Objective To investigate the feasibility of P16 immunohistochemistry combined with routine pathology in judging the residual lesion of high grade cervical intraepithelial neoplasia.Methods Patients with cervical conization for high grade cervical intrapithelial neoplasia in this hospital from January 2014 to May 2016 were chose and divided into P16 immunohistochemical detection combined with pathological diagnosis group and pathological evaluation group according to patient's motivation.Patients with residual margins were treated in accordance with the clinical guidelines and TCT was followed up for 6 months after no margin.Then sensitivity and accuracy of two group were analyzed by gold standard of follow-up results.Results 104 patients in P16 immunohistochemical detection combined with pathological diagnosis group were negative in TCT test after 6 month of following up after surgery.However,at the time of 6 months follow-up after surgery,7 patients of 112 patients have been diagnosed with positive by TCT in pathological evaluation group.The Sensitivity and accuracy in P16 immunohistochemical detection combined with pathological diagnosis group were 100％ which were higher than pathological evaluation group.Conclusion P16 immunohistochemical detection combined with conventional pathology can accurately diagnose the cervical cutting edge of conization.

Objective To analyze the relationship between methylenetetrahydrofolate reductase (MTHFR)C677T,A1298C and methionine synthase reductase(MTRR)gene polymorphism with abnormal pregnancy history.Methods 549 normal women (control group)and 300 women with the abnormal pregnancy history(observation group)were taken as the subjects by adopting the case control research method.The oral mucosa epithelial cells were collected for extracting genomic DNA.The MTHFR and MTRR gene polymorphisms were detected by the gene sequencing method.Results The distribution frequency of MTHFR 677TT genotype in the abnormal pregnancy group was significantly increased compared with the control group (10.00% vs.3.46%,χ2 =15.25,P <0.01);the distribution frequency of MTHFR-1298CC genotype in the abnormal pregnancy group was significantly in-creased compared with the control group (11.00 vs.4.01%,χ2 =15.66,P <0.01);the distribution frequency of MTRR A66G gen-otype had no statistical difference between the two groups(χ2 =3.02,P =0.082).The interactive analysis of 2 genes indicated that simultaneous carrying the MTHFR A1298C mutation site and MTRR A66G mutation site increased the possibility of abnormal pregnancy occurrence (OR=1.52,P =0.011).Conclusion MTHFR C677T and A1298C have a certain correlation with female ab-normal pregnancy occurrence.

Objective To investigate the experience of surgical treatment of primary extraperitoneal pelvic neoplasms,in order to improve tumor resection rate and safety.Methods The clinical data of 29 cases of primary extraperitoneal pelvic neoplasms were retrospectively analyzed from 1995 to 2013.To evaluate tumor resection preoperatively by CT,MRI and three dimensional reconstruction (3 d) medical technology,5 cases of preoperative interventional vascular embolization,intraoperative 2 cases in the iliac artery ligation,2 cases of intraoperative temporary blocking abdominal aorta.Intraoperative combined a variety of surgical approach to remove the tumor.Results Twenty-nine cases of patients,11 underwent tumor resection,5 underwent tumor resection and rectum resection plus sigmoid colostomy,the structure of 4 underwent tumor resection and repair damaged + sigmoid colon rectum temporary colostomy,3 underwent tumor resection and bladder partial nephrectomy,4 underwent tumor resection and uterine ovarian resection,2 underwent tumor resection + tail sacral tumor resection.25 patients recover well after the surgery,complications of 4 cases:intestinal obstruction in 2 cases respectively,pelvic abscess in 1 case,lower limb venous thrombosis in 1 case,cured by conservative and interventional therapy.No operative mortality and incidence of complications was 13.8％ (4/29).Conclusion Pelvic tumor preoperative imaging evaluation,combined incision and multi-visceral resection,fractional resection and recurrence after resection is the effective examination and treatment.

Objective To explore protective effects of curcumin on lung injury in the early hepatic ischemia/reperfsion (reperfusion for 1 and 3 hour) inrats. Methods Wistarratswererandom]y divided into the fo]]owinggroups: GroupA (shamoperation), group B (control group) and group C (cureumin applied). Contents of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO) in lung tissues were determined to evaluate the protective effect of eurcumin on lung injury in the injury of isehemia/ reperfusion. Results Curcumin relieved edema of diaphragmatic wall and exudation of blood cell and white cell in pulmonary alveoli. Curcumin increased the contents of SOD, CAT and decreased contents of MDA, MPO in lung tissue. Conclusion By repressing the generation of oxygen free radical and infiltration of polymorphonuclear leukocyte in lung tissue, curcumin can relieve lung injury in the early hepatic ischemia/repeffusion.

Objective: To explore clustering and risk factors of Staphylococcus aureus (S. aureus) carriage among kindergarten children in Liuzhou. Methods: Two sided nasal swabs were collected from 1 702 children in Liuzhou from April to June 2018. Parents of all the children were investigated by questionnaires. The random effect Logistic regression was used to analyze the clustering and risk factors of S. aureus carriage. Results: The carriage rate of S. aureus among kindergarten children was 16.3%. The randomeffect Logistic regression model indicated that the class-level random effect of S. aureus carriage among children was statistically significant(Z=2.12, P<0.01). Children aged 6 to 7 years (OR=2.18, 95%CI=1.45-3.27) and 5 years (OR=1.65, 95%CI=1.08-2.50) had higher carriage rates of S. aureus than those aged 3-4 years. The history of antibiotic using (OR=1.45, 95%CI=1.05-2.01) and skin and soft tissue infections (OR=1.36, 95%CI=1.04-1.79) in the previous year were risk factors of S. aureus carriage among children. Conclusion The class level clustering of S. aureus carriage is observed in healthy children. Age, history of antibiotic usage and history of skin and soft tissue infections are associated with risk of S. aureus carriage among preschool children.

Objective:To compare the efficacy and safety of programmed death-1(PD-1)inhibitors in combination with chemotherapy versus chemotherapy alone in patients with metastatic bladder cancer.Methods:A retrospective analysis was performed on the clinical data of 77 cases of metastatic bladder cancer who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to October 2022. According to the different clinical treatment regimens, they were divided into two groups. Patients treated with PD-1 inhibitors combined with gemcitabine and cisplatin (GC) regimen were referred to as IGC group, and patients who received GC chemotherapy alone were referred to as GC group. There were 24 cases in IGC group, including 18 males and 6 females, with a median age of 60 (56, 67) years old. Seventeen cases had a history of smoking. Fifteen cases had an Eastern Cooperative Oncology Group (ECOG) score of 0 and 9 cases had a score of 1. Twenty-three cases suffered distant metastasis (stage M 1). Two cases suffered lymph node metastasis only, 6 cases with liver metastasis, 8 cases with lung metastasis, and 8 cases with bone metastasis. There were 53 cases in GC group, including 45 males and 8 females, with a median age of 63 (55, 69) years old. Thirty-one cases had a history of smoking. Thirty cases had an ECOG score of 0 and 23 cases had a score of 1, 48 cases suffered stage M 1, 2 cases suffered lymph node metastasis only. Nineteen cases suffered liver metastasis. Twenty-seven cases suffered lung metastasis. And 23 cases suffered bone metastasis. There was no statistically significant difference in the above general information between the two groups ( P>0.05). Kaplan-Meier method was used to plot the survival curves, and the difference of median progression-free survival (mPFS) and median overall survival (mOS) between the two groups was compared by log-rank test. Finally, the difference in adverse reactions between the two groups was compared. Results:The objective response rate (ORR) was 41.7% and the disease control rate (DCR) was 87.5% in the IGC group.As a comparison, the ORR was 43.4% and the DCR was 83.0% in the GC group. The differences in ORR ( P=0.887) and DCR ( P=0.871) between the two groups were not statistically significant. All patients were followed up for 3 to 45 months, with a median follow-up time of 24 (14, 43) months. The mPFS was 7.0 (95% CI 5.7-8.3) months in the GC group and 8.0 (95% CI 3.0-13.1) months in the IGC group, and the difference was statistically significant between the two groups ( P=0.026). The mOS of patients in the GC group was 16.0 (95% CI 14.4-17.6) months, the mOS was not yet reached in the IGC group, and patients in the IGC group had longer mOS with a statistically significant difference ( P=0.022). All patients experienced treatment-related adverse reactions. Grade 3-4 adverse reactions occurred in 8 cases (33.3%) in the IGC group and in 16 cases (30.2%) in the GC group, and no adverse reaction-related deaths were observed( P=0.992). The most common adverse reactions in both groups were anemia, including 18 cases (75.0%) in IGC group and 38 cases (71.7%) in GC group. There were 4 cases (16.7%) of grade 1-2 hypothyroidism in the IGC group but no patients with hypothyroidism were found in the GC group, and the difference was statistically significant ( P=0.012). There were 8 cases (33.3%) and 4 cases (7.5%) of grade 1-2 skin adverse reactions in the IGC and GC groups, respectively, and the difference was statistically significant ( P=0.011). The immune-related adverse reactions of PD-1 inhibitors in IGC group were 1 case of hyperthyroidism (4.2%), 4 cases of hypothyroidism (16.7%), 1 case of adrenal insufficiency (4.2%), and 1 case of immune colitis (4.2%). Conclusions:Compared with chemotherapy alone, PD-1 inhibitors combined with chemotherapy for metastatic bladder cancer can effectively prolong the mPFS and median mOS. The adverse reactions of the two groups were tolerable, and there was no significant difference in the incidence of grade 3-4 adverse reactions. In general, PD-1 inhibitors combined with chemotherapy in the treatment of metastatic bladder cancer is safe and feasible, but attention should be paid to the immune-related adverse reactions of PD-1 inhibitors.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation