BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective : To investigate the association between single nucleotide polymorphism(SNP) of PROS1 gene and recurrent spontaneous abortion(RSA) in Baotou Han population. Methods : 158 RSA patients and 158 control subjects were selected as the study subjects, and the activities of protein S, protein C and antithrombin-Ⅲ were measured. The rs13062355, rs6441600 and rs12634349 loci of PROS1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Non-conditional Logistic regression was used to analyze the correlation between three SNPs of PROS1 gene and the risk of RSA. Results : The protein S and antithrombin-Ⅲ activities of RSA patients decreased significantly(P<0.05). PROS1 SNP rs13062355 was associated with the risk of RSA under the dominant model: compared with genotype TT, patients with CT+CC genotypes had a reduced risk of RSA(OR=0.398, 95%CI: 0.249-0.638); SNP rs6441600 and rs12634349 were not associated with the risk of RSA(P>0.05). In the haplotypes constructed by PROS1 rs13062355, rs6441600 and rs12634349, Haplotype C-C-C was statistically different between the two groups(P<0.05). The third-order interaction model rs13062355-rs6441600-rs12634349 was associated with the risk of RSA. Conclusion PROS1 SNP rs13062355 may be associated with the risk of RSA in Han women in Baotou area. Haplotype C-C-C of PROS1 rs13062355, rs6441600 and rs12634349 reduces the risk of RSA. The third-order model rs13062355-rs6441600-rs12634349 interaction has a synergistic effect on the occurrence of RSA.

Objective To explore the prevalence of 9 respiratory pathogens from March 2023 to February 2024,as well as the detection efficiency of various methods for pathogens.Methods A retrospective analysis was conducted on the detection of 9 pathogens in 38 948 patients who first presented with respiratory symp-toms from March 2023 to February 2024,as well as the detection efficacy of nucleic acid,antigen,antibody and other methods.Results Firstly,among 38 948 patients,a total of 8 345 cases(21.43%)were detected with at least one pathogen,of which 8 158 cases(20.95%)were detected with only one pathogen,and 187 cases(2.29%,187/8 158)were detected with two or more pathogens.The top three detection rates were SARS-CoV-2(20.37%),mycoplasma pneumoniae(MP,15.58%)and influenza A virus(IVA,10.79%).Secondly,among patients who detected at least one of the nine pathogens,the detection rate was 24.94%in autumn,21.45%in spring,18.54%in summer,and 19.22%in winter,and the difference in detection rates between the four seasons was statistically significant(P<0.001).Thirdly,except for the relatively high detection rates of SARS-CoV-2 in spring(51.24%)and summer(37.31%),and the highest detection rate of IVB in winter(11.28%),the detection rates of other pathogens were highest in autumn.Fourthly,there was a statistically significant difference in the total detection rates among the children group(31.83%),the youth group(12.48%),the middle-aged group(10.70%),and the elderly group(12.43%)(P<0.001).The detection rates of 7 pathogens,including MP,IVA,Influenza B virus(IVB),syncytial virus,CP,adenovirus,and parain-fluenza virus type 1,were highest in children,and there was a statistically significant difference in comparison between different age groups(P<0.05).The detection rate of SARS-CoV-2 in the children group(3.45%)was lower than that in other age groups(30.90%,29.09%,32.16%,P<0.001).There was no statistically significant difference in HPIV-3 between different age groups(P=0.478).Fifthly,there was no significant difference in overall detection rate between male and female(P>0.05).However,the detection rates of MP and CP in female were higher than those in male(P<0.05),while IVA in male was slightly higher than that in female(P=0.014).There were no significant differences in the detection rate of other 6 pathogens between female and male(P>0.05).Sixthly,the detection rate of MP antigen was lower than that of MP nucleic acid detection(P<0.001),and the detection rate of MP antibody detection was lower than that of MP nucleic acid detection(P<0.001).The detection rate of MP antibody detection increased significantly with the extension of time from initial symptoms to medical treatment(P<0.001).Seventhly,the detection rates of antigen of IVA,IVB,RSV and ADV were significantly lower than those of the corresponding nucleic acid(P<0.001),and the detection rates of nucleic acid testing for 4 kinds of pathogen was about 5 times that of the correspond-ing antigen testing(4.75-6.25 times).And the consistency of the detection rate between antigen detection and nucleic acid detection was poor(Kappa=0.046-0.239).Conclusion The prevalence of common respir-atory pathogens from March 2023 to February 2024 exhibits certain characteristics.Moreover,the detection ef-ficiency of different methods for pathogens varies greatly,and appropriate detection methods should be select-ed based on a thorough understanding of their performance.

Objective To explore the acceptability of routine biochemical test results for serum samples with varying degrees of chylous high triglyceride(TG).Methods Blood samples of 69 patients with different degrees of lipids were collected,including 33 patients with mild to moderate lipids(1.7 mmol/L≤TG<5.6 mmol/L)and 36 patients with severe lipids(TG≥5.6 mmol/L).Twenty-nine biochemical tests were detected before and after high-speed centrifugation.The result acceptability before high speed centrifugation of serum was compared with the results after high speed centrifugation as the gold standard[TG and total cholesterol(TC)before centrifugation].The acceptable criteria were subject to the following three conditions at the same time.Firstly,correlation coefficient(R2)was greater than or equal to 0.95.Secondly,the slope of linear re-gression equation was 1.00±0.05.Thirdly,for the same index,the number of samples whose result bias be-fore and after centrifugation was less than 1/2 total allowable error(TEa)in more than 90%of the total sam-ple numbers.Results Firstly,in the mild to moderate lipemia group,22 tests met the criteria,7 tests did not,including total protein(TP),albumin(ALB),TG,aspartate aminotransferase(AST),carbon dioxide(CO2),α-L-fucosidase(AFU),lactate dehydrogenase(LDH)(bias<10%),and the coincidence rate was 75.9%.In the severe lipemia group,12 tests met the criteria,17 tests did not,including pre-albumin(PA),AFU,γ-glu-tamyltransferase(γ-GT),LDH,AST,TC,direct bilirubin(DBIL),CO2,5'-nucleotidase(5'-NT),small and low-density lipoprotein cholesterol(sd-LDL-C),high density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),adenosine deaminase(ADA),cystatin C(CysC),glycosylated albumin(GA),total bilirubin(TBIL)(bias>10%),the coincidence rate was 41.4%,and there was a statistically sig-nificant difference in the coincidence rate between the two groups(P<0.05).Secondly,there was no statisti-cally significant difference in the acceptability of results between continuous monitoring method and endpoint method detection methods(P>0.05).Conclusion Most test results of direct determination with mild or moderate lipemia samples are acceptable,and the bias of unacceptable tests is small(<10%),so it is recom-mended to issue a test report without further sample treatment.However,due to the large number of unacceptable tests and larger bias(>10%),severe lipemia samples should be determined after high-speed centrifugation.

Rolling manipulation is one of the swing techniques with strong operational skills in massage therapy. This article summarized the biomechanical parameters and mechanism of the massage operation from multiple perspectives, including three-dimensional motion, force trajectory, dynamic parameters, force effect relationship, and mechanism. It is found that the massage operation could exert force in the vertical and horizontal directions of the body surface, and the movement trajectories of the front and back were generally symmetrical. The anterior force was approximately three times the retraction force, and the brachioradialis, pectoralis major, triceps, and deltoids were the main muscles that could exert force during manual manipulation. The method can have effects on hemodynamics, cellular anti-inflammatory effects, and improve the physiological function of tissues and organs. However, there is currently a lack of objective and unified norms and standards for the specific strength, frequency, and specific parameter combinations of massage methods, so the further improvement is still needed.

Centrifugal blood pumps drive blood flow by regulating blood flow rate,and have been widely used in clinical applications,including extracorporeal membrane oxygenation(ECMO),cardiopulmonary bypass(CPB),and extracorporeal circulation carbon dioxide removal(ECCO2R).However,because different structures and different forms of centrifugal pumps have different requirements for blood extracorporeal circulation in clinical application scenarios,blood pumps face different application conditions in clinical use.In this study,the effects of different structures of centrifugal pumps and different working conditions on blood damage are summarized for reference by relevant institutions and R&D personnel.

Objective To compare the clinical effects of minimally invasive percutaneous plate osteosynthesis (MIPO) and minimally invasive intramedullary nailing osteosynthesis (MINO) in the treatment of humeral shaft fractures. Methods The clinical data of 53 patients with humeral shaft fractures treated with MIPO and MINO were retrospectively analyzed. The patients were divided into MIPO group of 25 patients and MINO group of 28 patients according to differed surgical approaches. The operation time, blood loss, length of hospital stay, fracture healing time, University of California at Los Angeles (UCLA) shoulder function score at 1 year postoperatively, and Mayo elbow performance score at 1 year postoperatively were compared between the two groups. Results All 53 patients successfully completed the surgery, and no postoperative complications such as surgical site infection, radial nerve injury, fracture nonunion, implant breakage, or loosening occurred. There were no statistically significant differences between the two groups in terms of operation time, blood loss, length of hospital stay, fracture healing time, and Mayo elbow performance score at 1 year postoperatively (P>0.05). The UCLA shoulder function score at 1 year postoperatively was better in the MIPO group than in the MINO group (P < 0.05). One patient in the MIPO group experienced wound fat liquefaction, and one patient in the MINO group experienced radial nerve palsy. Conclusion Both MIPO and MINO can achieve satisfactory results in the treatment of humeral shaft fractures, and both minimally invasive techniques are worthy of clinical promotion. However, MIPO has lesser impact on shoulder function.

Objective To investigate the effect of aqueous extract of Scrophularia ningpoensis(AESN)on AMP-activated protein kinase(AMPK)activity in INS-1 cells under high glucose(HG)conditions.Methods INS-1 cells were cultured in HG medium and treated with different concentrations of AESN.The influences of AESN on cell viability and pyroptotic body formation were detected using the CCK-8 assay.Western blotting was used to observe the effects of AESN on AMPK expression and phosphorylation.The effect of AESN on AMPK activity was measured using time-resolved fluorescence resonance energy transfer(TR-FRET)assay.Results Compared with normal glucose controls,INS-1 cells exposed to HG showed decreased cell viabilities and increased formation of pyroptotic bubbles using CCK-8 assay.Western blotting results indicated that HG exposure led to a decrease in intracellular AMPK phosphorylation levels.However,co-incubation with AESN under HG exposure AESN treatment increased the cell viabilities and phosphorylation of AMPK and decreased the pyroptotic bubbles formation in a concentration-dependent manner.In addition,the results of TR-FRET revealed that AESN treatment effectively increased AMPK activity in a concentration-dependent manner.Conclusion AESN has an activating effect on AMPK activity in HG-treated INS-1 cells.

Objective To investigate the effects of acute sleep deprivation on the behavior and synaptic protein expression of rats.Methods Seventy healthy male Wistar rats were randomly divided into seven groups,a Control group and sleep deprivation groups(24,48,72,96,120 and 144 hours).The sleep deprivation rat model was established by the modified multiplatform water environment sleep deprivation method.Spatial learning and memory were assessed by the Morris water maze.Anxiety was assessed by the open field test.The morphology and quantity of hippocampal neurons were observed by Nissl staining.Western blot and Real-time PCR were used to determine the expression of synaptophysin(SYN),post-synaptic density protein-95(PSD-95),and brain-derived neurotrophic factor(BDNF)in rats.Results Compared with the Control group,the numbers of standing and modification were significantly increased by prolongation of the sleep deprivation time(P＜0.05).The escape latency and path length were significantly increased in 120 and 144 h groups(P＜0.05),whereas the number of platform crossings and the percentage of the target quadrant time were significantly decreased(P＜0.01)and negatively correlated to the sleep deprivation time.The expression levels of BDNF,SYN,and PSD-95 were significantly decreased with the prolongation of sleep deprivation time(P＜0.01).Conclusions With the increase in sleep deprivation time,cognitive dysfunction and anxiety gradually deteriorated,which may be related to decreases in the expression of synaptic biomarkers.

Objective To investigate the performance of different methods in common autoantibody detec-tion,and to provide basis for the detection strategy of autoantibody.Methods A total of 2 657 cases were in-cluded in this study,whose serum antinuclear antibody(ANA)by indirect immunofluorescence method(IIF)and antinuclear antibody spectrum(ANAs,a total of 15 antibodies)by immunoblot method(IB)were tested simultaneously,and anti-double strand DNA antibody(anti-dsDNA antibody)were tested by IIF,enzyme linked immunosorbent assay(ELISA)and IB.ANCA and ANCA spectrum[anti-myeloperoxidase antibody(anti-MPO antibody),anti-protease 3 antibody(anti-PR3 antibody)]were tested by IIF and ELISA respec-tively in 2 348 cases.Results Firstly,the detection rate of ANA was significantly higher than that of ANAs(57.77％vs.30.64％,P＜0.001).Among the specimens detected with ANA,40.78％detected at least one specific antibody positive.Among the specimens detected with ANAs positive,ANA was not detected in 23.10％of cases.Secondly,the ANA positive cases were mainly of lower titers,and cases with titer of ≤1∶320 accounted for 84.95％of the total detected cases.But the higher the titer,the higher the detection rate of ANAs specific antibodies(29.63％in 1∶100,48.56％in 1∶320,77.78％in 1∶1 000,92.42％in≥1∶3 200).Thirdly,among the specimens detected ANAs positive,the composition ratios of anti-Scl-70,anti-PM-Scl and anti-PCNA antibodies in ANA positive cases was significantly lower than those in ANA negative cases(P＜0.001).Fourthly,the detection rate of anti-dsDNA antibody by ELISA was the highest(4.14％),which was significantly higher than those by IIF or IB(both P＜0.001),and the difference in detection efficacy of the latter two methods was also statistically significant(P＜0.001).Even so,the IIF and IB for the detection of anti-dsDNA antibody still had a certain complementary effect on ELISA.Fifthly,the positive rate of ANCA by IIF was significantly higher than that of ANCA spectrum(9.16％vs.2.43％),but among those who were detected anti-MPO antibodies and/or anti-PR3 antibodies positive,47.37％were ANCA negative.Conclusion Different methods for detecting autoantibodies have significantly different detection efficacy,and it is partic-ularly necessary to adopt correct detection strategies based on evidence-based medicine.