[Application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection in the sphincter-preserving resection of low rectal cancer].

Objectives: To investigate the application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection (LDER) in the anal preservation treatment of low rectal cancer. Methods: Inclusion criteria: (1) age was 18-70; (2) the distance of the lower tumor edge from the anal verge was 4-5 cm; (3) primary tumor with a diameter ≤3 cm; (4) preoperative staging of T1~2N1~2M0; (5) "difficult pelvis", defined as ischial tuberosity diameter<10 cm or body mass index>25 kg/m2; (6) patients with strong intention for sphincter preservation; (7) no preoperative treatment (e.g., chemotherapy, radiotherapy, molecular targeted therapy, or immunotherapy); (8) no lateral lymph node enlargement; (9) no previous anorectal surgery; (10) patients with good basic condition who could tolerate surgery. Exclusion criteria: (1) previously suffered from malignant tumors of the digestive tract or currently suffering from malignant tumors out of the digestive tract; (2) patients with preoperative anal dysfunction (Wexner score ≥ 10), or fecal incontinence. The specific surgical steps are as follows: the distal end of the rectum was dissected to the level of the interspace between internal and external sphincters of anal canal. Five centimeters proximal to the tumor, the mesorectum was ligated, and a liner stapler was used to transect the rectum. The distal rectum with the tumor were then everted and extracted through the anus. The rectum was transected 0.5-1.0 cm distal to the tumor with a linear stapler. Full thickness suture was used to reinforce the stump of the rectum, which was then brought back into the pelvic cavity. Finally, an end-to-end anastomosis between the colon and the rectum was performed. A retrospective descriptive study was performed of the clinical and pathological data of 12 patients with T1-T2 stage low rectal cancer treated with LDER at Henan Provincial People's Hospital from January 2020 to December 2022. Results: All 12 patients successfully completed LDER with sphincter preservation, without conversion to open surgery or changes in surgical approach. The median surgical time was 272 (155-320) minutes, with a median bleeding volume of 100 (50-200) mL. No protective stoma was performed, and all patients received R0 resection. The average hospital stay was 9 (7-15) days. There were no postoperative anastomotic leakage or perioperative deaths. All 12 patients received postoperative follow-up, with a median follow-up of 12 months (6-36 months) and a Wexner score of 8 (5-14) at 6 months postoperatively. There was no tumor recurrence or metastasis during the follow-up period. Conclusions: LDER is safe and effective for the treatment of low rectal cancer.

Effectiveness of systemic treatments for pyoderma gangrenosum: a systematic review of observational studies and clinical trials.

BACKGROUND: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis with substantial morbidity. There is no consensus on gold-standard treatments. OBJECTIVES: To review the effectiveness of systemic therapy for PG. METHODS: We searched six databases for 24 systemic therapies for PG. Primary outcomes were complete healing and clinical improvement; secondary outcomes were time to healing and adverse effects. RESULTS: We found 3326 citations and 375 articles underwent full-text review; 41 studies met the inclusion criteria. There were 704 participants in 26 retrospective cohort studies, three prospective cohort studies, seven case series, one case-control study, two open-label trials and two randomized controlled trials (RCTs). Systemic corticosteroids were the most studied (32 studies), followed by ciclosporin (21 studies), biologics (16 studies) and oral dapsone (11 studies). One RCT (STOP-GAP, n = 121) showed that prednisolone and ciclosporin were similar: 15-20% of patients showed complete healing at 6 weeks and 47% at 6 months. Another RCT (n = 30) found that infliximab was superior to placebo at 2 weeks (46% vs. 6% response), with a 21% complete healing rate at 6 weeks. Two uncontrolled trials showed 60% and 37% healing within 4 months for canakinumab and infliximab, respectively; other data suggest that patients with concurrent inflammatory bowel disease may benefit from biologics. The remaining studies were poor quality and had small sample sizes but supported the use of corticosteroids, ciclosporin and biologics. CONCLUSIONS: Systemic corticosteroids, ciclosporin, infliximab and canakinumab had the most evidence in treating PG. However, current literature is limited to small and lower-quality studies with substantial heterogeneity.

The zinc-finger transcriptional factor Slug transcriptionally downregulates ERα by recruiting lysine-specific demethylase 1 in human breast cancer.

Estrogen receptor α (ERα) is related with epithelial-mesenchymal transition, invasion and metastasis, and serves as an important therapeutic predictor and prognostic factor in breast cancer patients. The triple negative breast cancer (TNBC) is characterized by loss of hormone receptors and human epidermal growth factor receptor 2 (Her2), and lacks effective targeted therapy with poor prognosis. Unfortunately, the molecular mechanisms of ERα deficiency, which becomes hormone independent and results in resistance to endocrine therapy, remain to be elucidated in breast cancer. In this study, we observed an inverse correlation between Slug, a zinc-finger transcriptional repressor, and ERα expression in both human breast cancer tissues and cell lines. In ERα-negative breast cancer patients, high Slug messenger RNA expression showed obviously shorter relapse-free survival. We found that Slug binds to the E-box located in the promoter of estrogen receptor 1 gene (ESR1) to suppress its expression. More specifically, Slug recruits lysine-specific demethylase 1 (LSD1) to the E-box and thereby inhibits ERα expression by demethylating H3K4me2, which is evidenced by the interaction between Slug and LSD1. Moreover, the amount of H3K4me2 binding to the E-box was significantly increased after LSD1 knockdown in MDA-MB-231 cells. Functionally, the ability to proliferate, invade and metastasize was significantly suppressed after knockdown of either Slug or LSD1 alone, or both simultaneously. Taken together, these results suggest that Slug transcriptionally inhibits ERα expression by recruiting LSD1 to the ESR1 promoter in breast cancers. Thus, targeted inhibition of Slug and LSD1 may restore ERα and lead to resensitization to hormone therapy, providing a novel therapeutic strategy for ERα-negative breast cancer patients, especially for TNBC.

Asthma-COPD overlap syndrome showed more exacerbations however lower mortality than COPD.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is a new determinate syndrome whose exact characteristics remain unclear. AIM: The objective of this study is to find more difference between ACOS and COPD. DESIGN: A retrospective study of ACOS and COPD in Chinese. METHODS: Data from 65 patients with ACOS and 65 patients with COPD were retrospectively collected and analyzed. The basis of this study was to compare the two groups while ruling out differences in age, sex and smoking history. RESULTS: Patients with ACOS tended to have earlier ages of onset, longer durations of symptoms, better nutritional status, higher single-breath diffusing capacity of carbon monoxide (DLCO) %predicted and airway resistance %predicted, more exacerbations in the preceding 12 months and shorter lengths of hospitalization. DLCO %predicted, airway resistance %predicted, and length of hospitalization were the variables most significantly associated with the presence of ACOS in patients with COPD. ROC correlating airway resistance %predicted value and current ACOS showed an optimal cutoff of airway resistance %predicted of over 296.6. During follow-up (median: 45 months; interquartile range: 6-82 months), 16 patient deaths were recorded (3 patients with ACOS). The risk remained significantly higher in patients with COPD alone than in patients with ACOS (HR 3.932; 95% CI 1.083-19.755; P = 0.046). CONCLUSION: Patients with ACOS were more likely to have better prognoses and lower mortality than those with COPD alone, though with greater exacerbation frequency.

The prevalence of anxiety in patients with psoriasis: a systematic review of observational studies and clinical trials.

Psoriasis and anxiety are chronic conditions with significant morbidity and there is evidence that they may exacerbate one another. There is little data on the prevalence of anxiety in psoriasis and the effect of psoriasis treatment on comorbid anxiety. The objective of this study was to perform a systematic review of the literature to describe the prevalence and severity of clinical anxiety disorders or anxiety symptoms among adult patients with psoriasis and characterize the effect of anti-psoriatic interventions on clinical anxiety disorders or anxiety symptoms. We searched PubMed, EMBASE, and the Cochrane Database using search terms 'psoriasis' and 'anxiety'. Results were tabulated and verified by two independent reviewers. Meta-analyses were not performed due to heterogeneity of data. Of 213 publications identified, 938 194 patients from 15 papers were included. The mean age ranged from 31.9-59.4 years old, with a mean PASI score of 7.65-22.8 (reported by nine studies) and a body surface area involvement of 25.9-39.8% (reported by two studies). The prevalence of anxiety in patients with psoriasis was 7-48%, which was significantly higher than healthy controls in two of three studies (HR 1.29-1.31, P = 0.001 and OR 2.91 [95% CI, 2.01-4.21], P < 0.001). Four of five studies (n = 2029) demonstrated an improvement in anxiety symptoms with psoriasis treatment. This review demonstrates a high prevalence of anxiety of adult patients with psoriasis suggesting that patients would benefit from systematic screening. Although the data suggest that anxiety may be improved through various psoriasis treatments, larger prospective randomized trials are needed to confirm this effect.

Down-regulation of microRNA-143 is associated with colorectal cancer progression.

OBJECTIVE: Colorectal cancer (CRC) is one of the most prevalent carcinomas worldwide. Tumor metastasis and recurrence are leading causes of CRC-related deaths. Given the role of microRNA (miRNA) in CRC invasion and metastasis, we explored the association between miRNA-143 expression and clinicopathologic characteristics in CRC, as well as the effects of miRNA-143 on CRC cell invasion in vitro. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to assess the expression of miR-143 in tissue specimens and cell lines. CCK-8 test and transwell assay were conducted to explore the effects of miR-143 on the proliferation and invasion of CRC cell lines, respectively. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-143 and epidermal growth factor receptor 3 (ERBB3) in CRC. RESULTS: miR-143 was down-regulated in human CRC tissues, its expression negatively correlated with CRC metastasis. miR-143 negatively regulated ERBB3 expression by directly targeting its 3'UTR in human colorectal cancer cells. Overexpression of miR-143 inhibited CRC cells invasion but did not affect its proliferation in vitro. Knockdown of ERBB3 also significantly suppressed CRC cells invasion. CONCLUSIONS: These data suggest that miR-143 suppressed the invasion and metastasis ability by suppressing ERBB3 expression in CRC cells, providing a novel and promising therapeutic target for the prevention and treatment of CRC.

BCOR regulates myeloid cell proliferation and differentiation.

BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1). Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukemia (AML). However, the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with upregulated expression of Hox genes. Mutation of Bcor reduced protein levels of RING1B, an H2A ubiquitin ligase subunit of PRC1 family complexes and reduced H2AK119ub upstream of upregulated HoxA genes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with enhanced cell proliferation and myeloid differentiation. Our results strongly suggest that BCOR plays an indispensable role in hematopoiesis by inhibiting myeloid cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes.

Diabetes self-management programmes in older adults: a systematic review and meta-analysis.

AIM: The evidence for self-management programmes in older adults varies in methodological approaches, and disease criteria. Using predetermined methodological criteria, we evaluated the effect of diabetes-specific self-management programme interventions in older adults. METHODS: The EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from January 1980 to November 2013, as were reference lists from systematic reviews, meta-analyses and clinical practice guidelines. A total of 13 trials met the selection criteria, which included 4517 older adult participants; 2361 participants randomized to a diabetes self-management programme and 2156 to usual care. RESULTS: The pooled effect on HbA(1c) was a reduction of -2 mmol/mol (-0.2%; 95% CI -0.3 to -0.1); tailored interventions [-3 mmol/mol (-0.2%; 95% CI -0.4 to -0.1)] or programmes with a psychological emphasis [-3 mmol/mol (-0.2; 95% CI -0.4 to -0.1)] were most effective. A pooled treatment effect on total cholesterol was a 5.81 mg/dl reduction (95% CI -10.33 to -1.29) and non-significant reductions in systolic and diastolic blood pressure. CONCLUSIONS: Diabetes self-management programmes for older adults demonstrate a small reduction in HbA(1c), lipids and blood pressure. These findings may be of greater clinical relevance when offered in conjunction with other therapies.

[Protective effects of gangliosides on cerebral neuronal damage of rat during acute hypoxia].

OBJECTIVE: To observe the preventive and therapeutic effects of gangliosides on acute altitude hypoxic brain damage. METHOD: Fifteen Wistar rats, weighed 180-220 g, were randomly divided into 3 groups, hypoxia group A, hypoxia group B and normoxia group. The rats in hypoxia group A were exposed to a simulated altitude of 7000 m for 5 hours and the rats in hypoxia group B were exposed to hypoxia after intraperitoneal administration of mixed gangliosides (100 mg/kg/d) for 3 days. RESULT: Gangliosides could ameliorate the severity of damage in neuronal bodies, cellular skeletons and synapses, especially in synapses. CONCLUSION: It is suggested that gangliosides are effective in preventing and treating hypoxic brain damages by decreasing the accumulation of intracellular Ca2+, and stabilizing CaM and CaM PKII activity during acute hypoxia.

[Urogenital rhabdomyosarcoma in children: analysis of 39 cases].

From 1967 to 1992, 39 patients with urogenital rhabdomyosarcoma were admitted to our hospital. Of them 30 were male and 8 female and their age ranged from 4 months to 14 years (32 were less than 5 years). Primary tumor was located in bladder or/and prostate in 26, paratesticule 9, vagina 3, and penis 1. Among the 31 patients receiving treatment, 23 were followed up. There were 15 (65%) survivors, including 13 who were free from tumor for over 4 years. The eldest two patients were 20 and 21 years of age. Two patients with vaginal tumor and 4 with bladder tumor preserved their organs with normal function. Biopsy were done only in 8 patients. In recent years, conservative surgery combined with chemotherapy for urogenital rhabdomyosarcoma has been justified.

[Exocrine function of the pancreas and pathological histology of the stomach in patients with stomach yin deficiency syndrome (SYDS) research on SYDS following abdominal operation or with severe acute abdominal diseases (Part 3)].

Exocrine function of pancreas (BT-PABA test) in 13 patients with SYDS was examined and gastric membrane in 5 cases with SYDS other than gastric diseases was observed under light- and electro-microscopy. The results were as follows: urine rate of recovery of PABA in SYDS was 35. 42 +/- 14.33% and that in the control with same age was 64.70 +/- 10.55%. The rate in SYDS was decreased obviously (P less than 0.001). Under light microscopy gastric mucosa of patients with SYDS showed slight gland degenerative atrophy, smaller cytoplasm, eosinophilic decrease of parietal cells and infiltration of inflammatory cells in interstitial tissue. Under electro-microscopy, the main changes of the gastric mucosa with SYDS were severe mitochondria damage, inflating rough endoplasmic pools and large vacuole at which membrane major particles of ribosomes disappeared, degenerated secretory vessels and formation of myelin figure in parietal cells, decrease of secretory particles in main cells, degeneration in some degree and decrease of nervous secretory particles in G cells and damaged interstitial capillaries. The results in this study suggested that the exocrine function of pancreas in patients with SYDS after abdominal operation or with severe acute abdominal diseases was decreased and there were some damages in energy supply and protein manufacturing systems of the gastric mucosa and functional disturbances of main cells, parietal cells and G cells in patients with SYDS.

Congenital anterior urethral valves and diverticula--analysis of 50 cases.

Fifty patients with anterior urethral valvular obstruction were reviewed. All of them had difficulty in urination, 15 patients had recurrent high fever, 8 patients had features of renal failure, and 5 patients had a reducible swelling at the penoscrotal junction. With voiding cystourethrograph, distension of the proximal urethra was seen in all patients. Diverticula of the urethra could be demonstrated in 15 patients. Eight patients had unilateral, and 2 patients had bilateral vesicoureteral reflux. With intravenous pyelograph, unilateral hydronephrosis was seen in 4 and bilateral hydronephrosis was seen in 19. Excision of the valve and/or diverticulum with primary repair was performed in 29 patients, 28 were cured, 1 died of renal failure 8 years postoperatively. Multi-stage procedures were performed in 7 patients. Transurethral fulguration of the valve was performed in 14 patients. Nine patients were cured, secondary operations were needed in 5 patients.