Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report.

BACKGROUND: Breast cancer brain metastasis (BCBM) is an advanced breast disease that is difficult to treat and is associated with a high risk of death. Patient prognosis is usually poor, with reduced quality of life. In this context, we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb (inetetamab) combined with a small molecule tyrosine kinase inhibitor (TKI). CASE SUMMARY: The patient was a 58-year-old woman with a 12-year history of type 2 diabetes. She was compliant with regular insulin treatment and had good blood glucose control. The patient was diagnosed with invasive carcinoma of the right breast (T3N1M0 stage IIIa, HER2-positive type) through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019. Immunohistochemistry showed ER (-), PR (-), HER-2 (3+), and Ki-67 (55-60%+). Preoperative neoadjuvant chemotherapy, i.e., the AC-TH regimen (epirubicin, cyclophosphamide, docetaxel-paclitaxel, and trastuzumab), was administered for 8 cycles. She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year. Brain metastasis was found 9 mo after surgery. She underwent brain metastasectomy in August 2020. Immunohistochemistry showed ER (-) and PR. (-), HER-2 (3+), and Ki-67 (10-20%+). In November 2020, the patient experienced headache symptoms. After an examination, tumor recurrence in the original surgical region of the brain was observed, and the patient was treated with inetetamab, pyrotinib, and capecitabine. Whole-brain radiotherapy was recommended. The patient and her family refused radiotherapy for personal reasons. In September 2021, a routine examination revealed that the brain tumor was considerably larger. The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases, followed by regular hospitalization and routine examinations. The patient's condition is generally stable, and she has a relatively high quality of life. This case report demonstrates that in patients with BCBM and resistance to trastuzumab, inetetamab combined with pyrotinib and chemotherapy can prolong survival. CONCLUSION: Inetetamab combined with small molecule TKI drugs, chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

High expression of long noncoding RNA plasmacytoma variant translocation 1 is an independent risk factor for recurrence after radiofrequency ablation in atrial fibrillation patients.

Atrial fibrillation (AF) is a common arrhythmia. Radiofrequency ablation (RFA) is the major AF treatment. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is related to AF diagnosis. This study explored the clinical roles of PVT1 in AF. Totally, 168 AF patients and 100 healthy controls were selected. Plasma lncRNA PVT1 in AF patients before/after RFA was detected and the diagnostic efficacy and postoperative recurrence prediction value in AF were analyzed. Effects of plasma PVT1 expression on AF recurrence and its correlation with transforming growth factor beta 1 (TGF-ß1) in the recurrence and non-recurrence groups were analyzed by Pearson coefficient. The risk factors of AF recurrence were evaluated. Plasma PVT1 was highly expressed in AF patients and diminished after RFA. PVT1 level >1.255 assisted AF diagnosis. The plasma PVT1 level in the recurrence group was higher than that of the non-recurrence group. PVT1 level >1.525 assisted the prediction for postoperative recurrence. AF postoperative recurrence incidence in high PVT1 expression group was clearly higher than that in low PVT1 expression group, and plasma PVT1 expression in patients of the recurrence and non-recurrence groups was positively correlated with TGF-ß1 content. High PVT1 expression was an independent risk factor for postoperative recurrence. Briefly, high PVT1 level assisted AF diagnosis and recurrence evaluation after RFA and was an independent risk factor for AF postoperative recurrence.

Multi-omics characterization of the unsaturated fatty acid biosynthesis pathway in colon cancer.

The biosynthesis of unsaturated fatty acids is involved in the initiation and progression of colon adenocarcinoma (COAD). In this study, we aimed to investigate the multi-omics characteristics of unsaturated fatty acid biosynthesis-related genes and explore their prognostic value in colon cancer by analyzing the data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. An unsaturated fatty acid biosynthesis pathway related-genes enrichment score (BUFAS) was constructed utilizing the single sample gene set enrichment analysis (ssGSEA). We discovered that a high BUFAS was associated with longer overall survival (OS) in both the training and the validation sets. Multivariable analysis including the clinical characteristics further verified the independent prognostic value of the BUFAS in both the TCGA-COAD and the GSE39582 datasets. In addition, GSEA analysis revealed that BUFAS was positively associated with several signaling pathways, including MTORC1, peroxisome, and pathways related to fatty acid metabolism, while was negatively associated with other signaling pathways, such as hedgehog, NOTCH, and Wnt/beta-catenin pathway. Furthermore, in the COAD cell lines of the Genomics of Drug Sensitivity in Cancer (GDSC) database, we found that BUFAS was positively correlated with the drug sensitivities of cisplatin, gemcitabine, camptothecin, lapatinib, and afatinib, while was negatively correlated with that of ponatinib. Moreover, in the COAD single-cell transcriptomic dataset (GSE146771), the BUFAS varied among different cell types and was enriched in mast cells and fibroblasts. Taken together, the BUFAS we constructed could be used as an independent prognostic signature in predicting the OS and drug resistance of colon cancer. Unsaturated fatty acid biosynthesis pathway might serve as potential therapeutic targets for cancer treatment.

Machine learning to predict high-dose methotrexate-related neutropenia and fever in children with B-cell acute lymphoblastic leukemia.

Methotrexate (MTX), an antimetabolite for the treatment of leukemia, could cause neutropenia and subsequently fever, which might lead to treatment delay and affect prognosis. Here, we aimed to predict neutropenia and fever related to high-dose MTX using artificial intelligence. This study included 139 pediatric patients newly diagnosed with standard- or intermediate risk B-cell acute lymphoblastic leukemia. Fifty-seven SNPs of 16 genes were genotyped. Univariate and multivariate analysis were used to select SNPs and clinical covariates for model developing. Five machine learning algorithms combined with four resampling techniques were used to build optimal predictive model. The combination of random forest with adaptive synthetic appeared to be the best model for neutropenia (sensitivity = 0.935, specificity = 0.920, AUC = 0.927) and performed best for fever (sensitivity = 0.818, specificity = 0.924, AUC = 0.870). By machine learning, we have developed and validated comprehensive models to predict the risk of neutropenia and fever. Such models may be helpful for medical oncologists in quick decision-making.

Effect of low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy: a prospective randomized trial.

BACKROUND: At present, low-concentration carbohydrate is rarely used in minor trauma surgery, and its clinical efficacy is unknown. The aim of the study was to evaluate the effect of preoperative oral low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy using Quality of Recovery - 15 (QoR-15) questionnaire. METHODS: One hundred twenty patients were randomized to oral intake of 300 ml carbohydrate solution (CH group) or 300 ml pure water (PW group) 2 h before surgery or fasting for 8 h before surgery (F group). The QoR-15 questionnaire was administered to compare the quality of recovery at 1d before surgery (T0), 24 h, 48 h, 72 h after surgery (T1, T2, T3), and perioperative blood glucose was recorded. RESULTS: Compared to the F group, the QoR-15 scores were statistically higher in the CH and PW group at T1 (P < 0.05), and the enhancement of recovery quality reached the clinical significance at T1 in the CH group compared with the F group. Among the five dimensions of the QoR-15 questionnaire, physical comfort, physiological support and emotional dimension in the CH group were significantly better than the F group (P < 0.05) at T1. Besides, blood glucose of CH group was significantly lower than the PW group and F group at each time point after surgery. CONCLUSIONS: Low-concentration carbohydrate could decrease the incidence of postoperative hyperglycemia and improve the patient-centered quality of recovery on patients undergoing open thyroidectomy at the early stage postoperatively. TRIAL REGISTRATION: ChiCTR1900024731 . Date of registration: 25/07/2019.

A Comprehensive Comparison Between the Semi-sterile and Sterile Technique for Closed Reduction and Percutaneous Pinning of Pediatric Supracondylar Humerus Fractures.

Background: Supracondylar humerus fracture is the most common elbow fracture in children, which often requires closed reduction and percutaneous pinning (CRPP) procedure for full recovery. In addition to the traditional sterile technique with full prep and draping, the semi-sterile technique without sterile gowns and drapes has been suggested to be a viable alternative for CRPP. Methods: Here, we performed a retrospective study over a 3-year period to comprehensively evaluate the outcomes of the semi-sterile and the sterile techniques for CRPP in supracondylar humerus fractured patients. Demographic data, fracture type, nerve injury status and the type of preparation technique (semi-sterile vs. sterile) were recorded. Time of preparation and operation, costs and elbow recovery status were compared. Outcomes of the two techniques were compared with bivariate analysis. Results: In a total of 137 patients, we found that the semi-sterile technique could significantly reduce the total operation room usage time (80 ± 13 min vs. 94 ± 12 min, 15% reduction, P < 0.001) and costs of CRPP. Specifically, anesthesia and medical waste costs were reduced by 139 RMB (1,736 ± 128 vs. 1,875 ± 197, 7.4% reduction, P < 0.001) and 103.0 RMB (14.6 vs. 117.9) per operation, respectively. At the meantime, the infection rate and recovery efficiency (89 ± 10 vs. 91 ± 9 of the Mayo Elbow Performance Score, P = 0.352) were almost unchanged as compared to the sterile technique group. Conclusions: Our study suggests that the semi-sterile technique can be used as a cost-effective alternative for CRPP in supracondylar humerus fracture and even other bone-related non-surgical approaches. Level of Evidence: The present study is a retrospective cohort study with a level III of evidence.

The tumor immune microenvironment transcriptomic subtypes of colorectal cancer for prognosis and development of precise immunotherapy.

BACKGROUND: Biomarkers based on immune context may guide prognosis prediction. T-cell inactivation, exclusion, or dysfunction could cause unfavorable tumor microenvironments, which affect immunotherapy and prognosis. However, none of the immuno-biomarkers reported to date can differentiate colorectal-cancer (CRC) patients. Thus, we aimed to classify CRC patients according to the levels of T-cell activation, exclusion, and dysfunction in the tumor microenvironment. METHODS: RNAseq data of 618 CRC patients from The Cancer Genome Atlas and microarray data of 316 CRC patients from Gene Expression Omnibus were analysed using the Tumor Immune Dysfunction and Exclusion algorithm. Unsupervised clustering was used to classify patients. RESULTS: Based on the expression signatures of myeloid-derived suppressor cells, cancer-associated fibroblasts, M2-like tumor-associated macrophages, cytotoxic T-lymphocytes, and PD-L1, all patients were clustered into four subtypes: cluster 1 had a high level of immune dysfunction, cluster 2 had a low level of immune activation, cluster 3 had intense immune exclusion, and cluster 4 had a high level of immune activation and a moderate level of both dysfunction and exclusion signatures. Compared with cluster 1, the hazard ratios and 95% confidential intervals for overall survival were 0.63 (0.35-1.13) for cluster 2, 0.55 (0.29-1.03) for cluster 3, and 0.30 (0.14-0.64) for cluster 4 in multivariate Cox regression. Similar immune clustering and prognosis patterns were obtained upon validation in the GSE39582 cohort. In subgroup analysis, immune clustering was significantly associated with overall survival among stage I/II patients, microsatellite stable/instability-low patients, and patients not treated with adjuvant therapy. CONCLUSIONS: Our findings demonstrated that classifying CRC patients into different immune subtypes serves as a reliable prognosis predictor and may help to refine patient selection for personalized cancer immunotherapy.

Antinociceptive effects of magnesium sulfate for monitored anesthesia care during hysteroscopy: a randomized controlled study.

BACKGROUND: Opioids are the most effective antinociceptive agents, they have undesirable side effects such as respiratory depressant and postoperative nausea and vomiting. The purpose of the study was to evaluate the antinociceptive efficacy of adjuvant magnesium sulphate to reduce intraoperative and postoperative opioids requirements and their related side effects during hysteroscopy. METHODS: Seventy patients scheduled for hysteroscopy were randomly divided into 2 groups. Patients in the magnesium group (Group M) received intravenous magnesium sulfate 50 mg/kg in 100 ml of isotonic saline over 15 min before anesthesia induction and then 15 mg/kg per hour by continuous intravenous infusion. Patients in the control group (Group C) received an equal volume of isotonic saline as placebo. All patients were anesthetized under a BIS guided monitored anesthesia care with propofol and fentanyl. Intraoperative hemodynamic variables were recorded and postoperative pain scores were assessed with verbal numerical rating scale (VNRS) 1 min, 15 min, 30 min, 1 h, and 4 h after recovery of consciousness. The primary outcome of our study was total amount of intraoperative and postoperative analgesics administered. RESULTS: Postoperative serum magnesium concentrations in Group C were significantly decreased than preoperative levels (0.86 ± 0.06 to 0.80 ± 0.08 mmol/L, P = 0.001) while there was no statistical change in Group M (0.86 ± 0.07 to 0.89 ± 0.07 mmol/L, P = 0.129). Bradycardia did not occur in either group and the incidence of hypotension was comparable between the two groups. Total dose of fentanyl given to patients in Group M was less than the one administered to Group C [100 (75-150) vs 145 (75-175) µg, median (range); P < 0.001]. In addition, patients receiving magnesium displayed lower VNRS scores at 15 min, 30 min, 1 h, and 4 h postoperatively. CONCLUSIONS: In hysteroscopy, adjuvant magnesium administration is beneficial to reduce intraoperative fentanyl requirement and postoperative pain without cardiovascular side effects. Our study indicates that if surgical patients have risk factors for hypomagnesemia, assessing and correcting magnesium level will be necessary. TRIAL REGISTRATION: ChiCTR1900024596 . date of registration: July 18th 2019.

Effects of epidural combined with general anesthesia versus general anesthesia on quality of recovery of elderly patients undergoing laparoscopic radical resection of colorectal cancer: A prospective randomized trial.

STUDY OBJECTIVES: The aim of the present study was to assess the quality of recovery from anesthesia on patients subjected to laparoscopic radical resection of colorectal cancer under epidural block combined with general anesthesia or general anesthesia by means of Quality of Recovery-15 (QoR-15) questionnaire. DESIGN: Prospective randomized trial. SETTING: The setting is at an operating room, a post-anesthesia care unit, and a hospital ward. PATIENTS: Seventy patients, aging from 65 to 79 years with an American Society of Anesthesiologists physical status II or III, were scheduled to undergo laparoscopic radical resection of colorectal cancer. INTERVENTIONS: Epidural block combined with general anesthesia or general anesthesia. MEASUREMENTS: The QoR-15 was administered by an investigator blind to group allocation before surgery (T0), at 24 and 72h after surgery (T1 and T2), and on postoperative day 7 (T3). The quality of recovery, as assessed by the score on the QoR-15, was compared between the groups. Besides, the consumption of anesthetics, respiratory recovery time, response time, extubation time, flatus time, the incidence of nausea or vomiting, the consumption of antiemetic and analgesic agents, and the duration of the hospital stay were also recorded. MAIN RESULTS: The QoR-15 scores at T1 and T2 were significantly higher in the E + G group compared with the G group (P < 0.05). Among the five dimensions of the QoR-15, physiological comfort, physiological independence, pain, and emotional dimension were significantly better at T1 in the E + G group, and physiological comfort and pain were significantly better at T2 in the E + G group. CONCLUSION: This study demonstrates that epidural block combined with general anesthesia can improve the early recovery of elderly patients after laparoscopic radical resection of colorectal cancer from the perspective of patients.

Corrigendum: A Comprehensive Comparison Between the Semi-sterile and Sterile Technique for Closed Reduction and Percutaneous Pinning of Pediatric Supracondylar Humerus Fractures.

[This corrects the article DOI: 10.3389/fsurg.2020.594027.].

Depth of Response was Associated with Progression-Free Survival in Patients with Advanced Non-small Cell Lung Cancer treated with EGFR-TKI.

Background: Response Evaluation Criteria in Solid Tumors (RECIST) has been widely utilized to evaluate new therapeutic strategies in cancer. However, RECIST fails to assess the heterogeneity of response in highly active therapies. Depth of response (DepOR), defined as the maximum percentage change in tumor size compared with baseline, may provide a new strategy to evaluate disease response. In the present study, we studied the association between DepOR and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Methods: Advanced NSCLC patients harboring EGFR driver mutation (L858R or exon 19 deletion) treated with EGFR-TKI from August 2014 to July 2017 from two sites were retrospetively collected for analysis. Patients were divided into four groups by DepOR (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, Q4 = 76-100%). Kaplan-Meier curves were plotted for PFS against DepOR and the hazard ratio (HR) was determined through univariable and multivariable cox regression models. Results: In total, 265 patients were included for analysis. The number of patients in Group Q1-Q4 were 91 (34.3%), 73 (27.5%), 65 (24.5%) and 36 (13.6%), respectively. A greater DepOR was significantly associated with a longer PFS (Log-rank P<0.0001). The HRs (95% CI) for PFS comparing patients with different DepOR status were 0.58 (0.42-0.80) for Q2, 0.49 (0.35-0.69) for Q3, and 0.33 (0.22-0.50) for Q4, all compared with patients in Q1. DepOR as a continuous variable was also associated with prolonged PFS (HR, 0.20; 95% CI, 0.13-0.33; P<0.001). Additionally, in the multivariable cox regression model, abnormal LDH, brain metastasis and male were found to be associated with worse PFS outcomes (P<0.05). Conclusion: A greater DepOR is significantly associated with PFS benefit in advanced NSCLC treated with EGFR-TKI, suggesting that it may be a useful clinical outcome to evaluate the response of targeted therapy.

Scar overlapping suture for treating chronic tendinous mallet finger in children.

PURPOSE: To evaluate the effect of scar overlapping suture for treating chronic tendinous mallet finger deformity in children. METHODS: Six patients younger than 18 years were investigated retrospectively. The active extensor lags of the distal interphalangeal joint (DIPJ) were all more than 40°, and the passive ranges of DIPJ motion were normal. They were all treated surgically by scar overlapping suture technique, featuring careful overlapping suture of the extensor scar and temporary transarticular Kirschner wire fixation of the DIPJ. RESULTS: Average follow-up was 3.1 years (ranging from 2 to 5 years). All patients made significant improvement in DIPJ activity. Three patients achieved full active DIPJ extension, whereas one patient had a 10° extensor lag and two patients had 5° extensor lags. All patients achieved normal active flexion ranges and full passive motion ranges of DIPJ compared with their uninjured side. There was no bone dysplasia, pain, or deformity recurrence. CONCLUSIONS: Scar overlapping suture for treating chronic tendinous mallet finger in children is safe and effective. According to the Crawford criteria, all patients were graded as excellent.

Repeated inhalation of sevoflurane inhibits the information transmission of Purkinje cells and delays motor development via the GABAA receptor ε subunit in neonatal mice.

General anesthesia is widely used in pediatric surgery, although the influence of general anesthesia on cerebellar information transmission and motor function is unclear. In the present study, neonatal mice received repeated inhalation of sevoflurane, and electrophysiological alterations in Purkinje cells (PCs) and the development of motor functions were detected. In addition, γ­aminobutyric acidA receptor ε (GABAA­R ε) subunit knockout mice were used to investigate the mechanism of action of sevoflurane on cerebellar function. In the neonatal mice, the field potential response of PCs induced by sensory stimulation and the motor function indices were markedly inhibited by sevoflurane, and the inhibitory effect was positively associated with the number of repetitions of anesthesia. In additional the GABAA­R ε subunit level of PCs was promoted by sevoflurane in a dose­dependent manner, and the inhibitory effects of sevoflurane on PC field potential response and motor function were alleviated in GABAA­R ε subunit knockout mice. The GABAA­R ε subunit was activated by sevoflurane, leading to inhibition of sensory information transmission in the cerebellar cortex, field potential responses of PCs and the development of cerebellar motor function. The present study provided experimental evidence for the safe usage of sevoflurane in clinical anesthesia, and suggested that GABAA­R ε subunit antagonists may be considered for combined application with general anesthesia with repeated inhalation of sevoflurane, for adverse effect prevention in the clinic.

MiR-34b/c rs4938723 Polymorphism Significantly Decreases the Risk of Digestive Tract Cancer: Meta-analysis.

BACKGROUND: Previous studies investigating the association between miR-34b/c rs4938723 polymorphism and cancer risk showed inconclusive. Here, we performed meta-analysis to investigate the association between miR- 34b/c rs4938723 polymorphism and digestive cancer risk. MATERIALS AND METHODS: Literature database including PubMed, OVID, Chinese National Knowledge Infrastructure (CNKI) were searched for publications concerning the association between the miR-34b/c rs4938723 polymorphism and digestive cancer risk. RESULTS: A total of 6 studies consisting of 3246 cases and 3568 controls were included in this meta-analysis. The combined analysis suggested the miR-34b/c rs4938723 polymorphism significantly reduced digestive cancer risk under allelic model, homogeneous co-dominant model and recessive model (C vs T: OR=0.88, 95%CI=0.82-0.95, p-value=0.001; CC vs TT: OR =0.67, 95%CI=0.57-0.80, p-value=0.000; CC vs TT/TC: OR=0.68, 95%CI=0.58-0.80, p-value=0.000). Q-test and I2 test revealed no significant heterogeneity in all genotype comparisons. The Begger's funnel plot and Egger's test did not show significant publication bias. CONCLUSIONS: The current evidence supports the conclusion that the miR-34b/c rs4938723 polymorphism decreases an individual's susceptibility to digestive cancers.

Ox-LDL induces dysfunction of endothelial progenitor cells via activation of NF-κB.

Dyslipidemia increases the risks for atherosclerosis in part by impairing endothelial integrity. Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. Oxidized low-density lipoprotein (ox-LDL) can induce EPC dysfunction, but the underlying mechanism is not well understood. Human EPCs were cultured in endothelial growth medium supplemented with VEGF (10 ng/mL) and bFGF (10 ng/mL). The cells were treated with ox-LDL (50 µg/mL). EPC proliferation was assayed by using CCK8 kits. Expression and translocation of nuclear factor-kabba B (NF-κB) were evaluated. The level of reactive oxygen species (ROS) in cells was measured using H2DCF-DA as a fluorescence probe. The activity of NADPH oxidase activity was determined by colorimetric assay. Ox-LDL significantly decreased the proliferation, migration, and adhesion capacity of EPCs, while significantly increased ROS production and NADPH oxidase expression. Ox-LDL induced NF-κB P65 mRNA expression and translocation in EPCs. Thus ox-LDL can induce EPC dysfunction at least by increasing expression and translocation of NF-κB P65 and NADPH oxidase activity, which represents a new mechanism of lipidemia-induced vascular injury.

Effect of the combined probiotics with aflatoxin B1-degrading enzyme on aflatoxin detoxification, broiler production performance and hepatic enzyme gene expression.

In order to degrade aflatoxin B1 (AFB1), AFB1-degrading microbes (probiotics) such as Lactobacillus casei, Bacillus subtilis and Pichia anomala, and the AFB1-degrading enzyme from Aspergillus oryzae were selected and combined to make feed additive. Seventy-five 43-day-old male Arbor Acres broilers were randomly divided into 5 groups, 15 broilers for each group. The broilers were given with 5 kinds of diets such as the basal diet, 400 µg/kg AFB1 supplement without feed additive, and 200, 400, 800 µg/kg AFB1 supplement with 0.15% feed additive. The feeding experimental period was 30 d, which was used to determine production performance of broilers. In addition, serum, liver and chest muscle were selected for measuring AFB1 residues, gene expressions, microscopic and antioxidant analyses. The results showed that adding 0.15% feed additive in broiler diets could significantly relieve the negative effect of AFB1 on chicken's production performance and nutrient metabolic rates (P<0.05). It could also improve AFB1 metabolism, hepatic cell structure, antioxidant activity, and many hepatic enzyme gene expressions involved in oxidoreductase, apoptosis, cell growth, immune system and metabolic process (P<0.05). It could be concluded that the feed additive was able to degrade AFB1 and improve animal production.

[A meta-analysis on short and long term efficacy and safety of procedure for prolapse and hemorrhoids].

OBJECTIVE: To Systematic review and meta-analysis of short and long term efficacy and safety of procedure for prolapse and hemorrhoids. METHODS: Electronic databases including Cochrane Library, PubMed, OVID, SpringerLinker, ScinceDirect, EBSCO, CNKI, VIP, WanFang Data and CBM were searched. The date of search was between January 2000 and January 2013. Randomized controlled trials (RCTs) were indentified studying association of Compare PPH and Milligan-Mogan (MMH) treatment. Study selection and meta-analysis were conducted according to the Cochrane Handbook for RevMan 5.1 software. RESULTS: The trials involving 1343 patients were included. The results of meta-analysis indicated: compared with MMH, PPH operative time (OR = -11.05, 95%CI: -15.15--6.95, P < 0.01), duration of hospitalization (OR = -3.07, 95%CI: -4.46--1.69, P < 0.01) and return to normal activity time (OR = -7.17, 95%CI: - 9.13--5.20, P < 0.01) was short, postoperative pain light (OR = -3.13, 95%CI: -4.38--1.88, P < 0.01), but the high cost of treatment (OR = 2534.2, 95%CI: 509.0-4559.4, P = 0.01). Long-term efficacy, PPH was higher patient satisfaction (OR = 2.21, 95%CI: 1.03-4.75, P = 0.04), but the recurrence rate of prolapse (OR = 3.75, 95%CI: 1.75-8.06, P < 0.01) and reoperation rate (OR = 7.90, 95%CI: 1.78-35.03, P < 0.01) higher. The incidence of anal stenosis and anal incontinence postoperative were higher than MMH (P > 0.05). The difference of post operative anal stenosis and anal incontinence and residual skin tag rate were not statistically significant (all P > 0.05). CONCLUSIONS: PPH surgery can be used as replacement therapy of MMH for III°-IV° prolapsed hemorrhoids. But we should inform patients of prolapse recurrence and reoperation risk of PPH in the long term.

Part IV: Design, synthesis and antitumor activity of fluoroquinolone C-3 heterocycles: bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin.

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).