Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the Cmax Values of minocycline were(541±137)ng·mL-1 for the test formulation and(558±140)ng·mL-1for the reference formulation.The AUC0-t values were(8 347±1 986)h·ng·mL-1 for the test and(8 205±1 790)h·ng·mL-1 for the reference.The t1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the Cmax values of minocycline were(349±72.1)ng·mL-1 for the test and(352±73.2)ng·mL-1for the reference.The AUC0-twere(6 428±1 077)h·ng·mL-1 for the test and(6 588±1 118)h·ng·mL-1 for the reference.The t1/2values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were(90.84%,101.46% ),(95.2%,102.8% ),and(95.31%,102.71% ),respectively.Under fed conditions,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test formulation and the reference formulation were(94.71%,103.42% ),(95.40%,99.83% ),and(95.79%,100.02% ),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.

Objective:To investigate the establishment method, coordination points and safe transport management strategy of vena-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with downtime difficulties during cardiopulmonary bypass (CPB).Methods:A observation study was conducted. The patients admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from January 2020 to October 2022 were enrolled. These patients could not be separated from CPB and received VA-ECMO-assisted CPB surgery. The clinical data of the patients were recorded, including the basic information of the patients, the data of VA-ECMO establishment and transport process, the clinical indicators before and after VA-ECMO installation, the operation data of VA-ECMO and clinical outcomes. The experience was summarized from the aspects of extracorporeal membrane oxygenation (ECMO) establishment, transport process, team cooperation, and adverse events during transport. The clinical indicators before and after ECMO operation were compared. According to whether ECMO was successfully weaned, the patients were divided into a successful weaning group and a failure weaning group, and the clinical data between the two groups were compared.Results:Eighteen patients who underwent VA-ECMO-assisted CPB were enrolled, including 10 males and 8 females. The average age was (56.7±12.3) years old. Preoperative left ventricular ejection fraction (LVEF) was 0.46±0.10, and the main reasons for switching to VA-ECMO assistance included right ventricular systolic weakness in 6 cases, total cardiac systolic weakness in 5 cases, left ventricular systolic weakness in 4 cases, high pulmonary arterial pressure in 2 cases, and intractable ventricular fibrillation in 1 case. Among the 18 patients transferred from CPB to VA-ECMO, 10 cases were successfully weaned and 8 cases failed. In ICU, 8 cases survived, 5 cases died, and 5 cases gave up treatment and discharged. The average time for successful CPB to VA-ECMO establishment was (24.6±7.4) minutes, initial blood flow was (3.3±0.4) L/min, and transit time was (8.4±1.5) minutes. ECMO-assisted duration averaged (82.0±69.3) hours. Adverse events occurred in 9 patients during ECMO establishment and transfer. Post-ECMO onboarding for 4 hours, significant improvements were noted in blood lactic acid (Lac), pH value, mean arterial pressure (MAP), central venous oxygen saturation (ScvO 2) as compared with pre-ECMO onboarding [Lac (mmol/L): 10.5±7.0 vs. 15.2±6.8, pH value: 7.38±0.92 vs. 7.26±0.87, MAP (mmHg, 1 mmHg≈0.133 kPa): 74.9±13.7 vs. 58.4±17.0, ScvO 2: 0.678±0.065 vs. 0.611±0.061, all P < 0.01], and vasoactive-inotropic score (VIS) was also decreased (39.8±29.8 vs. 68.9±64.4, P < 0.01). Compared with successful weaning group, the patients in the failed weaning group exhibited higher pre-machine Lac (mmol/L: 18.8±7.8 vs. 12.3±4.3, P < 0.05), longer CPB time [minutes: 238.0 (208.8, 351.2) vs. 200.0 (185.8, 217.0), P < 0.05], and shorter ECMO-assisted time [hours: 19.5 (11.0, 58.8) vs. 94.5 (65.8, 179.8), P < 0.01]. However, there was no statistically significant difference in pre-machine pH value, ScvO 2, MAP, VIS score, and initial blood flow and establishment time of ECMO between the two groups. Conclusions:VA-ECMO is an effective circulatory aid for CPB surgery that cannot be weaned after CPB. The establishment and transfer of CPB "bridge" to ECMO aid depends on multi-disciplinary treatment (MDT) cooperation. The success rate of ECMO weaning is related to the Lac and CPB duration. If it is not possible to detach from the CPB successfully, VA-ECMO should be initiated as early as possible.

Objective:To integrate the best evidence for early rehabilitation of mechanically ventilated ICU-acquired weakness (ICU-AW) patients using evidence-based methods, providing evidence-based basis for standardized evaluation and intervention of early exercise therapy for mechanically ventilated ICU-AW patients.Methods:A systematic search was conducted on the American Thoracic Society (ATS) Clinical Practice Guidelines, Registered Nurses' Association of Ontario (RNAO), Guidelines International Network (GIN), Canadian Medical Association Clinical Practice Guideline Library (CMACPGL), BMJ Clinical Evidence, UpToDate, Scottish Intercollegiate Guidelines Network (SIGN), PubMed, Cochrane Library, National Guideline Clearinghouse (NGC), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), UM-library, Physiotherapy Evidence Database (PEDro), National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Chinese Medical Pulse Guidelines Website, CNKI and Wanfang data and other Chinese and English databases, professional team websites, and guideline websites for expert consensus, guidelines, randomized collected trial (RCT), systematic reviews and other evidence on early exercise rehabilitation for mechanically ventilated ICU-AW patients. The search time limit was from the establishment of the database to December 31, 2023. Literature search, screening, evaluation, information extraction was independently conducted by two evaluators with cross checking, and quality evaluation of the included literature was conducted.Results:A total of 21 literatures were enrolled, including 5 guidelines, 5 systematic reviews, 4 expert consensuses, and 7 RCT, all of which with high evidence level and all were enrolled. They were summarized into seven aspects with assessment screening, exercise safety standards, precautions, setting of exercise time, exercise intensity, exercise sequence, and recommended exercise content as the core, and 32 best evidences.Conclusions:The evidence summarized can provide evidence-based basis for standardized assessment and intervention of early exercise rehabilitation in mechanically ventilated ICU-AW patients. ICU medical practitioners need to combine the actual clinical environment, individual differences and rehabilitation goals of patients, to provide targeted health guidance and intervention for the prevention of ICU-AW in mechanically ventilated patients.

Objective:To explore the application effect of ICU nursing sub-specialty management model in the clinical treatment of ICU patients.Methods:Based on the actual needs of ICU patients,a precise and systematic management plan including organizational structure,workflow,linkage mechanism,quality control system,dynamic follow-up,and scientific research transformation was formulated,to construct a working model of multi-linkage,multi-direction supplement and coordinated development of two-way feedback mechanism in sub-specialty nursing.The control group was set before the implementation of ICU nursing sub-specialty management mode(Jan 1 to Dec 31,2021),and the intervention group was set after the implementation of ICU nursing sub-specialty management model(Jan 1 to Dec 31,2022).The core competence,specialty,sensitive indicators,satisfaction,and impact on patients were compared before and after implementation.Results:After the implementation of the ICU nursing sub-specialty management model,the core competence of nurses was improved,and the hospitalization time and mechanical ventilation time of patients were reduced,the incidence of re-entry ICU,acquired weakness,acquired dysphagia and incontinence dermatitis was decreased,the proportion of unplanned extubation was decreased,and the satisfaction of patients,nurses,doctors and students was improved(P＜0.05).Conclusion:The construction of ICU nursing sub-specialty management model can effectively promote the construction of ICU nursing sub-specialty,improve the core competence of nurses,reshape the connotation of nursing,improve the prognosis of patients,and ultimately promote the benign and sustainable development of hospital nursing.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

OBJECTIVE: To explore the predictive value of diaphragmatic thickening fraction (DTF) combined with Medical Research Council-score (MRC score) on the outcome of weaning from mechanical ventilation in ICU-acquired weakness (ICU-AW) patients. METHODS: A retrospective case-control study was conducted. The clinical data of mechanically ventilated patients with an MRC score of less than 48 admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from January 2022 to March 2023 were collected, including general information, ultrasound indicators, MRC scores, main clinical outcomes, and weaning outcomes. Patients were divided into successful weaning group and failed weaning group according to whether the patient could maintain effective autonomous breathing for at least 48 hours without using an invasive or non-invasive ventilator. The clinical data of the two groups were compared. Receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of DTF and MRC score alone or in combination for successful weaning of patients. RESULTS: A total of 87 patients were enrolled, of which 58 were successful weaning and 29 were failed weaning. There were no statistically significant differences in general data such as gender, age, underlying disease, heart rate (HR), mean arterial pressure (MAP), pH value, blood lactic acid (Lac), oxygenation index (PaO₂/FiO₂), and severity scores between the two groups. Compared with the failed weaning group, the DTF and MRC scores of patients in the successful weaning group were significantly increased [DTF: (26.02±2.68)% vs. (22.79±5.40)%, MRC score: 38.90±2.78 vs. 33.24±3.78, both P < 0.05]. The duration of mechanical ventilation and the length of ICU stay of patients in the successful weaning group were significantly shorter than those in the failed weaning group [duration of mechanical ventilation (hours): 102.21±32.60 vs. 113.14±41.34, length of ICU stay (days): 6.48±2.18 vs. 10.11±4.01, both P < 0.05], and the re-intubation rate and ICU hospitalization cost were significantly lowered [re-intubation rate: 6.90% (4/58) vs. 27.59% (8/29), ICU hospitalization cost (10 000 RMB): 4.99±0.87 vs. 7.85±2.45, both P < 0.05]. ROC curve analysis showed that the area under the ROC curve (AUC) of DTF and MRC score for predicting successful weaning in ICU-AW mechanical ventilation patients was 0.839 [95% confidence interval (95%CI) was 0.746-0.931] and 0.799 (95%CI was 0.701-0.899), respectively. Using DTF ≥ 25.01% as the optimal cut-off value to predict successful weaning, the sensitivity was 82.76%, and the specificity was 72.41%. Predicting successful weaning based on an optimal cut-off value of MRC score of ≥ 35.50 had a sensitivity of 79.31% and a specificity of 70.69%. Based on the DTF ≥ 25.01% combined with MRC score ≥ 35.50, it was predicted that the weaning would be successful, with an AUC of 0.887 (95%CI was 0.812-0.962), sensitivity increased to 89.70%, and specificity increased to 79.30%. CONCLUSIONS The DTF and MRC score have good guiding value for the selection of weaning timing and predicting the weaning outcomes in ICU-AW patients. Compared with independent DTF and MRC score, the combination of DTF and MRC score improves the predictive value of successful weaning in ICU-AW patients.
Humans ; Respiration, Artificial ; Ventilator Weaning ; Case-Control Studies ; Retrospective Studies ; Intensive Care Units

Objective:To construct a training program for the life care and caring abilities of home caregivers for the aged with cognitive impairment, so as to provide a basis for conducting training.Methods:From April to May 2021, a preliminary training program was developed through literature review and group discussion. From June to July 2021, purposive sampling was used to select 12 experts from Beijing city, Hebei and Hunan provinces to conduct two rounds of Delphi expert consultation, and finally a training program for life care and caring abilities of home caregivers for the aged with cognitive impairment was constructed.Results:The effective recovery rate of the questionnaire from two rounds of expert consultation was 100.00% (12/12). The authority coefficient of 12 experts was 0.891. The Kendall's W of the first, second, and third level indicators in the second round of consultation were 0.417, 0.205 and 0.200 respectively ( P<0.05). After the second round of consultation, the average value of each item's importance assignment was > 3.500, and the coefficient of variation was < 0.250. The final training program for the life care and caring abilities of home caregivers for the aged with cognitive impairment included 4 training modules, 11 training items, and 35 training content. Training forms included PPT teaching, video learning, case analysis, role playing, operational demonstrations, practical exercises, caregiver self-sharing, and other forms. Conclusions:The training program for life care and caring abilities of home caregivers for the aged with cognitive impairment has good scientific and practical significance, and can provide a basis for the training of home caregivers for the aged with cognitive impairment.

Objective:To summarize the treatment process of rapid decrease in blood flow due to centrifugal pump dysfunction during extracorporeal membrane oxygenation (ECMO) and its related thinking.Methods:On September 25, 2021, the ECMO treatment of a 14-year-old boy with severe mycoplasma pneumonia, severe viral pneumonia and acute respiratory distress syndrome (ARDS) admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College was analyzed.Results:Oxygenation of the child was difficult to maintain under invasive mechanical ventilation, and lung consolidation progressed seriously. After evaluation, venous-venous ECMO (VV-ECMO) was implemented, then oxygenation was improved. In the 120th hour after VV-ECMO establishment, the blood flow sudden decreased, the speed was 3 822 r/min, while the flow was only 0.2 L/min, more over there was no change in the flow when the speed was increased. Before that, the ECMO speed was 3 530 r/min, and the flow was up to 3.4 L/min and stable. After rapid screening, it was determined that the centrifugal pump was dysfunction. ECMO was successfully replaced and the flow was satisfactory.Conclusions:At present, most ECMO centers do not routinely monitor the pressure before and after the pump. There is a lack of visual and quantitative techniques or indicators to judge the pump's function, and there is also a lack of corresponding clinical experience in treatment. This paper summarizes the investigation and treatment process of ECMO pump dysfunction of this case to provide reference.

Objective:To explore the effects of Baduanjin combined with resistance exercise in rural elderly.Methods:From May to September 2020, totally 80 aged people from 2 villages in Hebei province were selected by convenient sampling. Patients from one village were randomly included into an intervention group ( n=40) , and patients from the other village were included into a control group ( n=40) . Patients in the control group took daily activities and exercise, and received only health education, while patients in the intervention group practiced Baduanjin combined with resistance exercise in addition to daily activities. The Chinese version of Fried Frailty Phenotype Assessment Components, Time Up and Go Test (TUGT) , Five-Times Sit-to-Stand Test (FTSST) , and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the frailty, balance ability, lower limb muscle strength, and sleep quality of the two groups of rural elderly before and after the intervention. In this study, totally 80 questionnaires were distributed, and 78 valid questionnaires were recovered, accounting for an effective recovery rate of 97.5%. Results:The Chinese version of Fried Frailty Phenotype Assessment Components and PSQI scores of the rural elderly in the intervention group after the intervention were lower than those in the control group and before the intervention, and the differences were statistically significant ( P<0.05) . The TUGT and FTSST time of the rural elderly in the intervention group after the intervention were shorter than those in the control group and before the intervention, and the differences were statistically significant ( P<0.01) . Conclusions:Baduanjin combined with resistance exercise can delay the debilitating state of rural elderly, improve their lower limb muscle strength, balance ability and sleep quality, and enrich their exercise methods.