect of plasma exosome miR-18a-3p on of apoptosis and cell cycle cumulus cells (CCs) in polycystic ovary syndrome (PCOS) via targeting CITED2.Methods:qRT-PCR assay was used to detect the expression of miR-18a-3p in plasma, plasma-derived exosome and CCs of patients no matter with PCOS and non PCOS. After being transfected with miR-18a-3p mimic, the exosome was co-cultured with CCs, the cell cycle distribution and apoptosis of CCs were detected by flow cytometry assays. Gene ontology (GO) analysis was performed and CITED2 was included in follow up experiments. pcDNA3.1-CITED was transfected into CCs and then co-cultured with exosome to explore the co-effect of miR-18a-3p and CITED2 on the cell cycle and apoptosis of CCs.Results:The plasma-derived exosome isolated from CCs with PCOS were identified successfully, and the expression of miR-18a-3p was significantly decreased in plasma, exosome and CCs in PCOS, compared with that in non-PCOS (all P<0.05) . CITED2 could be regulated as a target of miR-18a-3p in CCs. Compared with NC group, overexpression of miR-18a-3p could significantly decrease proportion of CCs cells in G0/G1 phase and inhibit their apoptosis in PCOS patients (all P<0.05) . The effect of over-expressing miR-18a-3p could be partially reversed by up-regulating CITED2 (all P<0.05) . Conclusions:Plasma exosomal miR-18a-3p has the effect to induce the S phase of CCs cells, subsequently inhibit apoptosis, then restrain the progression of PCOS. Plasma exosomal miR-18a-3p is expected to play a paramount role in the target therapy of PCOS.

Epidemiological parameter estimation and characteristics of the novel coronavirus disease (COVID-19) transmission in Shaanxi Province / 公共卫生与预防医学

Objective To estimate the key epidemiological parameters, including the serial interval (SI), basic reproduction numbers (R0), and time-dependent reproduction numbers (Rt) based on the case data of COVID-19 published on the official website of Shaanxi Provincial Health Commission. Methods The method of maximum likelihood estimation was used to fit the probability distribution of SI, and three parametric models including Gamma, Weibull, and Lognormal distributions were adopted to estimate the distribution of SI. The optimal model was selected by the corrected Akaike information criterion (AICc). Based on nonlinear regression model the cumulative number of confirmed cases was fit to the growth rate r of the Richard growth model to estimate R0. The Rt was calculated based on the Bayesian framework. Results A total of 49 transmission chains were discovered from 245 local confirmed cases in Shaanxi Province. The Gamma distribution was the optimal model to fit the SI here by AICc. Using the Gamma distribution, the mean SI was estimated to be 6.3 days (95%CI:5.98 - 6.43) with a standard deviation (SD) of 3.94 days (95%CI: 3.01 - 5.03). Using the Richard growth model, the growth rate was estimated to be 0.23 (95% CI: 0.21 - 0.24) and the basic reproduction number in Shaanxi to be 3.11 (95%CI: 2.91 - 3.40). Rt showed an overall downward trend, and fell below 1 on February 10 (Rt=0.95（95%CI: 0.76-1.16)), and stabilized at around 0.35 on February 18. Conclusion The SI of COVID-19 is relatively shorter than that of MERS and SARS, while the R0 is relatively larger, and Rt is on a downward trend, which suggests COVID-19 is a highly transmissible infectious disease. The control measures including the isolation and treatment of confirmed patients, quarantine and observation of suspected cases, contact tracing, improvement of public awareness, and adoption of self-protection measures can effectively reduce the COVID-19 outbreak.

Early mobilization on mortality of patients with mechanical ventilation in intensive care unit after discharge: a Meta-analysis / 中华危重病急救医学

Objective:To evaluate the effect of early mobilization on mortality in intensive care unit (ICU) patients with mechanical ventilation after discharge by Meta-analysis.Methods:Databases including SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang data, PubMed, the Cochrane Library, Web of Science, and Embase were searched from inception to September 17th, 2020, to collect randomized controlled trials (RCT) about early mobilization on mortality of patients with mechanical ventilation in ICU after discharge, the references included in the literature were traced. The control group was given routine care, the experimental group was given early mobilization on the basis of the control group, including passive or active mobilization on the bed, sitting on the bed, standing by the bed, transferring to the bedside chair and assisting walking. The literature screening, data extracting, and the bias risk assessment of included studies were conducted independently by two reviewers. Stata 12.0 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 10 RCT studies involving 1 323 patients were included, with 660 patients in the control group and 663 patients in the experimental group. The results of literature quality evaluation showed that 7 studies were grade A and 3 studies were grade B, indicating that the overall quality of included literatures was high. The Meta-analysis results showed that early mobilization did not increase the mortality of patients with mechanical ventilation in ICU after discharge [odds ratio ( OR) = 0.92, 95% confidence interval (95% CI) was 0.75-1.13, P = 0.449]. Subgroup analysis results showed that early mobilization had a tendency to reduce the mortality of ICU patients with mechanical ventilation at 3, 6 and 12 months after discharge, but the difference was not statistically significant (3-month mortality: OR = 1.02, 95% CI was 0.74-1.40, P = 0.927; 6-month mortality: OR = 0.95, 95% CI was 0.70-1.27, P = 0.712; 12-month mortality: OR = 0.60, 95% CI was 0.33-1.10, P = 0.101). Funnel plot showed that the distribution of included literatures was not completely symmetrical, suggesting that publication bias might exist. Conclusions:Early mobilization does not increase the mortality of ICU patients with mechanical ventilation after discharge. Although it tends to have a favorable outcome in reducing mortality, and has a trend to reduce the mortality. However, due to the small number of included literatures, small sample size and differences in the specific implementation of early mobilization among various studies, a large number of high-quality RCT studies are still needed for further verification.

Analysis of a pedigree affected with hereditary coagulation factor XI deficiency due to compound heterozygous variants of F11 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a Chinese pedigree affected with coagulation factor XI (FXI) deficiency.@*METHODS@#Activated partial thromboplastin time (APTT) and other blood coagulation factors, and activities of FXI:C and other relevant coagulation factors for a large Chinese pedigree including 6 patients from 3 generations were determined on a Stago automatic coagulometer. The FXI:Ag was determined with an ELISA method. All exons and flanking regions of the F11 gene were subjected to Sanger sequencing. ClustalX-2.1-win software was used to analyze the conservation of amino acids. Pathogenicity of the variants was predicted with online bioinformatics software including Mutation Taster and Swiss-Pdb Viewer.@*RESULTS@#The APTT of the proband was prolonged to 94.2 s. The FXI:C and FXI:Ag were decreased to 1% and 1.3%, respectively. The APTT of her father, mother, son and daughter was 42.1 s, 43.0 s, 42.5 s and 41.0 s, respectively. The FXI:C and FXI:Ag of them were almost halved compared with the normal values. The APTT, FXI:C and FXI:Ag of her husband were all normal. Genetic testing revealed that the proband has carried a heterozygous missense c.1103G>A (p.Gly350Glu) variant in exon 10 and a heterozygous missense c.1556G>A (p.Trp501stop) variant in exon 13 of the F11 gene. The father and daughter were heterozygous for the c.1103G>A variant, whilst the mother and son were heterozygous for the c.1556G>A variant. Both Gly350 and Trp501 are highly conserved among homologous species, and both variants were predicted to be "disease causing" by Mutation Taster. Protein modeling indicated there are two hydrogen bonds between Gly350 and Phe312 in the wild-type, while the p.Gly350Glu variant may add a hydrogen bond to Glu and Tyr351 and create steric resistance between the two, both may affect the structure and stability of protein.@*CONCLUSION@#The c.1103G>A and c.1556G>A compound heterozygous variants probably underlay the pathogenesis of congenital FXI deficiency in this pedigree.

The effect of trauma care systems on the mortality of injured adult patients: A protocol for systematic review and meta-analysis.

PURPOSE: The aim of this study was to have a comprehensive evaluation of the effect of trauma care systems on the mortality of injured adult patients. MATERIALS AND METHODS: This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Web of Science, PubMed, EMBASE, Scopus, and the Cochrane Library were searched for all clinical trials evaluating the effect of trauma care systems on the mortality of injured adult patients until July 31, 2020. We will use a combination of Medical Subject Heading and free-text terms with various synonyms to search based on the eligibility criteria. Two investigators independently reviewed the included studies and extracted relevant data. The odds ratio (OR) and 95% confidence intervals (CIs) were used as effect estimate. I-square (I) test, substantial heterogeneity, sensitivity analysis, and publication bias assessment will be performed accordingly. Stata 15.0 and Review Manger 5.3 are used for meta-analysis and systematic review. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: The results of this review will be widely disseminated through peer-reviewed publications and conference presentations. This evidence may also provide a comprehensive evaluation of the effect of trauma care systems on the mortality of injured adult patients. REGISTRATION NUMBER: INPLASY202080058.

Cognitive impairment after intensive care unit discharge: a Meta-analysis / 中华危重病急救医学

Objective:To investigate the cognitive impairment after intensive care unit (ICU) discharge and provide theoretical basis for prevention and intervention.Methods:Studies about cognitive impairment after ICU discharge were retrieved in PubMed, Embase, Cochrane Library, Web of Science, Wanfang data, CNKI and SinoMed from their foundation to December 2019. The literature screening and data extraction were performed by two researchers independently, and the quality of different types of researches was evaluated using Cochrane Handbook 5.1.0, Newcastle-Ottawa scale (NOS) and agency for healthcare research and quality criteria (AHRQ). The Meta-analysis was performed by Stata 13.0 software. Sensitivity analysis was used to determine the reliability of the combined effect values. Funnel plot and Egger test were used to analyze publication bias. The non-parametric clipping was used to evaluate the impact of publication bias on the results.Results:A total of 35 studies were enrolled, including 27 prospective cohort studies, 4 retrospective cohort studies, 2 randomized controlled trial (RCT) studies, 1 case-control study, and 1 cross-sectional study. Three literatures were published in Chinese and 32 were in English, which covered 13 countries, and a total of 102 504 ICU survivors were followed up successfully. Literature quality evaluation results showed that the NOS scores of 31 cohort studies were between 6 and 9, of which the case-control study scored 9. The quality grade of 2 RCT studies were both B. According to the AHRQ criteria, 1 cross-sectional study's design was scientifically rigorous and of high quality. Thirty-five studies reported that the overall incidence of cognitive impairment after ICU discharge ranged from 2.47% to 66.07%. For the multiple follow-ups studies, the first survey data was selected for Meta-analysis, and the results showed that the pooled incidence was 38.44% [95% confidence interval (95% CI) was 29.32-47.55]. Each study was removed for sensitivity analysis and the pooled results did not change much, which indicated that the results were reliable. The sub-group analysis was performed on different evaluation methods for cognitive impairment after ICU discharge, different types of ICU patients, and different follow-up time. The results showed that the pooled incidence of studies using neuropsychological test to evaluate cognitive impairment after ICU discharge was 31.42% (95% CI was 21.82-41.02), the pooled incidence of studies using questionnaires or scales was 38.75% (95% CI was 29.54-47.96), and the difference between the two groups was statistically significant ( P < 0.01). The pooled incidence of cognitive impairment after ICU discharge in general ICU patients was 43.42% (95% CI was 30.88-55.95), acute respiratory distress syndrome (ARDS) patients' pooled incidence was 34.40% (95% CI was 23.02-45.79), and the pooled incidence of elderly ICU patients was 12.93% (95% CI was 8.48-17.37), the difference among the three groups was statistically significant ( P < 0.01). The incidences of cognitive impairment < 1 year, 1 to 4 years, ≥ 5 years after ICU discharge were 43.30% (95% CI was 29.47-57.13), 34.21% (95% CI was 26.70-41.72), and 20.22% (95% CI was 4.89-35.55), respectively, and the differences among the three groups were statistically significant ( P < 0.01). The funnel plot showed that the distribution of all studies was asymmetric, and the Egger test result also suggested that there might be publication bias ( P < 0.05). The non-parametric clipping was used to estimate the impact of publication bias on the results, and the result showed that the difference in the incidence of cognitive impairment after ICU discharge before and after non-parametric clipping was large, suggesting that publication bias might influence the stability of the research results. Conclusions:The incidence of cognitive impairment after ICU discharge is relatively high and persistent for a long time, but diagnostic criteria of cognitive impairment and follow-up time are quite different. It is necessary to develop consistent evaluation criteria and rigorous designed research in the further.

Evaluation of pharmaceutical prevention and treatment of intensive care unit-acquired weakness: a Meta-analysis / 中华危重病急救医学

Objective:To evaluate the effect of preventing and treatment of pharmaceuticals on intensive care unit-acquired weakness (ICU-AW) by systematic review.Methods:The randomized controlled trials (RCTs) concerning pharmaceutical prevention and treatment about ICU-AW in SinoMed, CNKI, Wanfang data, PubMed, Cochrane Library, Web of Science, EMbase, and other sources were searched from their foundation to May 30th, 2019. The patients in the intervention group were treated with drugs to prevent or treat ICU-AW; and those in control group were treated with other rehabilitation methods. Data searching, extracting and quality evaluation were assessed by two reviewers independently. Stata 12.0 software was then used for Meta-analysis. Only descriptive analysis was conducted when only one study was enrolled.Results:A total of 11 RCTs were enrolled with 1 865 patients in the intervention group and 1 894 in the control group. The results of quality evaluation showed that 4 studies were A-level and 7 studies were B-level, indicating that the overall quality of the enrolled literature was high. Meta-analysis showed that intensive insulin therapy could prevent ICU-AW [relative risk ( RR) = 0.761, 95% confidence interval (95% CI) was 0.662-0.876, P = 0.000], but reduced phenylalanine loss (nmol·100 mL -1·min -1: -3±3 vs. -11±3, P < 0.05) and glutamine intake (nmol·100 mL -1·min -1: -97±22 vs. -51±13, P < 0.05). There was no significant difference in the prevention and treatment of ICU-AW between other drugs (including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin) and control group. Conclusions:Intensive insulin therapy can prevent ICU-AW, but the risk of hypoglycemia will increase. Other drugs including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin have no obvious advantages in the prevention and treatment of ICU-AW, so no drug has been recommended to prevent and treat ICU-AW.