This study aimed at conducting retrospective analysis of the clinical symptoms and genetic mutations in 20 children with Gitelman syndrome treated at the Affiliated Children′s Hospital of Nanjing Medical University from August 2015 to November 2022 and also explored the molecular mechanism of the pathogenic high-frequency mutation D486N in the Chinese population.

Objective:To investigate the evidence-based practice of prevention and care of nasal and facial pressure injuries in patients with non-invasive positive pressure ventilation (NPPV) using the knowledge to action framework (KTA), and to explore its effectiveness.Methods:Using an evidence-based nursing approach, an evidence-based practice group was established to formulate a clinical problem, the literature from domestic and international databases were researched for relevant evidence, the evidence was introduced into clinical scenarios, an evidence-based practice plan was developed, and a strategy for applying the best evidence was constructed by conducting a baseline review of healthcare professionals and patients with NPPV, analyzing barriers and promoting factors, and making changes in clinical practice at the organizational level, the practitioner level, and the patient level. Purposive sampling method was used to select the healthcare staff of the cardiac surgical intensive care unit (CSICU) of the Shandong Provincial Hospital Affiliated to Shandong First Medical University, as well as the patients with NPPV admitted from October 1 to November 15, 2023 (pre-evidence-based practice) and November 16 to December 31 (post-evidence-based practice), as the subjects of the study. Through questionnaire analysis, the incidence of nasal and facial pressure injury of NPPV patients, the implementation rate of review indicators of medical staff, the score of the knowledge, belief and conduct of medical staff, and the compliance and comfort of patients before and after evidence-based practice were compared.Results:A total of 52 medical staff were included, aged (28.54±6.50) years old, with 3.00 (1.00, 12.75) years of working experience; 2 doctoral degree holders (3.85%), 4 master degree holders (7.69%), 46 bachelor degree holders (88.46%); 2 with senior title (3.85%), 17 with intermediate title (32.69%), and 33 junior titles (63.46%). Fifty patient questionnaires were collected before and after evidence-based nursing practice; the differences between before and after evidence-based practice in terms of gender, age, body weight, duration of ventilator usage, 24-hour bleeding and total bleeding were not statistically significant and were comparable. Compared with the pre-evidence-based practice, after carrying out the corresponding evidence-based nursing practice, the incidence of nasal and facial pressure injuries of NPPV patients decreased from 16.00% (8/50) to 4.00% (2/50, P < 0.05), the total implementation rate of review indicators of medical staff increased from 79.73% to 94.08% ( P < 0.01), and the total scores of knowledge, belief and conduct were significantly improved (141.96±13.88 vs. 114.65±19.72, P < 0.05), and compliance and comfort of patients were significantly improved (compliance score: 4.60±0.99 vs. 5.82±1.42, comfort score: 4.10±1.63 vs. 6.92±2.33, both P < 0.05]. Conclusion:The application of an evidence-based nursing approach to obtain evidence related to the prevention of nasal and facial pressure injuries in patients with NPPV can be used to guide clinical practice, significantly reducing the incidence of nasal and facial pressure injuries in such patients, improving the implementation rate of review indicators and the knowledge, belief, and conduct scores of medical staff, and enhancing compliance and comfort of NPPV patients.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

CLDN6 is a member of the CLDNs family that is specifically and highly expressed in cancers such as ovarian, testicular, endocervical, liver and lung adenocarcinoma, but hardly expressed in adult normal tissues. CLDN6 is able to activate multiple signaling pathways, which take part in the development and progression of cancer, including promoting tumor growth, migration and invasion, and promoting chemoresistance in cancer. In recent years, CLDN6 has received much attention as a novel target for cancer therapeutics. Many types of anticancer drugs targeting CLDN6 have been developed, including antibody-conjugated drugs (ADC), monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T-cell immunotherapy (CAR-T). This paper briefly summarizes the structure, expression and function of CLDN6 in tumors, and reviews the current status and ideas of developing targeted CLDN6 anticancer drugs.
Signal Transduction ; Immunotherapy ; Antibodies, Monoclonal ; Neoplasms/drug therapy*

Objective:To investigate the effects of levosimendan combined with Shengmai injection on pump failure in patients with acute myocardial infarction and its effects on tissue perfusion and oxygen metabolism. Methods:A total of 110 patients with acute myocardial infarction and pump failure who received treatment in Jiaozhou People's Hospital (South Branch) from July 2019 to December 2020 were included in this study. They were randomly assigned to receive either routine treatments including electrocardiography monitoring, oxygen saturation monitoring, oxygen therapy, dual antiplatelet therapy, statins, vasoactive drugs, and nitrates (control group, n = 55) or levosimendan combined with Shengmai injection based on routine treatments (observation group, n = 55) for 10 successive days. Curative efficacy, cardiac function, tissue perfusion, and oxygen metabolism capacity were compared between the control and observation groups. The 1-month mortality rate was compared between the two groups. Results:Total effective rate was significantly higher in the observation group than in the control group [58.18% (32/55) vs. 38.18% (21/55), χ2 = 4.41, P < 0.05]. After treatment, left ventricular end-diastolic diameter, left ventricular ejection fraction, and stroke volume were superior in the observation group to in the control group ( t = 2.12, –5.85, –7.33, all P < 0.05). Oxygen partial pressure, oxygenation index, central venous oxygen saturation, lactate, lactate clearance rate, and urine volume in the observation group were (103.53 ± 9.85) mmHg, (247.69 ± 18.95) mmHg, (77.56 ± 3.59)%, (3.02 ± 0.45) mmol/L, (42.89 ± 5.22)%, (40.88 ± 1.64) mL/hour, respectively, and they were (95.47 ± 11.98) mmHg, (194.69 ± 16.52) mmHg, (70.88 ± 2.13)%, (3.58 ± 0.51) mmol/L, (36.89 ± 5.14)%, and (36.55 ± 2.23) mL/hour, respectively in the observation group. There were significant differences in these indices between the control and observation groups ( t = –3.85, –15.64, –11.87, 3.11, –6.07, –11.27, all P < 0.001). At 1 month of follow-up, mortality rate was significantly lower in the observation group than in the control group [3.64% (2/55) vs. 16.36% (9/55), χ2 = 4.95, P < 0.05]. Conclusion:Levosimendan combined with Shengmai injection is a highly effective treatment for pump failure in acute myocardial infarction. It can improve cardiac function and tissue perfusion, increase oxygen metabolism capacity, and decrease mortality.

Objective:To investigate the relationship between the blood test results of seven items of thyroid function and intolerance to 14 kinds of foods in physical examination population.Methods:Total of 45 764 participants who received physical examination and accepted 14-kind food intolerance and 7-item thyroid function detection from August 2016 to September 2019 in Chinese People′s Liberation Army General Hospital were included in this study. The data were analyzed based on age, gender, body mass index, smoking and drinking status, and laboratory test indexes. Chi square test and univariate or multivariate logistic regression were applied to analyze the correlation between food intolerance and thyroid function in the physical examination population.Results:In the subjects, there were 29 361 cases (64.16%) with at least intolerance to one kind of food, and 15 011 (32.80%) were in Grade 1, 9 037 (19.75%) in grade 2 and 5 313 (11.61%) in grade 3. The positive rate of egg intolerance was the highest (34.06%), and that of beef intolerance was the lowest (1.24%). Of the participants, 11 337 (24.77%) had at least one item thyroid dysfunction, among them, the highest abnormal rate was found in thyroid stimulating hormone (TSH), followed by anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies. The proportion (26.32%) of abnormal thyroid function in the participants with at least intolerance to one kind of food was significantly higher than that (22.00%) in the participants without intolerance to the 14 kinds of foods ( χ2=105.78, P<0.001). After adjusting for other significantly related factors, the positive results of intolerance to 14 kinds of foods was still the significant influencing factor of thyroid function abnormalities ( OR=1.14, Z=5.68, 95% CI: 1.09-1.20, P<0.001). Further analysis showed that, after adjusted for age, gender, smoking and drinking status, intolerance to four kinds of foods (egg, soybean, crab and pork) were the significant influencing factors of abnormal thyroid function. Conclusions:Food intolerance is an independent risk factor of thyroid dysfunction. Among them, egg, soybean, crab and pork may be the most important food varieties should be paid more attention to.

Objective:To observe the effects of berberine on procoagulant and fibrinolytic inhibitory factors produced by rat type Ⅱ alveolar epithelial cell (AECⅡ) induced by lipopolysaccharide (LPS).Methods:AECⅡ cells (RLE-6TN cells) were cultured in vitro, and the cells in logarithmic growth phase were collected. The cytotoxicity text of berberine was detected by cell counting kit-8 (CCK-8) to determine the drug concentration range according to inhibition concentration of half cells (IC 50). The RLE-6TN cells were divided into five groups, the cells in blank control group were cultured in DMEM; the cells in LPS group were stimulated with 5 mg/L LPS; and the cells in berberine pretreatment groups were pretreated with 20, 50 and 80 μmol/L berberine for 1 hour, and then were co-cultured with 5 mg/L LPS. The cells were collected after LPS induced for 24 hours. The protein and mRNA expression levels of tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasminogen activator inhibitor-1 (PAI-1) in the cells were detected by Western blotting and real-time fluorescence quantification reverse transcription-polymerase chain reaction (RT-qPCR). The levels of activated protein C (APC), precollagen Ⅲ peptide (PⅢP), thrombin-antithrombin complex (TAT) and antithrombin Ⅲ (ATⅢ) in the cell supernatant were measured by enzyme linked immunosorbent assay (ELISA). Results:According to the inhibition rate curve, the IC 50 of berberine on RLE-6TN cells was 81.16 μmol/L. Therefore, 20, 50 and 80 μmol/L were selected as the intervention concentration of berberine. Compared with the blank control group, the expression and secretion of procoagulant and fibrinolytic inhibitory factors were abnormal in RLE-6TN cells after LPS induced for 24 hours. The protein and mRNA expression levels of TF and PAI-1 in the LPS group were significantly increased, but the protein and mRNA expression levels of TFPI were significantly decreased. Meanwhile, the levels of APC and ATⅢ in the cell supernatant were significantly decreased, while the levels of PⅢP and TAT were significantly increased. After pretreatment with berberine, the abnormal expression and secretion of procoagulant and fibrinolytic inhibitory factors induced by LPS were corrected in a dose-dependent manner, especially in 80 μmol/L. Compared with the LPS group, the protein and mRNA expression levels of TF and PAI-1 in the berberine 80 μmol/L group were significantly decreased [TF protein (TF/GAPDH): 0.45±0.02 vs. 0.55±0.03, TF mRNA (2 -ΔΔCt): 0.39±0.08 vs. 1.48±0.11, PAI-1 protein (PAI-1/GAPDH): 0.37±0.02 vs. 0.64±0.04, PAI-1 mRNA (2 -ΔΔCt): 1.14±0.29 vs. 4.18±0.44, all P < 0.01] and those of TFPI were significantly increased [TFPI protein (TFPI/GAPDH): 0.53±0.02 vs. 0.45±0.02, TFPI mRNA (2 -ΔΔCt): 0.94±0.08 vs. 0.40±0.05, both P < 0.01]. Meanwhile, the levels of APC and ATⅢ in the cell supernatant were significantly increased [APC (μg/L): 1 358.5±26.0 vs. 994.2±23.1, ATⅢ (μg/L): 118.0±7.4 vs. 84.4±2.7, both P < 0.01], while those of PⅢP and TAT were significantly decreased [PⅢP (μg/L): 11.2±0.4 vs. 18.6±0.9, TAT (ng/L): 222.1±2.8 vs. 287.6±7.0, both P < 0.01]. Conclusions:Berberine could inhibit the LPS-induced expressions of procoagulant and fibrinolytic inhibitory factors in rat AECⅡ cells and promote the expressions of anticoagulant factors in a dose-dependent manner. Berberine may be a new therapeutic target for alveolar hypercoagulability and fibrinolysis inhibition in acute respiratory distress syndrome (ARDS).

Objective:To determine the effect of andrographolide (AD) on the expression of procoagulant and fibrinolytic inhibitory factors in rat type Ⅱ alveolar epithelial cells (AECⅡ) stimulated by lipopolysaccharide (LPS).Methods:The AECⅡ cells RLE-6TN in the logarithmic growth phase were divided into 5 groups: the normal control (NC) group, the LPS group, and the 6.25, 12.5, and 25 mg/L AD groups (AD 6.25 group, AD 12.5 group, AD 25 group). The NC group was cultured with RPMI 1640 conventional medium. In the LPS group, 5 mg/L LPS was added to the RPMI 1640 conventional medium for stimulation. Cells in the AD groups were treated with 6.25, 12.5, and 25 mg/L AD in advance for 1 hour and then given LPS to stimulate the culture. The cells and cell culture supernatant were collected 24 hours after LPS stimulation. The protein and mRNA expressions of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibition-1 (PAI-1) in cells were detected by Western blotting and real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). The levels of procollagen Ⅲ peptide (PⅢP), thrombin-antithrombin complex (TAT), antithrombin Ⅲ (AT-Ⅲ) and activated protein C (APC) in the cell supernatant were detected by enzyme linked immunosorbent assay (ELISA).Results:Compared with the NC group, the protein and mRNA expressions of TF and PAI-1 in the LPS group were significantly increased, and the protein and mRNA expressions of TFPI were significantly reduced. At the same time, the levels of PⅢP and TAT in the cell supernatant were significantly increased, the levels of AT-Ⅲ, APC were significantly reduced. Compared with the LPS group, the protein and mRNA expressions of TF and PAI-1 in AD 6.25 group, AD 12.5 group, AD 25 group were significantly reduced [TF/GAPDH: 0.86±0.08, 0.45±0.04, 0.44±0.04 vs. 1.32±0.10, TF mRNA (2 -ΔΔCt): 2.59±0.25, 2.27±0.05, 1.95±0.04 vs. 4.60±0.26, PAI-1/GAPDH: 2.11±0.07, 1.45±0.04, 0.86±0.09 vs. 2.56±0.09, PAI-1 mRNA (2 -ΔΔCt): 3.50±0.22, 2.23±0.29, 1.84±0.09 vs. 6.60±0.27, all P < 0.05], while the protein and mRNA expressions of TFPI were significantly increased [TFPI/GAPDH: 0.78±0.05, 0.81±0.03, 0.84±0.07 vs. 0.36±0.02, TFPI mRNA (2 -ΔΔCt): 0.46±0.09, 0.69±0.07, 0.91±0.08 vs. 0.44±0.06, all P < 0.05]. Also the levels of PⅢP and TAT in the cell supernatant were significantly reduced, and the levels of AT-Ⅲ and APC were significantly increased [PⅢP (μg/L): 13.59±0.23, 12.66±0.23, 10.59±0.30 vs. 15.82±0.29, TAT (ng/L): 211.57±6.41, 205.69±4.04, 200.56±9.85 vs. 288.67±9.84, AT-Ⅲ (μg/L): 102.95±3.86, 123.92±2.63, 128.67±1.67 vs. 92.93±3.36, APC (μg/L): 1 188.95±14.99, 1 366.12±39.93, 1 451.15±29.69 vs. 1 145.55±21.07, all P < 0.05]. With the increase of the dose of AD, the above-mentioned promotion and inhibition effects became more obvious. In the AD 25 group, TF, PAI-1 protein and mRNA expressions decreased, TFPI mRNA expression increased, PⅢP level in the supernatant decreased and AT-Ⅲ, APC levels increased compared with AD 6.25 group, the difference was statistically significant, and the decrease of PAI-1 protein expression and PⅢP level in the supernatant were also statistically significant compared with AD 12.5 group. Conclusions:Andrographolide in the dose range of 6.25-25 mg/L can dose-dependently inhibit the expression and secretion of procoagulant and fibrinolytic inhibitor-related factors in AECⅡ cells RLE-6TN stimulated by LPS, and promote the secretion of anticoagulant factors. 25 mg/L has the most obvious effect.

Objective:To explore the performance of the commonly used whole blood C-reactive protein (CRP) detection systems and give related recommendation on the performance requirements of detection systems.Methods:A total of 7 540 venous blood samples from 26 maternal, child and children′s hospitals were collected to conduct this multi-center study on the analytical performance of 5 commonly used whole blood CRP detection systems from March to April in 2019. The blank check, carryover, repeatability, intermediate precision, linearity, sample stability, influence of hematocrit/triglyceride/bilirubin, comparison with SIEMENS specific protein analyzer and trueness were evaluated. The 5 systems included BC-5390CRP autohematology analyzer, AstepPLUS specific protein analyzer, Ottoman-1000 Automated Specific Protein POCT Workstation, i-CHROMA Immunofluorometer equipment Reader and Orion QuikRead go detecting instrument. The 5 systems were labeled as a, b, c, d and e randomly.Results:Within the 5 systems, all values of blank check were less than 1.00 mg/L, the carryovers were lower than 1.00%. The repeatability of different ranges of CRP concentrations including 3.00-10.00, 10.00-30.00 and>30.00 mg/L were less than 10.00%, 6.00% and 5.00%, respectively, and the intermediate precision was less than 10.00%. The linearity correlation coefficients of the 5 systems were all above 0.975, while the slope was within 0.950-1.050. Whole blood samples were stable within 72 hours both at room temperature (18-25 ℃) and refrigerated temperature (2-8 ℃). The CRP results were rarely influenced by high triglyceride or bilirubin, except for the immmunoturbidimetric test based on microparticles coated with anti-human CRP F(ab) 2 fragments. When triglyceride was less than 15.46 mmol/L, the deviation of CRP was less than 10.00%. When bilirubin was less than 345.47 μmol/L, the deviation of CRP was less than 10.00%. CRP was more susceptible to Hct on the systems without Hct correction. The deviation of CRP between different Hct dilution concentration and 40% dilution concentration can reach as high as 67.48%. The correlation coefficients ( r) of 5 systems were all more than 0.975 in the range of 0-300.00 mg/L compared with Siemens specific protein analyzer. All systems passed the trueness verification using the samples with specified values of 12.89 and 30.60 mg/L. Conclusion:The performance of 5 systems can basically meet the clinical needs, but it is suggested that the whole blood CRP detection system without automatic Hct correction should be modified manually.

Objective:To explore the effect of small dose of low molecular weight heparin on the prognosis of elderly patients with severe pneumonia using systematic evaluation method.Methods:Databases including Wanfang data, VIP, CNKI, SinoMed, PubMed, Embase and Cochrane Library were searched for randomized controlled trial (RCT) studies about the comparison of conventional therapy and low molecular weight heparin on prognosis of elderly patients with severe pneumonia from the time of database establishment to August 2019. The patients in conventional treatment group were treated by improving ventilation, anti-infection, eliminating phlegm, relieving asthma and maintaining homeostasis while those in low molecular weight heparin group were subcutaneously injected with low molecular weight heparin of 4 000 U, once a day for 7 days. The patients' main outcomes included the oxygenation index (PaO 2/FiO 2) after 7 days of treatment, duration of mechanical ventilation, mortality in hospital, and secondary outcomes included acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and coagulation function after 7 days of treatment, the length of intensive care unit (ICU) stay, and incidence of bleeding. Data extraction and quality evaluation were conducted. The Meta-analysis of included studies that met the quality standards was performed using RevMan 5.3 software. Funnel diagram analysis was used to analyze the parameters with no less than 10 studies enrolled. Results:A total of 14 RCT studies were enrolled involving 1 173 elderly patients with severe pneumonia, among whom 590 received low molecular weight heparin while the other 583 received conventional therapy. All the included studies were well designed and of high quality. The results of Meta-analysis showed that compared with conventional therapy, small dose of low molecular weight heparin significantly elevated PaO 2/FiO 2 after 7 days of treatment [mean difference ( MD) = 19.25, 95% confidence interval (95% CI) was 16.88 to 21.61, P < 0.000 01], shortened the duration of mechanical ventilation ( MD = -48.88, 95% CI was -67.42 to -30.33, P < 0.000 01), and decreased mortality in hospital [odds ratio ( OR) = 0.40, 95% CI was 0.22 to 0.73, P = 0.003] and APACHEⅡ score after 7 days of treatment ( MD = -3.38, 95% CI was -3.94 to -2.83, P < 0.000 01), and shortened the length of ICU stay ( MD = -4.51, 95% CI was -5.75 to -3.27, P < 0.000 01). There was no significant difference in the changes of coagulation parameters after 7 days of treatment or the incidence of bleeding between low molecular weight heparin group and conventional therapy group [7-day thrombin time (TT): MD = 0.57, 95% CI was -0.15 to 1.28, P = 0.12; 7-day prothrombin time (PT): MD = 0.32, 95% CI was -0.35 to 0.98, P = 0.35; 7-day fibrinogen (FIB): MD = -0.17, 95% CI was -0.45 to 0.10, P = 0.22; incidence of bleeding: OR = 0.86, 95% CI was 0.36 to 2.07, P = 0.74]. The funnel diagram showed that there was publication bias of included 10 studies about APACHEⅡ score after 7 days of treatment. Conclusion:Small dose of low molecular weight heparin can improve the prognosis of elderly patients with severe pneumonia and it has no obvious side-effect on coagulation function.