Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective The pathogenesis of EAP in rats based on the TLR4/NF-κB-NLRP3 inflammasome signaling pathway was explored.Methods Randomly divide 12 male SD rats into 4 groups using the number table,namely normal group(N),model group(M),Caspase-1 inhibitor group(Caspase-1),and NLRP3 inhibitor MCC950 group(NLRP3),with 3 rats in each group.After drug intervention,relevant indicators were observed by using HE staining,ELISA,WB methods.Results Compared with the N group,the M group rats had showed significant damage in prostate gland structure and infiltration of inflammatory cells.Compared with group N,the expression of TLR4,P-NF-κB P65,NLRP3,ASC,Cleaced-Caspase-1,Cleaced-IL-1β,and IL-18 proteins in the prostate tissue of group M rats had increased(P<0.01).Compared with group M,the expression of TLR4,P-NF-κB P65,NLRP3,ASC,Cleaced-Caspase-1,Cleaced-IL-1β,and IL-18 proteins in the NLRP3 and Caspase-1 groups had significantly reduced(P<0.01).The serum levels of IL-1 β,IL-6,IL-8,IL-17A,IL-18,IFN-γ,and TNF-α in group M rats had been significantly higher than those in group N(P<0.01).But the serum levels of IL-10 had been slightly lower and no statistical significance.The serum levels of IL-1β,IL-6,IL-8,IL-17A,IL-18,IFN-γ,and TNF-α in group M rats had been lower than those in group N(P<0.01 or P<0.05),the serum IL-10 level had increased(P<0.01).Conclusion The activation of TLR4/NF-κB-NLRP3 inflammasome signaling path-way promotes the occurrence and development of prostatitis in EAP rats.

A male patient,51 years old,was diagnosed as follows:① type 2 diabetes mellitus;② grade 2 hypertension(extremely high risk).To improve circulation,the patient was administered pentoxifylline injection 0.2 g mixed with 250 mL of 0.9％sodium chloride injection via an intravenous drip,once daily(qd).After 4 days of treatment,liver function tests showed the following results:alanine aminotransferase(ALT)at 2 390.80 U·L-1,aspartate aminotransferase(AST)at 948.28 U·L-1,and gamma-glutamyltransferase(GGT)at 517.81 U·L-1.It was highly probable that pentoxifylline caused abnormally elevated liver enzymes,with a clear drug-related association.After discontinuing pentoxifylline injection and initiating liver-protecting and en-zyme-lowering treatment,the liver function indicators gradually improved.Enhanced monitoring during the clinical use of pentoxi-fylline is essential to ensure patient safety.

Objective To investigate the mechanism of mitochondrial autophagy regulating the expression of NLRP3 inflammasome in prostate tissue in experimental autoimmune prostatitis(EAP)rats and to provide a theoretical basis for the study of new drug development.Methods A numerical table of 40 SD male rats was randomly divided into 8 groups.Namely,normal group(N),model group(M),rapamycin group(RAP),rapamycin+mitochondrial autophagy inhibitor group(RAP+Mdivi-1),autophagy inhibitor group(3MA),mitochondrial autophagy inhibitor group(Mdivi-1),Caspase1 inhibitor group(Caspase1),NLRP3 inhibitor group(NLRP3),5 animals per group.After drug intervention,HE staining,immunofluorescence,colorimetry,and WB method were used to observe the relevant indexes.Results Compared with group N,the structural damage of prostate gland was obvious in group M.Compared with the M group,the prostate gland structure in RAP group,Caspase-1 group and NLRP3 group were improved.However,that in 3-MA group and Mdivi-1 group was not improved,and even destroyed more obvi-ously.Compared with group N,the co-expression of LC3-II and LAMP-1 was enhanced,mitochondrial membrane potential was decreased,ROS release level was significantly increased in prostate tissue of rats in group M.Com-pared with the M group,the above indexes in RAP group and NLRP3 group were significantly improved.However,the above indexes in 3-MA group and Mdivi-1 group became worse.Compared with group N,the protein expressions of DRP1,PINK1 and Parkin in prostate mitochondria of rats in group M were increased,and the protein expres-sions of OPA1 was decreased.Compared with group M,the protein expressions of DRP1,PINK1 and Parkin in RAP group and NLRP3 group were significantly increased,while those in 3-MA group and Mdivi-1 group were sig-nificantly decreased.OPA1 protein expression was significantly decreased in the RAP group.The protein expression of Parkin in Caspase-1 group was decreased,but the protein expression of DRP1,OPA1 and PINK1 had no significant difference.Compared with group N,the protein expressions of LC3II/LC3I,Beclin1,NLRP3,ASC,Cleaced-Caspase1,Cleaced-IL-1β,and IL-18 in prostate tissue of rats in group M were increased,while the protein expres-sions of P62 was decreased.Compared with M group,LC3II/LC3I and Beclin1 protein expressions in RAP group and NLRP3 group were significantly increased,while those in 3-MA group and Mdivi-1 group were significantly decreased.Compared with M group,P62,NLRP3,ASC,Cleaced-Caspase1,Cleaced-IL-1β and IL-18 protein expressions in RAP group and NLRP3 group were significantly decreased,while those in 3-MA group and Mdivi-1 group were significantly increased.Compared with M group,the protein expressions of NLRP3,ASC,Cleaced-Caspase1,Cleaced-IL-1β,and IL-18 in Caspase-1 group were significantly reduced,but the protein expressions of LC3Ⅱ/LC3Ⅰ,Beclin1,and P62 were not statistically significant.Conclusions NLRP3 inflammatosome is involved in the progression of chronic prostatitis in EAP rats.Mitochondrial autophagy mediates the occurrence and development of prostatitis in EAP by regulating the activation of NLRP3 inflammasome in prostate tissue.

Objective The pathogenesis of EAP in rats based on the TLR4/NF-κB-NLRP3 inflammasome signaling pathway was explored.Methods Randomly divide 12 male SD rats into 4 groups using the number table,namely normal group(N),model group(M),Caspase-1 inhibitor group(Caspase-1),and NLRP3 inhibitor MCC950 group(NLRP3),with 3 rats in each group.After drug intervention,relevant indicators were observed by using HE staining,ELISA,WB methods.Results Compared with the N group,the M group rats had showed significant damage in prostate gland structure and infiltration of inflammatory cells.Compared with group N,the expression of TLR4,P-NF-κB P65,NLRP3,ASC,Cleaced-Caspase-1,Cleaced-IL-1β,and IL-18 proteins in the prostate tissue of group M rats had increased(P<0.01).Compared with group M,the expression of TLR4,P-NF-κB P65,NLRP3,ASC,Cleaced-Caspase-1,Cleaced-IL-1β,and IL-18 proteins in the NLRP3 and Caspase-1 groups had significantly reduced(P<0.01).The serum levels of IL-1 β,IL-6,IL-8,IL-17A,IL-18,IFN-γ,and TNF-α in group M rats had been significantly higher than those in group N(P<0.01).But the serum levels of IL-10 had been slightly lower and no statistical significance.The serum levels of IL-1β,IL-6,IL-8,IL-17A,IL-18,IFN-γ,and TNF-α in group M rats had been lower than those in group N(P<0.01 or P<0.05),the serum IL-10 level had increased(P<0.01).Conclusion The activation of TLR4/NF-κB-NLRP3 inflammasome signaling path-way promotes the occurrence and development of prostatitis in EAP rats.

A male patient,51 years old,was diagnosed as follows:① type 2 diabetes mellitus;② grade 2 hypertension(extremely high risk).To improve circulation,the patient was administered pentoxifylline injection 0.2 g mixed with 250 mL of 0.9％sodium chloride injection via an intravenous drip,once daily(qd).After 4 days of treatment,liver function tests showed the following results:alanine aminotransferase(ALT)at 2 390.80 U·L-1,aspartate aminotransferase(AST)at 948.28 U·L-1,and gamma-glutamyltransferase(GGT)at 517.81 U·L-1.It was highly probable that pentoxifylline caused abnormally elevated liver enzymes,with a clear drug-related association.After discontinuing pentoxifylline injection and initiating liver-protecting and en-zyme-lowering treatment,the liver function indicators gradually improved.Enhanced monitoring during the clinical use of pentoxi-fylline is essential to ensure patient safety.

Objective To investigate the mechanism of mitochondrial autophagy regulating the expression of NLRP3 inflammasome in prostate tissue in experimental autoimmune prostatitis(EAP)rats and to provide a theoretical basis for the study of new drug development.Methods A numerical table of 40 SD male rats was randomly divided into 8 groups.Namely,normal group(N),model group(M),rapamycin group(RAP),rapamycin+mitochondrial autophagy inhibitor group(RAP+Mdivi-1),autophagy inhibitor group(3MA),mitochondrial autophagy inhibitor group(Mdivi-1),Caspase1 inhibitor group(Caspase1),NLRP3 inhibitor group(NLRP3),5 animals per group.After drug intervention,HE staining,immunofluorescence,colorimetry,and WB method were used to observe the relevant indexes.Results Compared with group N,the structural damage of prostate gland was obvious in group M.Compared with the M group,the prostate gland structure in RAP group,Caspase-1 group and NLRP3 group were improved.However,that in 3-MA group and Mdivi-1 group was not improved,and even destroyed more obvi-ously.Compared with group N,the co-expression of LC3-II and LAMP-1 was enhanced,mitochondrial membrane potential was decreased,ROS release level was significantly increased in prostate tissue of rats in group M.Com-pared with the M group,the above indexes in RAP group and NLRP3 group were significantly improved.However,the above indexes in 3-MA group and Mdivi-1 group became worse.Compared with group N,the protein expressions of DRP1,PINK1 and Parkin in prostate mitochondria of rats in group M were increased,and the protein expres-sions of OPA1 was decreased.Compared with group M,the protein expressions of DRP1,PINK1 and Parkin in RAP group and NLRP3 group were significantly increased,while those in 3-MA group and Mdivi-1 group were sig-nificantly decreased.OPA1 protein expression was significantly decreased in the RAP group.The protein expression of Parkin in Caspase-1 group was decreased,but the protein expression of DRP1,OPA1 and PINK1 had no significant difference.Compared with group N,the protein expressions of LC3II/LC3I,Beclin1,NLRP3,ASC,Cleaced-Caspase1,Cleaced-IL-1β,and IL-18 in prostate tissue of rats in group M were increased,while the protein expres-sions of P62 was decreased.Compared with M group,LC3II/LC3I and Beclin1 protein expressions in RAP group and NLRP3 group were significantly increased,while those in 3-MA group and Mdivi-1 group were significantly decreased.Compared with M group,P62,NLRP3,ASC,Cleaced-Caspase1,Cleaced-IL-1β and IL-18 protein expressions in RAP group and NLRP3 group were significantly decreased,while those in 3-MA group and Mdivi-1 group were significantly increased.Compared with M group,the protein expressions of NLRP3,ASC,Cleaced-Caspase1,Cleaced-IL-1β,and IL-18 in Caspase-1 group were significantly reduced,but the protein expressions of LC3Ⅱ/LC3Ⅰ,Beclin1,and P62 were not statistically significant.Conclusions NLRP3 inflammatosome is involved in the progression of chronic prostatitis in EAP rats.Mitochondrial autophagy mediates the occurrence and development of prostatitis in EAP by regulating the activation of NLRP3 inflammasome in prostate tissue.

Objective To explore the safety and feasibility of the application of day surgery management model under enhanced recovery after surgery(ERAS)concept in patients undergoing gynecologic laparoscopic surgery.Methods A non-randomized concurrent control trial was conducted on the patients who underwent laparoscopic surgery in our department from January to August 2021.A total of 92 patients admitted on odd date were assigned into Ward B of our department and served as the control group,and another 96 patients hospitalized on even date were subjected into Ward A and served as the observation group.The control group was given the routine treatment schedule,including the relevant examinations after admission and general operation procedure during hospitalization.The observation group was under a day surgery management model based on the concept of ERAS,with aid of a day surgery team and optimized perioperative management measures,including pre-hospital rehabilitation,shortening water fasting before surgery,multi-mode analgesia,preventive antiemesis,intraoperative warmth,prevention of deep vein thrombosis,immediate postoperative eating and activity,and follow-up after discharge.Postoperative subjective comfort,intestinal function recovery,social and economic benefits,postoperative complications and inflammatory indicators were compared between the 2 groups.Results In 0～6,7～12 and 13～24 h after operation,the scores of thirst,hunger,nausea,pain,abdominal distension and pharyngeal discomfort were significantly lower in the observation group than the control group(P＜0.01).The observation group had obviously shorter length of hospital stay and ealier bowel sound recovery and first anal exhaust than the control group(P＜0.01).No postoperative complication,such as fall,unplanned secondary operation or wound infection was observed in both groups.The postoperative inflammatory indicators,including procalcitonin(PCT),neutrophil percentage(Neu％)and white blood cell count(WBC)were all in the normal ranges in the 2 groups at 24 h and 3 and 7 d after surgery.Statistical differences were found in firstly postoperative mobilization,length of hospital stay,hospitalization cost and patient satisfaction between the 2 groups(P＜0.01).Conclusion ERAS-based day surgery management model has the advantages of shortening hospital stay,reducing medical costs,promoting postoperative rehabilitation,and improving the comfort and satisfaction in patients undergoing gynecologic laparoscopic surgery.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

  Objective  This study aimed to investigate Chinese anesthesiologists' comprehension of palliative care and their experiences with palliative sedation for patients in the end-stage of life.  Methods  From October to December 2021, a national cross-sectional survey was conducted among anesthesiologists in China distributed by the Chinese Society of Anesthesiology, Chinese Medical Association with convenient sampling. The survey questionnaire encompassed general information, professional experience, familiarity with palliative care, emotional responses to end-stage cases, experience with sedation for critically ill or end-stage patients, and preferences for sedation medication.  Results  A total of 2536 anesthesiologists from 29 provinces in China completed valid questionnaires. Among them, 572 anesthesiologists(22.6%, 572/2536) reported familiarity with palliative medicine. Male anesthesiologists, as well as those with prior experience in caring for critically ill or end-stage patients, involved in pain management and practicing in hospitals with established institutional palliative care teams, demonstrated greater familiarity with palliative care concepts(all P<0.05). Over 40% of respondents felt powerless, helpless, and indecisive when confronted with end-stage patients. Anesthesiologists knowledgeable about palliative care exhibited greater confidence in managing critically ill or end-stage patients(9.8% vs. 4.4%, P=0.001). Among the anesthesiologists surveyed, 734 had administered sedation to end-stage patients, with 151 of them(20.6%, 151/734) inappropriately relying solely on opioids for sedation.  Conclusions  The understanding of palliative care and palliative sedation medication choice among anesthesiologists in China is still very limited. The establishment of palliative care teams, provision of education and training in palliative care, and enhancement of familiarity with palliative principles may bolster anesthesiologists' confidence when encountering critically ill or end-stage patients and subsequently enhance the quality of care for patients in the terminal stages of life.