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.
Humans ; Consensus ; Prone Position ; Wakefulness ; China ; Dyspnea

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

AIM:To investigate the effects of progranulin (PGRN) on the proliferation, apoptosis and inflammatory responses in lipopolysaccharide (LPS)-induced human alveolar epithelial A549 cells and HPAEpiC cells.METHODS:The cells were divided into 4 groups:control group (the normal cultured cells), LPS group [the cells were treated with LPS (10 mg/L)], PGRN+LPS group (the cells were transfected with pcDNA3.1-PGRN plasmids and then treated with LPS), and pcDNA3.1+LPS group (the cells were transfected with pcDNA3.1-EGFP plasmids and then treated with LPS).The cell viability was measured by MTT assay, cell proliferation was measured by BrdU incorporation assay, and cell apoptosis was analyzed by flow cytometry.The expression of PGRN at mRNA and protein levels was detected by RT-qPCR and Western blot.The protein levels of caspase-3, Bcl-2, Bax, IL-1β, IL-6, TNF-α, p65 and p-IκB-α were determined by Western blot.RESULTS:Compared with control group, the cell proliferation rate was decreased (P<0.05), and the apoptotic rate was increased (P<0.05) in LPS group.The protein levels of caspase-3 and Bax were significantly up-regulated (P<0.05), and the expression of Bcl-2 was down-regulated (P<0.05).The protein levels of IL-1β, IL-6 and TNF-α were significantly up-regulated (P<0.05), and the protein levels of p65 and p-IκB-α were enhanced (P<0.05).Compared with LPS group, the cell proliferation rate was increased (P<0.05), and the apoptotic rate was decreased (P<0.05) in PGRN+LPS group.The protein levels of caspase-3 and Bax were significantly down-regulated (P<0.05), and the expression of Bcl-2 was up-regulated (P<0.05).The protein levels of IL-1β, IL-6 and TNF-α were significantly down-regulated (P<0.05), and the protein levels of p65 and p-IκB-α were decreased (P<0.05).CONCLUSION:PGRN over-expression may alleviate LPS-induced abnormal proliferation, apoptosis and inflammatory cytokine production in the A549 cells and HPAEpiC cells, which may be associated with the regulation of NF-κB signaling pathway.

Objective To investigate the clinical effect of tiotropium bromide combined with Seretide in treatment of moderate to severe chronic obstructive pulmonary disease( COPD) patients. Methods From Jan. 2012 to Oct. 2013,76 severe COPD were selected as our subjects and they were randomly divided into the control group(38 cases)and research group(38 cases). Patients in control group were used Seretide(1 time both at morning and night,the does was 50 μg/ 500 μg),and in research group were given tiotropium bromide with thiophene beside Seretide(1 time every day). The two groups were received routine treatment,including anti infection,cough and asthma,according to the change of illness. The pulmonary function,blood gas index, respiratory symptoms and 6 minutes walking distance(6 MWD)were recorded. Results Forced expiratory volume in one second( FEV1),forced vital capacity( FCV),FEV1 / FCV of patients in research group after ftreatment were(2. 22 ± 0. 48)L,(3. 28 ± 0. 32)L,(66. 23 ± 9. 22)% respectively,higher than those in the control group,and the differences were significant((1. 78 ± 0. 35)L,(2. 85 ± 0. 47)L,(56. 83 ± 7. 85)% ;t= 5. 39,4. 66,4. 78;P < 0. 01). Partial pressure oxygen(PaO2 )of patients in research group after treatment was (72. 83 ± 5. 28)mmHg,significantly higher than that of control group((65. 36 ± 3. 22)mmHg). However, partial pressure of carbon dioxide( PaCO2 )was(43. 28 ± 3. 52)mmHg,significantly lower than the control group((48. 76 ± 2. 85)mmHg;t = 7. 44,7. 45,P < 0. 01). Dyspnea( MMRC)score in research group was (1. 38 ± 0. 32),lower than the control group(1. 76 ± 0. 35),and 6 MWD was(428. 36 ± 32. 85)m,higher than that of control group((398. 65 ± 28. 38)m;t = 4. 93,4. 21,P < 0. 01). Conclusion The treatment plan of tiotropium bromide combine with Seretide on moderate and severe COPD patients is proved with the better clinical effect and it can improve the partial pressure of oxygen and then promote repair mechanism of lung injury as well as promote the quality of life of patients with ascension.

Background and objective It is unclear how could endostatin effect tumor lymphangiogenesis? hTe aim of this study is to explore inhibitory effect of recombinant human endostatin injection (endostar) on lymphangiogenesis in non-small cell lung cancer (NSCLC) tissue and its effect on circulating tumor cells (CTC) in peripheral blood. Methods Tu-mor-bearing model nude mice were divided into eight groups randomly (n=7), including control group, cisplatin group, several concentration endostar groups and endostar plus cisplatin groups. Continuous administration of Endostar for two weeks, ob-served one week atfer the end of administration. Using HE staining and immunohistochemical staining to diagnose the tumor tissue and suspect metastasis lymph nodes, detected vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3 expression level and microlymphatic vessel density (MLVD) of tumor tissue. Enrichment of circulating tumor cells in peripheral blood used immunomagnetic negative selection strategy, used immunolfuorescence staining to diagnose and count CTCs. Results Microlymphatic vessel density and the positive expression rate of VEGF-C, VEGF-D, VEGFR-3 in three endostar groups and three endostar plus cisplatin groups were signiifcantly less than those in control group and cisplatin group. Microlymphatic vessel density and the positive expression rate of VEGF-C, VEGF-D, VEGFR-3 in endostar plus cisplatin group and endostar group with high endostar concentration were signiifcantly less than those with low endostar concentration;hTere was a signiifcant positive correlation between microlymphatic vessel density and the positive expression rate of VEGF-C, VEGF-D, VEGFR-3. hTe number of circulating tumor cells in endostar plus cisplatin groups were signiifcantly less than that of endostar or cisplatin alone. Conclusion Endostar could inhibit tumor lymphangiogenesis and reduce tumor cells into the bloodstream through the lymphatic. Inhibitory effect concerned with drug concentrationwith a dose-dependant.

ObjectiveTo explore the relationship between circulating tumor cells(CTCs) in the peripheral blood of patients with esophageal squamous cell carcinoma(ESCC) and the physiopathological characteristics of esophageal neoplasms.MethodsUsing negative selection system,we depleted red blood cells(RBCs) in red blood cell lysis buffer,depleted white blood cells (WBCs) with Miltenyi magnetic beads and enriched the rare cells from ESCC patients'peripheral blood.Immunofluorence staining (IF) was adopted to identify CTCs.ResultsCirculating tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma was closely related to cell differentiation grade,the invasion of primary cancer,lymph node status,P-TNM stages,and was rarely related to the sex,age or the location of tumor.ConclusionThe results suggest that circulating tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma may express the development of esophageal cancer and may be served as a tumor marker to evaluate the biological behavior of esophageal cancer.

This study was aimed to identify pET21b-HPV16E2/BL21(DE3) strain and to optimize the expression of human papillomavirus type 16 (HPV16) E2 protein by orthogonal analysis. Four influence factors on two levels were selected to increase the target protein quantity. The four factors were induction time, induction temperature, inductor concentration and cell density. The quantity of HPV16 E2 protein was used as the evaluation parameter. Induced by IPTG, HPV16 E2 protein was analyzed by SDS-PAGE and Western Blot. Target protein was analyzed by GIS imaging system to quantify the protein level. SPSS13. 0 software was applied to analyze the result. Data showed that the expression strain pET211rHPV16 E2/BL21(DE3) was identified correctly. HPV16 E2 protein expressed mainly at insoluble form. The 42KD protein band was identified by SDS-PAGE and Western blot. Orthogonal test was applied on influence factor analysis and expression optimization successfully. Main influence factors were inductor concentration and induction temperature. The optimimum condition of maximum expression quantity was 37 degrees C, 7h, 1.0 mmol/L IPTG and OD600 1.0. In this experiment, orthogonal test could not only be used to analyze the influential factors and promote the target protein expression, but also be used to provide a better experiment method for molecular biological study.
DNA-Binding Proteins ; biosynthesis ; genetics ; Genetic Vectors ; genetics ; Human papillomavirus 16 ; metabolism ; Humans ; Oncogene Proteins, Viral ; biosynthesis ; genetics ; Papillomavirus Infections ; virology ; Recombinant Proteins ; biosynthesis ; genetics

BACKGROUNDChemotherapy is one of the important treatment methods for advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the efficacy of docetaxel combined with carboplatin in treatment of advanced NSCLC.

METHODSSixty-four stage IIIB/IV NSCLC patients were treated with docetaxel (75 mg/m² intravenously, on day 1) and carboplatin (AUC=5 intravenously, on day 2).

RESULTSThe overall response rate (RR) was 42.6%, median survival time (MST) was 14 months, and 1-year survival rate was 45.23%. In initial treatment group, 1-year survial rate was 48.84% and MST was 14 months, and 37.89% and 12 months respectively in retreatment group (P=0.0233). The 1-year survial rate and MST of stage IIIB patients were 44.86% and 15 months, and 39.75% and 12 months respectively in stage IV patients (P=0.0354). There was no significant difference in efficacy between squamous cell carcinoma and adenocarcinoma patients. The major adverse effects were granulopenia, fatigue, nausea, vomiting and alopecia.

CONCLUSIONSThe combination of docetaxel and carboplatin has a high response rate and tolerable side effects in treatment of advanced NSCLC, which can be adopted as both the first-line and second-line treatment.

BACKGROUNDPost-operative adjuvant chemotherapy in non-small cell lung can- cer (NSCLC) has been a highlight around the world. The aim of this study is to investigate the efficacy of adjuvant chemotherapy on the survival of patients with NSCLC after complete resection.

METHODSFrom June 2000 to December 2003, 64 patients with stage IB-IIIA NSCLC were divided into the chemotherapy group, who accepted adjuvant chemotherapy with navelbine+cisplatin (NP) or taxol+carboplatin (TP), and the observation group, who did not accept adjuvant chemotherapy after operation. The 1-, 2-, 3- and 4-year survival rate (SR), median survival time (MST) and disease-free time (DFT) were analyzed by Kaplan-Meier method.

RESULTSThe 1-, 2-, 3- and 4-year cumulated SR in the chemotherapy group was 93.9%, 84.6%, 71.4% and 58.4%, and 93.6%, 83.1%, 63.5% and 43.1% in the observation group respectively. There were statistically significant differences in both the 3- and 4-year survival between the two groups (P < 0.05). The MST was 52 months in the chemotherapy group and 47 months in the observation group respectively (P < 0.05), and the DFT was 19 months and 16 months respectively (P < 0.05).

CONCLUSIONSThe cisplatin- or carboplatin-based adjuvant chemotherapy can improve the survival of NSCLC patients after complete resection.

The mathematical models for simulation of cardiac sodium, potassium and calcium channel kinetics courses and currents were developed to simulate the properties of ionic currents and channel dynamic courses. With modifications of these models, it is possible to make them integrated for simulating the whole process of action potential, thus additional discussion on ionic mechanism could provide a theoretical foundation for further animal experiments and clinical applications.
Action Potentials ; Algorithms ; Calcium Channels ; physiology ; Computer Simulation ; Ion Channels ; physiology ; Membrane Potentials ; Models, Cardiovascular ; Myocytes, Cardiac ; physiology ; Potassium Channels ; physiology ; Sodium Channels ; physiology