The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To analyse the acupoint selection rules of acupuncture in the treatment of non-small cell lung cancer,and to provide reference for clinical application.Methods The clinical research,practitioner's experience and academic thought of acupuncture treatment for non-small cell lung cancer were retrieved to obtain the acupuncture prescriptions of modern practitioners for the treatment of non-small cell lung cancer.Based on the statistical methods of acupoint frequency,prescription rules,acupoint clustering and core combination,the core theoretical system and acupoint selection rules of acupuncture treatment of non-small cell lung cancer by modern practitioner were analyzed.Results According to the inclusion and exclusion criteria,94 acupuncture prescriptions were finally included.There were eight acupoints used more than 20 times,which were Zusanli(ST36),Neiguan(PC6),Feishu(BL13),Sanyinjiao(SP6),Qihai(RN6),Guanyuan(RN4),Hegu(LI4)and Zhongwan(RN12).The top three high-frequency acupoint combinations were Zusanli-Neiguan,Zusanli-Sanyinjiao and Qihai-Zusanli;correlation analysis showed that the correlation strength of Zusanli-Neiguan was the highest,followed by Zusanli-Sanyinjiao and Zusanli-Hegu.The cluster analysis showed that the acupoints with frequency＞10 times could be divided into three categories.Category 1 includes:Zusanli,Neiguan,Sanyinjiao,Hegu;category 2 includes Guanyuan,Qihai,Zhongwan,Xuehai(SP10),Taichong(LR3);category 3 consists of two parts,one is Danzhong(RN17),Tiantu(RN22),Fenglong(ST40),Taiyuan(LU9);the second is Feishu(BL13),Lieque(LU7),Chize(LU5),Zhongfu(LU1),Xinshu(BL15),Gaohuang(BL43),Fengmen(BL12).Conclusion The core acupoints for acupuncture treatment of non-small cell lung cancer include four categories:① invigorating the spleen and benefiting qi:Zusanli,Sanyinjiao,Zhongwan and Fenglong;②replenishing and supplementing original qi:Guanyuan,Qihai and Gaohuang;③regulating qi and broadening the chest:Danzhong,Neiguan,Tiantu and Fengmen;④ diffusing the lung and ventilating qi:Feishu,Hegu,Chize and Lieque.The three treatment methods of replenishing qi,regulating qi and venting pathogen are the basis of acupuncture treatment of advanced non-small cell lung cancer.The core idea of acupuncture treatment of non-small cell lung cancer focuses on supplementation,supplemented by dredging,and to dredge and supplement simultaneously.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To investigate the effect of propofol or different doses of remimazolam on effective dose(ED50)of sufentanil in elderly patients with tracheal intubation response by sequential method.Methods Elderly patients,American Society of Anesthesiologists(ASA)Ⅰ and Ⅱ,aged 65-80 years,undergoing elective surgery under general anesthesia with endotracheal intubation from October to December 2022 were selected and randomly divided into 4 groups:Group P(propofol 2mg/kg)and group R1,R2 and R3(remimazolam 0.2,0.3 and 0.4mg/kg)were administered intravenously.During anesthesia induction,sufentanil was given with the dose set by Dixon sequential method,followed by intravenous injection of propofol or corresponding dose of remimazolam and cisatracurium 0.15mg/kg.Tracheal intubation was performed when train of four(TOF)count was 0.If the tracheal intubation response is positive,the sufentanil dose of the next patient is increased by 1 concentration gradient,otherwise,the sufentanil dose is decreased by 1 concentration gradient,and the ratio between adjacent concentrations is 1∶1.1,until 7 turning points appear and the study is terminated.Probit regression analysis was used to calculate the median ED50 and 95%effective dose(ED95)of sufentanil for suppressing tracheal intubation response in elderly patients,and the corresponding 95%CI.The incidence of hypotension,bradycardia,injection pain and other adverse reactions were recorded.Results A total of 113 elderly patients were included in this study,including 24,28,30 and 31 patients in P,R1,R2 and R3 groups,respectively.The ED50 and ED95 and corresponding 95%CI of sufentanil for suppressing tracheal intubation response in elderly patients with propofol 2 mg/kg or remimazolam 0.2,0.3,0.4mg/kg were:The ED50 and ED95 of group P were 0.236μg/kg(95%CI:0.218-0.256)and 0.266μg/kg(95%CI:0.250-0.398),respectively.The ED50 and ED95 of group R1 were 0.284μg/kg(95%CI:0.265-0.309)and 0.329μg/kg(95%CI:0.306-0.478),respectively.The ED50 and ED95 of R2 group were 0.239μg/kg(95%CI:0.221-0.260)and 0.282μg/kg(95%CI:0.261-0.415),respectively.The ED50 and ED95 of R3 group were 0.198μg/kg(95%CI:0.182-0.211)and 0.231μg/kg(95%CI:0.216-0.303),respectively.The incidence of hypotension,bradycardia and injection pain in R1,R2 and R3 groups were lower than those in P group(P<0.05).The ED50 of sufentanil in group R2 was similar to that in group P,but the incidence of hypotension and injection pain in group R2 was lower than that in group P.Conclusion With the increase of the dose of remimazolam,the ED50 of sufentanil to inhibit tracheal intubation reaction in elderly patients gradually decreased,and in the case of similar ED50,the incidence of hypotension,bradycardia and injection pain induced by remimazolam was lower than that induced by propofol,so remimazolam induction was more advantageous in general anesthesia for tracheal intubation in elderly patients.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To develop a portable collection device of human exhaled breath condensate(EBC)based on natural breathing to meet the needs for rapid screening of human respiratory tract(especially lower respiratory tract)infections.Methods The device consisted of a refrigeration unit,a heat dissipation unit and a condensation unit.The refrigeration unit adopted a TES1-7102 thermoelectric Peltier cooler semiconductor as the refrigeration element;the heat dissipation unit was composed of a high thermal conductivity aluminum heat sink and a high-speed brushless cooling fan;the condensation unit was made up of a cold guide plate and a condenser,in which the cold guide plate was made of thin sheet of aluminum alloy,and the condenser was prepared by 3D printing technology and made of hydrophobic polylactic acid,with primary and secondary 2-stage guide grooves and an ultra-thin condensing surface.The performance of the device was verified in terms of cooling,thermal conductivity,condensation and human EBC collection and content analysis.Results Performance analysis showed that after refrigeration began the temperature difference between the condenser surface and the exhaled gas met the requirements of the condenser,and no obvious thermal resistance was found on the condensing surface so that large droplets could be formed rapidly and then be collected after the gas-liquid phase change of the exhaled gas on the condensing surface.Human EBC collection and content analysis indicated the device realized home self-collection of EBCs from people of all ages,and the concentrations of interleukins,C-reactive protein and other inflammation-related indexes and the pH value of the collected EBC samples were all correlated with respiratory infections in the subjects.Conclusion The device developed with easy operation avoids the discomfort of blowing collection and the risk of saliva contamination,and is worthy promoting for rapid diagnosis and dynamic monitoring of respiratory tract infection and other related diseases.[Chinese Medical Equipment Journal,2024,45(8):32-37]

Objective To explore the median effective dose of propofol or cyclopofol combined with alfentanil in inhibiting body movement response during induced abortion.Methods From October 2021 to April 2022,patients aged 18-35 years,body mass index(BMI)18-28 kg/m2,American Society of Anesthesologists(ASA)I or II,fetal age<10 weeks,first pregnancy or no history of vaginal delivery were selected for elective painless induced abortion in Gynecological Surgery Center of the Second Hospital of Jiaxing.Patients were divided into 2 groups using a random number table method:propofol group(group P)and cyclopofol group(group C).During anesthesia induction,intravenous injection of alfentanil was followed by administration of propofol or cyclopofol with a dose set by the modified sequential method.If the patient had involuntary limb movement during surgery and affected the operation of the operator and needed additional anesthetic drugs,it was judged as a positive reaction,and intravenous propofol or cyclopofol 0.5mg/kg or 0.1mg/kg was added,and the next patient's propofol or cyclopofol was increased by a dose gradient.Conversely,the next patient was given a dose gradient of 0.5mg/kg propofol or 0.1mg/kg cyclopofol,respectively.Probit regression analysis was used to calculate the median effective dose(ED50),95%effective dose(ED95)and corresponding confidence interval(CI)of propofol and cyclopofol.Results The ED50(95%CI)and ED95(95%CI)of propofol in group P were 1.815(1.315-2.319)mg/kg and 2.901(2.368-6.447)mg/kg,respectively.The ED50(95%CI)and ED95(95%CI)of cyclopofol in group C were 0.381(0.279-0.484)mg/kg and 0.613(0.501-1.344)mg/kg,respectively,and the equivalent ratio of the two was 4.76(4.71-4.79).Conclusion The potency of ciprofol in inhibiting movement response during induced abortion is greater than that of propofol.

Objective To explore the clinical effect of different doses of alfentanil combined with low-dose propofol in painless colonoscopy in elderly patients.Methods A total of 120 elderly patients undergoing elective painless colonoscopy from January to March 2022,aged 65 to 80 years,gender unlimited,body mass index(BMI)18-28kg/m2,American Society of Anesthesiologists(ASA)grade Ⅰ～Ⅱ.Patients were included in the three groups by random number tables:alfentanyl 5μg/kg(N1),alfentanyl 7.5μg/kg(N2),and alfentanyl 10μg/kg(N3),40 patients in each group.Record the heart rate,mean arterial pressure,and oxygen saturation were recorded before anesthesia(T1),after anesthesia induction(T2),colonoscopy(T3),colonoscopy reaching the ileocecum(T4),and at the end of examination(T5).The success rate of anesthesia sedation,dosage of propofol,sedative induction time,colonoscopy time,sedative recovery time,use of vasoactive drugs and physician satisfaction of the three groups were recorded.The incidence of intraoperative hypoxemia,hypotension,spontaneous ycardia,bradycardia,postoperative nausea and dizziness,and postoperative fatiguesyndrome(POFS)and the occurrence of adverse reactions.Results Compared with T1,the mean arterial pressure in T2-T5 patients decreased significantly(P＜0.05),and the heart rate at T3 increased significantly(P＜0.05)in N1,the total dosage,induction time,induction time,awakening time and vasoactive drug use were decreased in N2 and N3,and the success rate of anesthesia sedation was significantly increased(P＜0.05).Comparing the N2 group,physician satisfaction decreased in the N1 and N3 groups(P＜0.05).The incidence of intraoperative hypotension and postoperative POFS decreased in the N2 and N3 groups(P＜0.05)and in the N1 and N2 groups(P＜0.05).Conclusion Afunentanil 7.5pg/kg compound propofol can be used safely and effectively for painless colonoscopy in elderly patients,and the incidence of adverse reactions is low,which improves the quality of postoperative recovery of patients,and is worthy of clinical promotion and application.