OBJECTIVES: To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism. METHODS: Mouse bone marrow-derived macrophages (BMDM), human monocytic leukemia cell line THP-1, and peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were pre-treated with avitinib, followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin, monosodium urate (MSU) crystals, or adenosine triphosphate (ATP). Non-canonical NLRP3 inflammasome activation was induced via intracellular transfection of lipopolysaccharide (LPS). Western blotting was used to detect the secretory protein markers of NLRP3 inflammasome activation and assess pyroptosis, and the levels of inflammatory cytokines in cell culture supernatant were determined with ELISA. In a mouse model of LPS-induced septic shock, the effect of avitinib treatment on the levels of inflammatory cytokines in serum and peritoneal lavage fluid were examined with ELISA, and survival curves of the mice were plotted using the Kaplan-Meier method. RESULTS: Avitinib significantly inhibited NLRP3 inflammasome activation in multiple cell types, and dose-dependently reduced IL-1β secretion and caspase-1 cleavage while suppressing GSDMD-mediated pyroptosis without obviously affecting IL-6 or TNF-α levels. In the mouse models of LPS-induced septic shock, avitinib significantly lowered IL-1β levels in serum and peritoneal fluid and extended survival time of the mice. CONCLUSIONS Avitinib suppresses NLRP3 inflammasome activation and alleviates septic shock in mice.
Animals ; Shock, Septic/metabolism* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes/drug effects* ; Humans ; Macrophages/metabolism* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides

In November 23, 2023, a patient with 9 digits traumatic crush injury by machine compression was emergently admitted to the Department of Hand and Microsurgery, Sichuan Modern Hospital. Emergency procedures included amputation the distal stumps and replantation of proximal phalanges of left ring and little fingers. Wounds in both hands were temporarily covered with bone cement. On December 4, 2023, reconstruction of 5 digits were performed. Digital defects were: Type Ⅲ defects of left index and middle fingers and right thumb and index fingers and Type IV defect of right middle finger. All 5 reconstructed digits survived. Subsequent refinements yielded favourable outcomes and all donor toes were preserved completely. At the 14-month follow-up, the reconstructed digits exhibited satisfactory appearance and length without difficulties in daily life and at work.

Objective:To evaluate the clinical efficacy of a replay propeller distal perforator flap of the lateral circumflex femoral artery in reconstruction of the donor site defect left by the harvest of a free anterolateral thigh perforator flap (ALTPF).Methods:From June 2023 to June 2024, retrospective analysis of 11 patients with foot and ankle soft tissue defects were treated in the Department of Microsurgery, Sichuan Modern Hospital. The patients were 7 males and 4 females, aged 9-57 (average 28.6) years. Causes of injury were car accident (5 patients), machine crush (5 patients) and skin necrosis following a fall (1 patient). The size of soft tissue defects was 8.0 cm ×11.0 cm - 9.0 cm×14.5 cm. A reversed perforator island flap of distal descending branch of the lateral circumflex femoral artery was prepared to reconstruct the defect left at the donor site after the harvest of a free ALTPF. The ALTPFs were 8.5 cm × 11.5 cm to 9.5 cm × 15.5 cm in size, and the sizes of the perforator flap of descending branch of lateral circumflex femoral artery designed to reconstruct the donor site defects were at 5.0 cm × 9.0 cm to 6.0 cm × 12.0 cm. After the surgery, scheduled follow-ups were carried out at outpatient clinic and via telephone and WeChat reviews. Wound healing at recipient and donor sites, flap survival and functional recovery were observed.Results:All flaps survived smoothly after surgery, and the wounds in the donor and recipient sites healed primarily. No vascular compromise, wound dehiscence or significant swelling occurred. A total of 9 patients completed the 6-18 months postoperative follow-up, with an average of 11 months. Two patients lost in the follow-up. Only linear scars left in the donor sites, without significant impact on the thigh function. The colour and appearance of the flaps were natural.Conclusion:It is effective to use a distal replay flap of the descending branch of lateral circumflex femoral artery for reconstruction of the donor site defect left by the harvest of a free ALTPF.

Objective: To compare quality control (relative purity and specific activity) and process control [plasminogen (Pg) antigen recovery and potency recovery] indexes of samples before and after adding the Q chromatography step to the full chromatography process of human Pg, thereby determining whether the addition of this step could improve Pg recovery by affinity chromatography. Methods: A Q chromatography step was added before the Pg affinity chromatography in the original Pg chromatography process. The loading solution, flow through solution and eluate of Q chromatography and Pg affinity chromatography were collected. The potency of coagulation factor Ⅱ (FⅡ), Ⅶ (FⅦ), Ⅷ (FⅧ), Ⅸ (FⅨ), and Ⅹ(FⅩ) were detected by the coagulation method, the total protein content was detected by the BCA method, and the Pg potency was detected by the chromogenic substrate method. The content of specific plasma proteins was detected by immunoturbidimetry, the potency recovery of coagulation factors was calculated, and the flow direction of coagulation factors was analyzed. The recovery of different plasma protein antigens were calculated, and the distribution of impurity proteins was analyzed. The relative purity and specific activity of Pg, antigen content, and potency recovery in the target fractions were calculated and compared with the original process indicators, so as to determine the effect of adding Q chromatography on the original process. Furthermore, the reproducibility after process modification was assessed. Results: 100% of FⅡ, FⅩ, and FⅨ, 87.81% of FⅧ, and 40.44% of FⅦ in filtered plasma were removed by Q chromatography. The residual FⅦ (53.26%) and FⅧ (13.30%) in Q flow-through fraction were completely removed by Pg affinity chromatography. In both the original process (without Q-chromatography) and the modified process (with Q-chromatography), non-target plasma proteins mainly existed in the flow-through fraction of Pg affinity chromatography. The antigen recovery of IgM, ceruloplasmin (CER), and fibronectin (FNC) in Q-chromatography flow-through fraction were reduced. In contrast, antigen recovery of other plasma proteins [IgG, IgA, Pg, albumin (AlB), alpha-1-antitrypsin (AAT), and fibrinogen (Fg)] were all >90%, which were consistent with the protein composition and proportion in the original affinity chromatography loading solution. Compared with the recovery rate of Pg antigen in the original process (74.4%), the total recovery of Pg antigen in the modified process was significantly increased (89.97%). Compared with the recovery of IgG (97.48%) and Fg (95.32%) in the Pg affinity flows-through fraction of the original process, the modified process resulted in a slight reduction in the recovery of IgG (94.60%), while the recovery of Fg was not affected (95.05%). The potency recovery rate, specific activity, and relative purity of Pg after Q chromatography were 99.3%, 0.016 U/mg, and 0.15%. These values were the same as those of Pg affinity chromatography loading solution by the original process, indicating that introduction of Q chromatography did not affect subsequent Pg affinity chromatography. Compared with the recovery of Pg antigen in three batches of the original process (66.49±1.02)%, the recovery of Pg antigen in the affinity chromatography eluent of the modified process [five batches; (77.43±4.43)%] was significantly improved. Furthermore, the potency recovery was (86.80±4.28)%, the relative purity was (81.99±1.25)%, the specific activity was (8.679±1.073)U/mg, and the process was reproducible. Conclusion: The addition of Q chromatography could improve the recovery of Pg affinity chromatography in the full chromatography process.

Objective To investigate the relationship between the expression of platelet autophagy related factors and peritoneal metastasis of gastric cancer.Methods The data of 360 patients with gastric cancer who underwent surgery in Hunan Provincial People's Hospital from January 2021 to May 2023 were reviewed.Patients were divided into non-peritoneal metastasis group(n=322)and peritoneal metastasis group(n=38)according to whether peritoneal metastasis occurred or not.The following information was collected:patient's personal information(i.e.age,sex,body mass index)and tumor characteristics(i.e.location,size,pathological type,histopathological differentiation,lymphatic infiltration).Platelets were collected from all subjects,and the levels of autophagy-associated protein 7(ATG7),benzalkonium chloride 1(BECN1),microtubule-associated protein 1 light chain 3(LC3)and sequestosome 1(p62)were measured by enzyme-linked immunosorbent assay(ELISA).Results Among the 360 patients included,peritoneal metastasis was detected in 38 cases.Compared with the non-peritoneal metastasis group,the peritoneal metastasis group exhibited decreased BMI(P<0.05),while the tumor size,non-ulcerative tumor,number of lymph node metastasis,infiltration depth,number of cases of lymphatic invasion,platelet count,platelet LC3-Ⅱ level,platelet ATG7 level and CEA level were increased(P<0.05).Multivariate logistic regression analysis showed that BMI(OR=1.094),lymphatic invasion(OR=2.658),and LC3-Ⅱ(OR=3.793)and ATG7(OR=2.010)were independent influencing factors for peritoneal metastasis in patients with gastric cancer(P<0.05).LC3-Ⅱ>2.59ng/ml had the highest ability to predict peritoneal metastasis in patients with gastric cancer(AUC=0.932),followed by ATG7(AUC=0.916).Conclusions Elevated levels of platelet LC3-Ⅱ and ATG7 are independently related to peritoneal metastasis in patients with gastric cancer,and can be used to predict the occurrence of peritoneal metastasis,which is helpful to guide individualized treatment.

In November 23, 2023, a patient with 9 digits traumatic crush injury by machine compression was emergently admitted to the Department of Hand and Microsurgery, Sichuan Modern Hospital. Emergency procedures included amputation the distal stumps and replantation of proximal phalanges of left ring and little fingers. Wounds in both hands were temporarily covered with bone cement. On December 4, 2023, reconstruction of 5 digits were performed. Digital defects were: Type Ⅲ defects of left index and middle fingers and right thumb and index fingers and Type IV defect of right middle finger. All 5 reconstructed digits survived. Subsequent refinements yielded favourable outcomes and all donor toes were preserved completely. At the 14-month follow-up, the reconstructed digits exhibited satisfactory appearance and length without difficulties in daily life and at work.

Objective:To evaluate the clinical efficacy of a replay propeller distal perforator flap of the lateral circumflex femoral artery in reconstruction of the donor site defect left by the harvest of a free anterolateral thigh perforator flap (ALTPF).Methods:From June 2023 to June 2024, retrospective analysis of 11 patients with foot and ankle soft tissue defects were treated in the Department of Microsurgery, Sichuan Modern Hospital. The patients were 7 males and 4 females, aged 9-57 (average 28.6) years. Causes of injury were car accident (5 patients), machine crush (5 patients) and skin necrosis following a fall (1 patient). The size of soft tissue defects was 8.0 cm ×11.0 cm - 9.0 cm×14.5 cm. A reversed perforator island flap of distal descending branch of the lateral circumflex femoral artery was prepared to reconstruct the defect left at the donor site after the harvest of a free ALTPF. The ALTPFs were 8.5 cm × 11.5 cm to 9.5 cm × 15.5 cm in size, and the sizes of the perforator flap of descending branch of lateral circumflex femoral artery designed to reconstruct the donor site defects were at 5.0 cm × 9.0 cm to 6.0 cm × 12.0 cm. After the surgery, scheduled follow-ups were carried out at outpatient clinic and via telephone and WeChat reviews. Wound healing at recipient and donor sites, flap survival and functional recovery were observed.Results:All flaps survived smoothly after surgery, and the wounds in the donor and recipient sites healed primarily. No vascular compromise, wound dehiscence or significant swelling occurred. A total of 9 patients completed the 6-18 months postoperative follow-up, with an average of 11 months. Two patients lost in the follow-up. Only linear scars left in the donor sites, without significant impact on the thigh function. The colour and appearance of the flaps were natural.Conclusion:It is effective to use a distal replay flap of the descending branch of lateral circumflex femoral artery for reconstruction of the donor site defect left by the harvest of a free ALTPF.

Objective To analyze the current status of dyslipidemia among employees in a petrochemical enterprise and its influencing factors. Methods A total of 1 636 employees from a petrochemical enterprise were selected as the research subjects by the judgment sampling method. Peripheral venous blood was collected from the research subjects to detect total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low- density lipoprotein cholesterol (LDL-C) in serum. The Effort-Reward Imbalance (ERI) Questionnaire was used to investigate occupational stress in the ERI model. Results The detection rate of dyslipidemia among the research subjects was 52.7%. The detection rates of abnormal total cholesterol, triglyceride, LDL-C, and HDL-C were 35.7%, 31.4%, 24.3%, and 10.0%, respectively. The detection rate of high occupational stress among the research subjects was 26.3%. The result of multivariate logistic regression analysis showed that the risks of dyslipidemia in overweight and obese employees were higher than that of normal body mass [ odds ratio (OR) and 95% confidence interval (CI) were 2.111 (1.692-2.634) and 2.346 (1.591-3.458), both P<0.01]. The risk of dyslipidemia in lean body mass employees was lower than those with normal body mass [OR (95%CI) was 0.130 (0.030-0.564), P<0.05]. The risk of dyslipidemia in smokers was higher than that in non-smokers [OR (95%CI) was 1.462 (1.124-1.902), P<0.01]. Employees with 20-30 years and ≥ 30 years of service had higher risks of dyslipidemia than those with <10 years of service [OR (95%CI) were 1.411 (1.038-1.919) and 1.869 (1.202-2.906), respectively, both P<0.05]. The risk of dyslipidemia among employees with high effort level of occupational stress in ERI model was higher than those with low effort level [OR (95%CI) was 1.351(1.045-1.745), P<0.05]. Conclusion Dyslipidemia prevalence is relatively high among the petrochemical enterprise employees. Overweight, obesity, smoking, long service years, and occupational stress in ERI model are influencing factors of dyslipidemia. To prevent dyslipidemia, it is necessary to strengthen blood lipid monitoring and lifestyle intervention in personnel with overweight, obesity, smoking, long service years, and occupational stress in ERI model.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.