Objective To compare the anesthetic effect and safety of remimazolam and propofol on patients underwent video-assisted thoracoscopic surgery for lung cancer.Methods Clinical data of patients with lung cancer underwent video-assisted thoracoscopic surgery were retrospectively collected.Remimazolam group was anesthetized by remimazolam,and propofol group was anesthetized by propofol.The changes in mean arterial pressure(MAP)and heart rate(HR)were compared between the two groups of patients before anesthesia induction(T0),after 5 min of tracheal intubation(T1),after 1 h of surgery(T2),during thorax closure(T3)and at 5 min after extubation(T4).The sedation onset time,recovery time and extubation time in the two groups were recorded.Stress response indicators[adrenocorticotropic hormone(ACTH),cortisol(Cor)]were compared at T0 and T4.Ramsay sedation score(RSS)was used to assess the sedation degree at T4.Visual analogue score(VAS)was applied to evaluate the pain degree at 2,12 and 24 h after surgery,and the perioperative anaesthesia-related adverse events were observed.Results There were 58 cases in remimazolam group and 64 cases in propofol group.The MAP values at T1 in remimazolam group and propofol group were(85.03±4.37)and(78.24±4.48)mmHg;at T2 were(80.39±3.95)and(75.49±4.11)mmHg;at T3 were(84.43±4.02)and(79.59±3.97)mmHg;the HR values at T2 were(76.44±5.75)and(72.39±6.03)beat·min-1,the difference were all significant(all P＜0.05).The sedation onset times in remimazolam group and propofol group were(62.45±6.27)and(72.33±7.19)s;the recovery times were(7.22±1.23)and(8.24±1.48)min;the extubation times were(8.34±1.50)and(10.09±1.83)min;the RSS scores at T4 were(2.03±0.39)and(1.88±0.35)points,the difference were all significant(all P＜0.05).The total incidence rates of anesthesia-related adverse events in remimazolam group and propofol group were 6.90％and 21.88％,respectively(P＜0.05).Conclusion Both remimazolam and propofol can play a good sedative effect during lung cancer video-assisted thoracoscopic surgery anesthesia.Remimazolam anesthesia has more stable intraoperative hemodynamics,faster onset and elimination,and higher safety.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

ObjectiveGlutathione (γ-glutamyl-L-cysteinylglycine, GSH) is the most abundant non-protein compound containing sulfhydryl (―SH) groups in cells. It serves as a source of reducing equivalents, effectively neutralizing harmful reactive substances, and playing a crucial role in maintaining cellular redox balance. Therefore, sensitive detection and accurate measurement of GSH levels in tissues are of great importance. In this work, we presents a novel method for GSH detection utilizing electron paramagnetic resonance (EPR) spectroscopy. MethodsInitially, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate acid)) solution was mixed with K₂S₂O₈ solution and reacted in the dark for 12 to 16 h to prepare ABTS·⁺ solution, which was then quantified using UV-Vis spectroscopy. Subsequently, the concentration of glutathione (GSH) was determined based on the changes in the EPR signal of ABTS·⁺. On this basis, the optimal reaction time and temperature were explored to establish a standard equation correlating the EPR signal intensity of ABTS·⁺ with GSH concentration. Finally, the derived standard curve was employed to quantitatively analyze the GSH concentration in whole blood from C57BL/6J mice, and the results were compared with those reported in the literature to verify the accuracy of the method. ResultsThe experimental results demonstrate that this method has a linear detection range from50 nmol/L to 15 μmol/L for GSH, spanning two orders of magnitude, with a limit of detection (LOD) at0.50 nmol/L. The measured GSH content in mouse whole blood is (10 660±706) nmol/g Hb, which agrees with the value of (11 200±237) nmol/g Hb as previously reported. Furthermore, a similar method was developed for detection of glutathione disulfide (GSSG) at higher reaction temperature. ConclusionThis article presents a novel assay for the rapid detection of GSH using the intensity of EPR signal from ABTS·⁺ as indicator. This method demonstrates enhanced detection sensitivity and a broader linear range compared to conventional colorimetric methods. Furthermore, we have extended the application of this method to detect GSH content in blood samples efficiently and accurately, offering valuable information for assessing tissue redox balance, thus holding significant potentials.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

In this study,the immunological characteristics of the PhoP protein were explored with a two-component system of Mycobacterium tuberculosis(Mtb).Bioinformatics was used to predict the B and T cell epitopes of the PhoP protein.A re-combinant expression plasmid was constructed by PCR analysis of the phoP sequence and cloning into the prokaryotic expres-sion vector pET-28a(+).Competent Escherichia coli BL21 cells were transformed with the recombinant plasmid and expres-sion was induced with IPTG.The recombinant PhoP protein was purified by affinity chromatography.Serum levels of PhoP-specific antibodies in Mtb-infected mice and tuberculosis(TB)patients were analyzed with an ELISA.BALB/c mice were im-munized with the PhoP recombinant protein by intramuscular injection.Sera of mice were collected and antibody titers were detected with an ELISA and specificity was assessed by West-ern blot analysis.Mouse splenocytes were isolated and the pro-portions of IFN-y-positive cells and cytokine levels were detec-ted with an ELISpot and ELISA,respectively.Bioinformatics i-dentified 24 B cell and 11 T cell epitopes of the PhoP protein.A prokaryotic recombinant vector of PhoP was successfully con-structed and the recombinant PhoP protein was obtained by purification.Specific antibody levels to PhoP in sera of Mtb in-fected mice and TB patients increased significantly,with preci-sion of 99.9％and 82.5％,and specificity of 100％,respectively.PhoP protein immunization successfully induced production of specific antibodies in mice.Stimulated by antigens in vitro,IL-2 and IFN-γ levels were significantly increased in the splenocytes of immunized mice.Immunization with the PhoP protein induce a humoral immune response and Thl-dominated cellular immu-nity,indicating that the PhoP protein was immunogenic with diagnostic efficacy for TB.These results lay a foundation to clari-fy the role of PhoP in Mtb infection and application for diagnosis and prevention of TB.

Objective:To investigate and assess hemolytic transfusion reaction in patient with complex and combined anti-Fya and anti-Jkb which so as to provide a safety blood transfusion strategy.Methods:ABO/Rh blood grouping,antibody screening and identification,and Coombs'tests were performed by the routine serological methods include manual tube and automatic blood group analyzer with matching micro-column gel cards from Diagnostic Grifols and Jiangsu LIBO.The hospital information system and laboratory information system were used to collect dada on patients' blood routine tests,liver and kidney function,coagulation,cardiac function,and other clinical indicators before and after blood transfusion were analyzed and compared in conjunction with the patients'clinical manifestations.Results:The patient's blood group was A/CcDEe.Before two transfusion,the anti-body screening were positive which identification were anti-Fya and anti-Fya combined with anti-Jkb respectively,while the Coomb's test were positive with anti-C3 and anti-IgG combined with anti-C3 respectively.No agglutination and hemolysis was observed in saline medium cross-matching test before two transfusion of Fya-red blood cell.But before re-transfusion agglutinated reaction was observed in cross-matching test by DG Gel Coombs,which strength was 2+on whether major or minor side.The patient developed soy sauce urine/hemoglobinuria and fever after transfused Fya-red blood cell again.Primary laboratory indicators were observed to be elevated,include C-reactive protein from 3.06 mg/L to 29.97 mg/L,total bilirubin from 21.4 μmol/L to 276.3 μmol/L,direct bilirubin from 8.4 μmol/L to 135.6 μmol/L,lactate dehydrogenase from 166 U/L to 1453 U/L.Urinary free hemoglobin test was 4+.The main laboratory indicators reflecting the heart,liver,kidney and circulatory coagulation function also have vary increased and gradually returned to normal after a week. Conclusion:Jkb-incompatible transfusion of the Kidd blood group system can lead to acute hemolytic transfusion reaction,but in emergency implementing incompatible transfusion due to IgG antibodies outside of the primary blood group (such as ABO/RhD)can ensure the implementation of emergency operation.

According to the theory of traditional Chinese medicine(TCM),benign prostatic hyperplasia(BPH)belongs to the category of"Jing Long".Clinical management of BPH in TCM is root-aimed and kidney-targeted,in combination with the treatment of other viscera based on the syndrome differentiation of zang-fu organs.The neuro-endocrine-immune network of modern medicine is simi-lar to the holistic concept of TCM.Based on the study of the neuro-endocrine-immune network,with kidney deficiency as the root of pathogenesis,and starting from the classification of viscera,this review elucidates the etiologic mechanisms of BHP from the perspec-tive of Chinese and Western medicine and provides some reference for medication.

OBJECTIVE: To evaluate the association between serum uric acid (SUA) and kidney function decline. METHODS: Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis. The kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) decrease by > 3 mL/min per 1.73 m ². Multivariable logistic regression was applied to determine the association between SUA and kidney function decline. The shape of the association was investigated by restricted cubic splines. RESULTS: A total of 7,346 participants were included, of which 1,004 individuals (13.67%) developed kidney function decline during the follow-up of 4 years. A significant dose-response relation was recorded between SUA and the kidney function decline ( OR 1.14, 95% CI 1.03-1.27), as the risk of kidney function decline increased by 14% per 1 mg/dL increase in SUA. In the subgroup analyses, such a relation was only recorded among women ( OR 1.22, 95% CI 1.03-1.45), those aged < 60 years ( OR 1.22, 95% CI 1.05-1.42), and those without hypertension and without diabetes ( OR 1.22, 95% CI 1.06-1.41). Although the dose-response relation was not observed in men, the high level of SUA was related to kidney function decline ( OR 1.83, 95% CI 1.05-3.17). The restricted cubic spline analysis indicated that SUA > 5 mg/dL was associated with a significantly higher risk of kidney function decline. CONCLUSION The SUA level was associated with kidney function decline. An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; East Asian People ; Glomerular Filtration Rate ; Kidney/physiopathology* ; Longitudinal Studies ; Risk Factors ; Uric Acid/blood*

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.