Background and objective Pembrolizumab(PEM)has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer(NSCLC),but clinical trials were based on cohorts of patients selected on specific criteria,and whether the findings are consistent with real-world patients is debatable.The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.Methods A retro-spective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted.Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy.Results Among 450 matched patients,the incidence rates of any-grade adverse events were 79.87％in the PEM group and86.71％inthe chemotherapy group,while the incidence rates of grade＞3 adverse events were 4.03％and 7.31％,respectively.The objective response rates were 48.63％for PEM and 36.00％for chemotherapy(P=0.011).The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy(P＜0.001),and the median overall survival was not reached for PEM and 26.2 months for chemotherapy(P＜0.001).Conclusion PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Objective To propose a distribution feature extraction algorithm based on wavelet packet coefficients to reconstruct the signal energy sequence for effectively identifying the pathological features of heart sounds,thereby realizing the early screening of heart diseases.Methods The original heart sound signal was decomposed into 10 layers using wavelet packet decomposition algorithm.After obtaining the wavelet packet coefficients of each layer,each coefficient was reconstructed,and the energy of the reconstructed signal was calculated and arranged in the original order to form the energy sequence.The distribution characteristics of the energy sequence of the reconstructed signals at each layer were analyzed,and distribution features were taken as classification features.Support vector machine,K-nearest neighbor,and decision tree were used to classify and recognize normal heart sounds and the heart sound signals of various diseases.Results The combination of the distribution features of the reconstructed signal energy sequence and decision tree classifier had an accuracy of 93.6%for classifying 5 types of heart sounds on the public dataset,and the accuracy was 95.6%for identifying normal heart sounds and hypertrophic cardiomyopathy heart sounds.Conclusion The proposed algorithm can extract the effective pathological information of abnormal heart sounds,providing a reference for clinical cardiac auscultation.

OBJECTIVE: To provide evidence for further reducing the incidence of central line-associated bloodstream infection (CLABSI) according to investigation of the prevention and control of CLABSI in intensive care unit (ICU) in Shandong Province. METHODS: The questionnaire was developed by experts from Shandong Critical Care Medical Quality Control Center, combining domestic and foreign guidelines, consensus and research. A convenient sampling method was used to recruit survey subjects online from October 11 to 31, 2023 in the province to investigate the management status of central venous catheter (CVC) in ICU units of secondary and above hospitals. RESULTS: A total of 201 valid data were collected, involving 186 hospitals in the province, with a total of 201 ICU units, mainly comprehensive ICU (91%). The beds in ICU units were mainly single rooms (89%) and triple rooms (79%), and the ratio of doctors to total beds was 0.54 : 1. The training on the knowledge and operation of intravascular catheter-associated bloodstream infection in each ICU unit was mainly irregular (49%), and 96% of the catheter operators were authorized by the hospital. In terms of CVC selection, 89% of ICU units used dual-chamber CVC, and 86% of ICU units used catheters without antibiotic coating. When selecting the placement site, for conventional CVC catheterization, 65% preferred subclavian vein. Femoral vein was preferred in 87% of ICU units undergoing continuous renal replacement therapy. 95% of ICU units had established standardized operation procedure (SOP) for CVC placement. 86% of ICU units were capable of ultrasound positioning or guided puncture at the time of catheterization. During catheterization, 88% of ICU units met the sterile dress code. Before and after catheterzation, 81% and 77% of ICU units standardized hand hygiene. Only 31% of ICU units were covered from head to toe by aseptic wipes. For the choice of skin disinfectant, the majority of ICU units (72%) only used iodophor. After tube placement, 54% of ICU units chose sterile transparent dressing and 25% chose sterile gauze dressing. 98% of ICU units were sutured to secure the catheter. Regarding catheter replacement and removal, 45% of ICU units could not be removed or replaced within 2 days in emergency situations where the principle of sterility was not guaranteed. When CLABSI was suspected, 55% of ICU units were able to obtain the catheter tip, transcatheter blood culture, and contralateral peripheral vein blood culture at the same time. For CVC replacement frequency, most ICU units (75%) would not be replaced regularly, and some ICU units would be replaced regularly, but the frequency of replacement was different. For CLABSI prevention and control, 82% of ICU units developed a verification form or supervision form. When analyzing the sources of CLABSI data, most of them were filled in by themselves (60%). As for the frequency of data analysis, 57% were once a month. CONCLUSIONS All ICU units in Shandong Province are standardized in terms of the authorization of operators, the formulation of SOP, the formulation and implementation of verification form and supervision form, ultrasound-guided puncture, and hand hygiene before and after catheterization. However, there are still deficiencies in the training on knowledge and operation of intravascular catheter-associated bloodstream infections, maximum aseptic coverage, catheter replacement and removal, and the reporting sources of CLABSI data, which need to be strengthened in the follow-up work. At present, the selection of CVC, the selection of catheterization site, the selection of skin disinfectant and the selection of dressings after catheterization still need further research.
Intensive Care Units ; Humans ; Surveys and Questionnaires ; China/epidemiology* ; Cross-Sectional Studies ; Catheter-Related Infections/epidemiology* ; Catheterization, Central Venous/methods* ; Cross Infection/epidemiology* ; Central Venous Catheters/adverse effects* ; Infection Control/methods*

A-kinase anchor protein 12 (AKAP12) is a scaffold protein that improves the specificity and efficiency of spatio-temporal signals by assembling intracellular signal proteins into specific complexes. In recent years, the role of AKAP12 in chronic liver diseases has attracted more and more attention. This article introduces the physiological functions of AKAP12 and reviews the role of AKAP12 in chronic liver diseases, in order to lay a foundation for the use of AKAP12 small molecule as a new therapeutic target for chronic liver diseases.

Objective:To analyze the application and funding status of various projects of nuclear medicine and molecular imaging supported by the National Natural Science Foundation of China (NSFC) from 2013 to 2022, and explore the challenges faced by basic research and clinical transformation in this field.Methods:From 2013 to 2022, application and funding information of nuclear medicine and molecular imaging projects (secondary code H2704, H2706) from five departments of Medical Science Department of NSFC were retrospectively collected. The number of applications, number of funding, funding direction, funding intensity, distribution of supporting units and research hotspots of various projects in this field were analyzed.Results:From 2013 to 2022, the total number of applications of various projects in the field of nuclear medicine and molecular imaging reached 5 387, and the total number of grants reached 899. The number of applications and grants showed a steady growth trend. The overall funding intensity increased from 48.935 0 million yuan in 2013 to 59.495 4 million yuan in 2022, with the increase of 21.58%. Among all supporting units, Shanghai Jiao Tong University topped the list for both the number of applications (440) and the number of grants (82), Xiamen University ranked the first in terms of overall funding rate (25.42%, 30/118), and Peking University ranked the first in terms of total funding intensity (41.897 1 million yuan). Research hotspots focused on the construction of tumor targeted molecular probes and precise imaging of tumor internal molecular components.Conclusion:In the past decade, the number of related projects and total funding of nuclear medicine and molecular imaging supported by NSFC have steadily increased, and the types of funded projects are diverse and interdisciplinary, promoting the innovative development of nuclear medicine and molecular imaging disciplines in China.

Liver fibrosis (LF) is a pathological process of hepatic stellate cell (HSC) activation and excessive deposition of extracellular matrix caused by chronic liver injury and inflammation. HSC activation is the core mechanism of LF, and inhibiting HSC activation is the key to promoting the reversal of LF. In recent years, rapid development has been achieved for the application of nanomedicine targeting HSC in the treatment of LF. This article mainly introduces nanomedicine, the mechanism of action of nanomedicine in the treatment of LF, and potential targets, and it is pointed out that nanomedicine may become a new method for the treatment of LF.

Aerospace Medicine ; Aviation ; China ; Dermatitis ; Humans ; Medicine

C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.
Animals ; Apoptosis ; Carcinoma, Squamous Cell ; Cell Line, Tumor ; Down-Regulation ; Endoplasmic Reticulum Stress ; Head and Neck Neoplasms ; Mice ; Mouth Neoplasms ; Oxidoreductases

Objective:To explore the effect of Vancomycin on immune hemolysis and coagulation in children with non-Hodgkin′s lymphoma (NHL), thus providing the basis for the diagnosis and treatment of hemolytic anemia and coagulation dysfunction caused by Vancomycin, and guiding the rational use of drugs in children with NHL.Methods:From January 2018 to January 2019, 31 children with NHL treated with monotherapy of Vancomycin in Beijing Children′s Hospital, Capital Medical University were collected.Plasma samples within 1 week of Vancomycin medication were collected for detecting the anti-Vancomycin antibody by microcolumn gel method.The laboratory diagnostic and coagulation function indexes of hemolytic anemia before and after Vancomycin medication were analyzed using the paired sample t test. Results:Fourteen out of 31 children with NHL were positive for the anti-Vancomycin antibody, and among them, 10 cases had positive direct antiglobulin test (DAT). In NHL children with positive anti-Vancomycin antibody, their red blood cell count (RBC)[(2.75±0.07)×10 12/L vs.(3.18±0.07)×10 12/L], platelet count (PLT)[64.29±14.87)×10 9/L vs.(91.36±16.84)×10 9/L] and hematocrit (HCT)[(23.02±0.83)% vs.(29.19±1.98)%] were significantly reduced after Vancomycin medication than those before treatment (all P<0.01). On the contrary, total bilirubin (TB) [(51.96±15.52) μmol/L vs.(39.34±13.40) μmol/L], direct bilirubin (DB)[(31.30±13.98) μmol/L vs.(26.38±12.61) μmol/L], indirect bilirubin (IB)[(21.81±2.89) μmol/L vs.(13.75±1.63) μmol/L] and lactate dehydrogenase (LDH)[(208.6±16.85) U/L vs.(60.93±16.00) U/L] in them were significantly enhanced after Vancomycin medication than those before treatment (all P<0.05). Prothrombin time (PT)[(13.94±0.58) s vs.(11.66±0.30) s] and partial thromboplastin time (APTT)[(36.01±2.64) s vs.(28.09±0.98) s] were significantly prolonged in them after vancomycin medication than those before treatment (all P<0.01). A higher international normalized ratio (INR)(1.25±0.05 vs.1.05±0.02) was detected in NHL children with positive anti-Vancomycin antibody after medication ( P<0.000 1). In NHL children with negative anti-Vancomycin antibody, significantly higher PT (12.99±0.35) s vs.(11.82±0.27) s and INR (1.18±0.03 vs.1.07±0.03) were detected after Vancomycin medication (all P<0.000 1), while other indexes were similar before and after treatment. Conclusions:The anti-Vancomycin antibody may cause immune hemolysis and coagulation dysfunction in children with NHL.In order to prevent serious adverse events caused by drug antibodies, comprehensively clinical symptoms should be considered, drug antibodies and laboratory test results should be detected.

Objective:To compare the detection rate of genital Chlamydia trachomatis (CT) DNA between urine and urethral/cervical swab samples. Methods:From December 2018 to December 2019, a total of 1 475 outpatients were collected from sexually transmitted disease clinics in 7 medical institutions, such as Department of Venereology, Guangzhou Institute of Dermatology, including 1 118 males and 357 females. One urethral/cervical swab sample and one urine sample were collected successively from each patient. Real-time fluorescence-based PCR was performed to detect CT DNA in urine and urethral/cervical swab samples, and paired chi-square test was used to compare the positive rate of CT DNA between the 2 kinds of samples. Random- or fixed-effect meta-analysis was conducted for the test of heterogeneity and merging of positive rates of CT DNA in the urine and urethral/cervical swabs among 7 medical institutions.Results:The positive rate of CT DNA in the urine samples was significantly higher than that in the swab samples from 4 medical institutions (all P < 0.05) , while there was no significant difference in the positive rate of CT DNA between the 2 kinds of samples from 3 medical institutions (all P > 0.05) . The heterogeneity ( I2) estimates of the CT-DNA positive rate in urine and swab samples among different medical institutions were 78.6% (95% CI: 55.9% - 89.6%) and 73.7% (95% CI: 43.7% - 87.7%) , respectively; meta-analysis showed that the total merged positive rate of CT DNA in the urine samples was 10.8% (95% CI: 7.2% - 15.9%) , which was significantly higher than that in the swab samples (7.8%, 95% CI: 4.9% - 12.1%; χ2 = 39.2, P < 0.05) . Compared with the swab sample-based CT-DNA detection method, the sensitivity, specificity, positive predictive value, negative predictive value and consistency rate of the urine sample-based CT-DNA detection method were 97.0% (128/132) , 96.3% (1 293/1 343) , 71.9% (128/178) , 99.7% (1 293/1 297) , and 96.3% (1 421/1 475) , respectively. The positive rate of CT DNA in the urine samples from 1 118 male patients was 11.0% (95% CI: 7.2% - 16.5%) , which was significantly higher than that in the swab samples (7.6%, 95% CI: 4.9% - 11.8%; χ2 = 34.3, P < 0.05) . There was no significant difference in the positive rate of CT DNA between the urine (11.9%, 95% CI: 7.7% - 17.9%) and cervical swab samples from 357 female patients (10.4%, 95% CI: 7.6% - 14.0%; χ2 = 3.2, P > 0.05) . Conclusions:The positive rate of CT DNA in urine samples is higher than or similar to that in urethral/cervical swab samples. The urine sample-based CT-DNA detection method has characteristics of convenience, non-invasiveness, painlessness and low cost, and is worthy of clinical promotion.