Objective To investigate the influence of body mass index(BMI)on individualized analgesic effect,inflammatory factors and safety of sufentanil in elderly patients after proximal femoral nail anti-rotation(PFNA)surgery.Methods A total of 161 elderly patients who received PFNA surgery in Nanjing Drum Tower Hospital Group Suqian Hospital from January 2022 to December 2023 were selected as study subjects.Patients with BMI<18.5 kg/m2 were set as Group A,patients with BMI ranging from 18.5 kg/m2 to 23.9 kg/m2 were set as Group B,patients with BMI ranging from 24.0 kg/m2 to 35.0 kg/m2 were set as Group C.After operation,individualized analgesia was performed with an intravenous patient-controlled analgesia pump of 2 μg/kg sufentanil based on body weight,and the postoperative pain degree,inflammatory factors,analgesia condition and adverse reactions of patients in the three groups were compared.Results At 8 hours,12 hours,24 hours and 48 hours after surgery,the pain visual analogue scale(VAS)scores of patietns in group B and group C were significantly lower than those in group A(P<0.05).At 12 hours,24 hours and 48 hours after surgery,the pain VAS scores of patients in group C were significantly lower than those in group B(P<0.05).The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)1 day after surgery of patients in group B and group C were significantly lower than those in group A(P<0.05).The pressing times of analgesia pump and the duration of obvious pain within 48 hours after surgery of patients in group A were significantly more/longer than those in group B and group C(P<0.05),and the analgesic satisfaction score was significantly lower than those in group B and group C(P<0.05).The total incidence of analgesic adverse reactions in group C was significantly higher than those in group A and group B(P<0.05).Conclusion BMI may affect the individualized analgesic effect,inflammatory factors and safety of sufentanil in elderly patients undergoing PFNA surgery.Underweight patients may have insufficient analgesia,while overweight or obese patients may have excessive analgesia,which may affect the analgesic safety.

Objective To investigate the influence of body mass index(BMI)on individualized analgesic effect,inflammatory factors and safety of sufentanil in elderly patients after proximal femoral nail anti-rotation(PFNA)surgery.Methods A total of 161 elderly patients who received PFNA surgery in Nanjing Drum Tower Hospital Group Suqian Hospital from January 2022 to December 2023 were selected as study subjects.Patients with BMI<18.5 kg/m2 were set as Group A,patients with BMI ranging from 18.5 kg/m2 to 23.9 kg/m2 were set as Group B,patients with BMI ranging from 24.0 kg/m2 to 35.0 kg/m2 were set as Group C.After operation,individualized analgesia was performed with an intravenous patient-controlled analgesia pump of 2 μg/kg sufentanil based on body weight,and the postoperative pain degree,inflammatory factors,analgesia condition and adverse reactions of patients in the three groups were compared.Results At 8 hours,12 hours,24 hours and 48 hours after surgery,the pain visual analogue scale(VAS)scores of patietns in group B and group C were significantly lower than those in group A(P<0.05).At 12 hours,24 hours and 48 hours after surgery,the pain VAS scores of patients in group C were significantly lower than those in group B(P<0.05).The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)1 day after surgery of patients in group B and group C were significantly lower than those in group A(P<0.05).The pressing times of analgesia pump and the duration of obvious pain within 48 hours after surgery of patients in group A were significantly more/longer than those in group B and group C(P<0.05),and the analgesic satisfaction score was significantly lower than those in group B and group C(P<0.05).The total incidence of analgesic adverse reactions in group C was significantly higher than those in group A and group B(P<0.05).Conclusion BMI may affect the individualized analgesic effect,inflammatory factors and safety of sufentanil in elderly patients undergoing PFNA surgery.Underweight patients may have insufficient analgesia,while overweight or obese patients may have excessive analgesia,which may affect the analgesic safety.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.

This study aims to investigate the efficacy, safety, and cost-effecctiveness of Qizhi Weitong Granules in the treatment of functional dyspepsia. Specifically, two commonly used clinical protocols for the treatment of functional dyspepsia were selected: Qizhi Weitong Granules+Mosapride vs Mosapride alone(control). Meta-analysis of previous clinical studies was performed to examine the efficacy and safety, and pharmacoeconomic evaluation was carried out according to the results of the Meta-analysis. The cost-effectiveness analysis was carried out to elucidated the incremental cost-effectiveness ratio(ICER), and the sensitivity was analyzed with tornado dia-gram and Monte Carlo simulation. The willingness-to-pay threshold of patients for functional dyspepsia was investigated and compared with the ICER to evaluate whether Qizhi Weitong Granules was cost-effective. The result showed that the effective rate of Qizhi Weitong Granules combined with Mosapride in the treatment of functional dyspepsia was 95.49%, which was higher than that of Mosapride alone(73.30%)(OR=8.52, 95%CI[4.36, 16.64])(P<0.000 1). The two groups showed no significant difference in safety. The price of Qizhi Weitong Granules+Mosapride was higher than that of Mosapride alone. The ICER was 640.29 CNY, 1 506.67 CNY lower than the willingness-to-pay threshold. The sensitivity analysis showed that the analysis results were relatively stable. Thus, Qizhi Weitong Granules+Mosapride is safe, effective, and economical in the treatment of functional dyspepsia, which should be further promoted in clinical settings.
Benzamides ; Cost-Benefit Analysis ; Dyspepsia/drug therapy* ; Economics, Pharmaceutical ; Gastrointestinal Agents/therapeutic use* ; Humans ; Morpholines ; Treatment Outcome

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

Three phenylpropanoid glycosides were purified by extensive chromatographic techniques including column chromatography over microporous resin, MCI, diol, sephadex LH-20, reverse phase C_(18) from water-extracts of Sophorae Tonkinensis Radix et Rhizoma. Their planar structures were elucidated by combination of various spectroscopic method, such as IR, UV, MS, and NMR. The absolute configuration of aglycone was determined by quantum chemical calculations. Their structures were elucidated as(8R)-3-(4-hydroxyphenyl)-1-propanol-2-O-β-D-glucopyranoside(1), kalopanaxin D(2),(E)-4-hydroxycinnamyl alcohol 4-O-[2'-O-β-D-apiofuranosyl(1″→2')]-β-D-glucopyranoside(3). Compound 1 was undescribed previously. Compounds 2 and 3 were firstly isolated from Sophora genus.
Drugs, Chinese Herbal ; Ethanol ; Glycosides ; Rhizome ; Sophora

Objective: To construct a new CD123- specific chimeric antigen receptor in order to provide a foundation for immunotherapy of CD123 positive leukemia. Methods: A hybridoma strain (6E11) capable of stably secreting CD123 antibody was obtained by a monoclonal screening technique, and the hybridoma cells were expanded and injected intraperitoneally to the pretreated Balb/c mice. Ascites was collected and purified to obtain the monoclonal antibody (mAb) . The affinity and specificity of 6E11 mAb were measured. The variable regions of the heavy and light chains of the 6E11 mAb were cloned by RT-PCR from the 6E11 mouse hybridoma. We generated a new CD123 specific chimeric antigen receptor with a scFv fragment derived from 6E11 antibody, designated as 6E11 CAR. T cells were transduced with lentiviral supernatant from 293T cells transfected with 6E11 CAR plasmid to generate 6E11 CAR-T cells. The specific cytotoxicity of 6E11 CAR-T against CD123(+) acute myeloid leukemia (AML) cell lines and primary AML cells in vitro were evaluated by co-culture experiments, degranulation experiments and cytokine releasing assay. Results: ① A hybridoma cell line 6E11 stably secreting anti-human CD123 antibody was developed and its variable region sequences were obtained. ② The 6E11 mAb has high affinity for CD123 protein (Kd value: 2.1 nmol/L) . The 6E11 mAb specifically recognizes CD123(+) cell line THP-1 cells and does not respond to CD123(-) cell line Jurkat cells. ③ 6E11 CAR-T cells were successfully generated with a CAR expression rate higher than 60%. ④ 6E11 CAR-T cells could specifically kill CD123(+) MV4-11 cell line but had no killing effect on the CD123(-) K562 cell line. Compared with vector-T cells, 6E11 CAR-T cells have higher killing rate to MV4-11 cells[ (98.60±1.20) %vs (20.28±6.74) %, P<0.001]. ⑤ MV4-11 cells activated 6E11 CAR-T cells significantly but not Vector-T cells[ (26.33±3.30) %vs (1.17±0.06) %, P<0.001]. ⑥ 6E11 CAR-T cells released more cytokines than vector-T cells when co-cultured with MV4-11[IL-2: (92.90±1.51) pg/ml vs (6.05±3.41) pg/ml, P<0.001; TNF-α: (1 407.20±91.95) pg/ml vs (7.86±0.85) pg/ml, P<0.001; IFN-γ: (5 614.60±170.17) pg/ml vs (8.42±2.70) pg/ml, P<0.001]. The IFN-γ, IL-2 and TNF-α in the 6E11 CAR-T group were similar to those in the Vector-T group when co-cultured with K562. ⑦ 6E11 CAR-T cells could be activated by bone marrow mononuclear cells (BMMNC) derived from CD123(+) AML patients and effectively kill these BMMNC cells from CD123(+) AML patients. Conclusion: 6E11 hybridoma cell line can stably secrete highly specific monoclonal antibodies against human CD123, which can be used to detect the expression of human CD123. It can also be used to target human CD123 protein in tumor immunotherapy. CD123 CAR-T cells with 6E11 Ig variable region sequence have specific anti-leukemic activity in vitro, which may provide a new option for further clinical research of AML.
Animals ; Cell Line, Tumor ; Humans ; Interleukin-3 Receptor alpha Subunit ; Leukemia, Myeloid, Acute ; Mice ; Receptors, Chimeric Antigen ; Single-Chain Antibodies