[Expression changes of RNA m6A regulators in mouse cerebellum affected by hypobaric hypoxia stimulation].

Objective: To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment. Methods: Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella. Results: Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced (P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella (P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice (P<0.05). Conclusions: Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

[Diaphragmatic dysfunction post-COVID-19 infection: report of two cases].

Following the global outbreak of COVID-19, many patients have suffered from multi-system complications and long-term sequelae caused by the virus. Diaphragm dysfunction is an obscure post-COVID-19 symptom. Although a few cases of diaphragm dysfunction caused by COVID-19 infection have been reported abroad, there are no relevant reports in China. Herein, we present two cases of patients with respiratory distress after COVID-19 infection. On admission, dynamic chest radiographs revealed diaphragm dysfunction in these patients. Further investigations including diaphragm ultrasound, neurophysiological examinations, transdiaphragmatic pressure measurements cranial MRI, and antibody testing for autoimmune diseases, were conducted. The final diagnoses were severe myasthenia gravis induced by COVID-19 infection and diaphragmatic nerve and muscle involvement caused by COVID-19 infection. Both patients showed improvement in symptoms after treatment. Therefore, we summarized our case, with a review of the relevant literature to improve the understanding of the disease and to provide clinical evidence for future diagnosis and treatment.

Evaluation of QSAR models for predicting mutagenicity: outcome of the Second Ames/QSAR international challenge project.

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.

[Effects of RNA M6A demethylase ALKBH5 gene deficiency on morphology and function of cerebellum in aged mice].

Objective: To investigate the effects of RNA m6A demethylase ALKBH5 gene deficiency on cerebellar morphology and function in the aged mice, and to explore the role of ALKBH5 in cerebellar degeneration. Methods: Western blot was performed to detect the protein level of ALKBH5 in the cerebellum of wild-type mice of various ages. The expression of NeuN, Calbindin-D28K, MAP2, GFAP and other proteins in the cerebella of middle-aged (12-month-old) and aged (18-month-old) wild-type mice and ALKBH5-/- mice was examined using immunohistochemistry. The balance beam test and gait analysis were performed to test the balance ability and motor coordination of the mice. Results: With aging of the mice, the expression of ALKBH5 in the cerebellum increased gradually in an age-dependent manner. In the aged mice, but not middle-aged mice, the body weight, whole brain weight and cerebellum weight of ALKBH5-/- mice decreased by 15%, 10% and 21%, respectively (P<0.05). The expression of ALKBH5 in the Purkinje cells was much higher than that in other types of neural cells. Correspondingly, ALKBH5-deficiency caused 40% reduction in the number of Purkinje cells, as well as the length and density of neuronal dendrites in the aged mice (P<0.01). In addition, the time for the aged ALKBH5-/- mice to pass the balance beam was 70% longer than that of the wild type mice of the same age, with unstable gaits (P<0.01). Conclusions: Gene deficiency of RNA m6A demethylase ALKBH5 causes cerebellar atrophy, Purkinje neuron loss and damage in the aged mice. These changes eventually affect mice's motor coordination and balance ability. These results suggest that imbalanced RNA m6A methylation may lead to neurodegenerative lesions in the cerebellum of mice.

Robotic versus laparoscopic left colectomy with complete mesocolic excision for left-sided colon cancer: a multicentre study with propensity score matching analysis.

BACKGROUND: Robotic surgery for right-sided colon and rectal cancer has rapidly increased; however, there is limited evidence in the literature of advantages of robotic left colectomy (RLC) for left-sided colon cancer. The purpose of this study was to compare the outcomes of RLC versus laparoscopic left colectomy (LLC) with complete mesocolic excision (CME) for left-sided colon cancer. METHODS: Patients who had RLC or LLC with CME for left-sided colon cancer at 5 hospitals in China between January 2014 and April 2022 were included. A one-to-one propensity score matched analysis was performed to decrease confounding. The primary outcome was postoperative complications occurring within 30 days of surgery. Secondary outcomes were disease-free survival, overall survival and the number of harvested lymph nodes. RESULTS: A total of 292 patients (187 males; median age 61.0 [20.0-85.0] years) were eligible for this study, and propensity score matching yielded 102 patients in each group. The clinical-pathological characteristics were well-matched between groups. The two groups did not differ in estimated blood loss, conversion to open rate, time to first flatus, reoperation rate, or postoperative length of hospital stay (p > 0.05). RLC was associated with a longer operation time (192.9 ± 53.2 vs. 168.9 ± 52.8 minutes, p=0.001). The incidence of postoperative complications did not differ between the RLC and LLC groups (18.6% vs. 17.6%, p = 0.856). The total number of lymph nodes harvested in the RLC group was higher than that in the LLC group (15.7 ± 8.3 vs. 12.1 ± 5.9, p< 0.001). There were no significant differences in 3-year and 5-year overall survival or 3-year and 5-year disease-free survival. CONCLUSIONS: Compared to laparoscopic surgery, RLC with CME for left-sided colon cancer was found to be associated with higher numbers of lymph nodes harvested and similar postoperative complications and long-term survival outcomes.

Iron Regulatory Protein 1 is Required for the Propagation of Inflammation in Inflammatory Bowel Disease.

Objective: Inflammatory bowel diseases (IBD) are complex disorders. Iron accumulates in the inflamed tissue of IBD patients, yet neither a mechanism for the accumulation nor its implication on the course of inflammation are known. We hypothesized that the inflammation modifies iron homeostasis, affects tissue iron distribution and that this in turn perpetuates the inflammation. Design: This study analyzed human biopsies, animal models and cellular systems to decipher the role of iron homeostasis in IBD. Results: We found inflammation-mediated modifications of iron distribution, and iron-decoupled activation of the iron regulatory protein (IRP)1. To understand the role of IRP1 in the course of this inflammation-associated iron pattern, a novel cellular co-culture model was established, that replicated the iron-pattern observed in vivo, and supported involvement of nitric oxide in the activation of IRP1 and the typical iron pattern in inflammation. Importantly, deletion of IRP1 from an IBD mouse model completely abolished both, the misdistribution of iron and intestinal inflammation. Conclusion: These findings suggest that IRP1 plays a central role in the coordination of the inflammatory response in the intestinal mucosa and that it is a viable candidate for therapeutic intervention in IBD.

[Predictive models and prophylactic strategies for anastomotic leakage in colorectal surgery].

Anastomotic leakage (AL) has always been a persistent issue for colorectal surgeons. It is still difficult to reduce the incidence of AL despite the advances in technology and equipment. With the development of evidence-based medicine, increasing high-risk factors for AL have been identified. How to efficiently and systematically combine and quantify these isolated risk factors to provide a scientific early warning of AL in clinical practices and help surgeons in choosing the optimal prophylactic strategies, is of great significance for reducing the incidence of AL. There are generally two types of AL prediction models in colorectal surgery, including prognostic models (for preoperative and intraoperative AL prediction) and diagnostic models (for early warning and improving the early diagnosis rate of AL). Prophylactic strategies for AL include stabilizing the underlying diseases, improving anemia and hypoalbuminemia, choosing an appropriate operative time window, and emphasizing and improving anastomotic techniques (including choosing an appropriate size of stapler). However, a prophylactic ostomy is still the most common method for surgeons. However, how to reduce the morbidity of complications following prophylactic ostomy and how to avoid the conversion of the prophylactic stoma to permanent stoma need further study.

Role of transanal drainage tubes in preventing anastomotic leakage after low anterior resection: a meta-analysis of randomized controlled trials.

BACKGROUND: The transanal drainage tube (TDT) is thought to reduce the incidence of anastomotic leakage (AL) in patients with low anterior resection (LAR). However, results from different clinical trials are inconsistent, although nearly all meta-analyses agree on the efficacy. In contrast to results of many previous studies, 2 recent independent randomized controlled trials (RCTs) suggest that the use of TDT does not prevent AL. We performed a meta-analysis including only RCTs to compare patients with TDTs vs. those without TDTs in terms of AL rate. METHODS: A systematic literature search was performed in the PubMed, Embase, Cochrane Library databases, Clinicaltrials.gov and WHO/ICTRP from inception until February 14, 2022. RCTs that evaluated the role of TDTs in AL prevention in patients who underwent LAR for rectal cancer were included. A meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by two authors independently, and random-effects models were implemented. The main outcome was AL, and the secondary outcome was the grade of AL. RESULTS: Three RCTs were included involving a total of 1115 participants (559 patients in the TDT group and 556 in the non-TDT group). No significant difference in the AL rate was detected (RR = 0.69, 95% confidence interval (CI) 0.42-1.15, p = 0.15, I2 = 21%, very low certainty evidence). The incidence of grade C AL was possibly lower in the TDT group (RR = 0.33, 95% CI 0.11-1.01, p = 0.05, very low certainty evidence), while the rate of grade B AL was similar between the two groups (RR = 1.17, 95% CI 0.66-2.08, p = 0.59, very low certainty evidence). CONCLUSIONS: The present meta-analysis suggests that TDTs are not effective in reducing the overall incidence of AL, but possibly have a potential benefit in reducing the occurrence of grade C AL in patients with LAR. Based on the current limited data and existing heterogeneity, the inclusion of larger populations and the identification of more uniform indications for TDT need to be addressed in future studies.

[Efficacy and safety of combination therapy with chemotherapy, programmed death-1 inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma].

Objective: To investigate the efficacy and safety of the combination therapy with chemotherapy, programmed death-1 (PD-1) inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma (DDLPS). Methods: The clinical data of patients with dedifferentiated liposarcoma who received chemotherapy combined with PD-1 inhibitor and anlotinib in the Department of Medical Oncology, Zhongshan Hospital Affiliated to Fudan University from January 1, 2020 to November 30, 2021 were retrospectively analyzed. A total of 24 patients were included in this study, including 12 males and 12 females, with a median age of onset of 56 years (range, 31-69 years). Efficacy and safety in those patients were assessed. Results: All patients had unresectable or metastatic dedifferentiated liposarcoma with G2 (moderate differentiation) or G3 (differential differentiation) in a concise three-grade grading scheme of tumor pathology. Twelve patients received the regimen as the first-line treatment, while the other 7 taken the regimen as second-line treatment and 5 as third-line or above. The median follow-up time for overall survival (OS) was 7.7 months. The overall response rate (ORR) was 20.8% (5/24) and disease control rate (DCR) was 83.3% (20/24) with 5 partial response (PR), 15 stable disease (SD) and 4 progressive disease (PD). Overall, the median progression-free survival (PFS) was 4.9 months (95%CI: 3.4-16.2 months). The ORR of anthracycline-based, eribulin-based or gemcitabine-based regimens was 1/12, 2/6 and 2/6, respectively; and the median PFS was 7.7, 7.3 and 4.4 months, respectively. Waterfall plots showed notable tumor shrinkage of any degree in eribulin and gemcitabine-based regimens(3/6 and 2/6, respectively), while there were more patients presented with SD in anthracycline-based group(9/12). Common adverse reactions included myelosuppression, fatigue, anorexia, rash, pruritus, palpitate, hypothyroidism and hypertension. Conclusions: The combination regimen with chemotherapy, PD-1 inhibitor and anlotinib in the treatment of advanced DDLPS is effective and well tolerable. There are more responders in eribulin or gemcitabine-based regimens.

Exploring the role of antibiotics and steroids in managing respiratory diseases.

Respiratory diseases (RDs), such as chronic obstructive pulmonary disease, cystic fibrosis, asthma, and pneumonia, are associated with significant morbidity and mortality. Treatment usually consists of antibiotics and steroids. Relevant published literature reviews, studies, and clinical trials were accessed from institutional and electronic databases. The keywords used were respiratory diseases, steroids, antibiotics, and combination of steroids and antibiotics. Selected articles and literature were carefully reviewed. Antibiotics are often prescribed as the standard therapy to manage RDs. Types of causative respiratory pathogens, spectrum of antibiotics activity, route of administration, and course of therapy determine the type of antibiotics that are prescribed. Despite being associated with good clinical outcome, treatment failure and recurrence rate are still high. In addition, antibiotic resistance has been widely reported due to bacterial mutations in response to the use of antibiotics, which render them ineffective. Nevertheless, there has been a growing demand for corticosteroids (CS) and antibiotics to treat a wide variety of diseases, including various airway diseases, due to their immunosuppressive and anti-inflammatory properties. The use of CS is well established and there are different formulations based on the diseases, such as topical administration, tablets, intravenous injections, and inhaled preparations. Both antibiotics and CS possess similar properties in terms of their anti-inflammatory effects, especially regulating cytokine release. Thus, the current review examines and discusses the different applications of antibiotics, CS, and their combination in managing various RDs. Drawbacks of these interventions are also discussed.

Effect of decoction of Fuzheng Jiedu Xiaoji formula plus chemoembolization on primary liver cancer in patients.

OBJECTIVE: To investigate the effect of the decoction of Fuzheng Jiedu Xiaoji formula (, FJXF) plus chemoembolization (TACE) on primary liver cancer (PLC) in patients, and study the underlying mechanism. METHODS: Patients with PLC who met the inclusion criteria were randomized into case group and control group. The case group was treated with FJXF combined with TACE. The control group was treated with TACE alone. The short-term clinical effect was evaluated; liver biochemistry, liver function index and multidrug resistance-associated indicators were detected. RESULTS: FJXF combined with TACE in the case group significantly increased the disease control rate than TACE alone in the control group (83.3% 61.1%). There was a reduction in the serum alpha-fetoprotein at 8 weeks after treatment in each group, while no difference between the two groups. The same trend can be observed for transaminase and direct bilirubin in both groups. In the case group, it showed a significant increase for albumin at 8 weeks after treatment, while no change in the control group. Multidrug resistance-associated indicators for multidrug resistance protein 1 and p-glycoprotein were upregulated in the case group but remained stable in the control group. CONCLUSIONS: FJXF combined TACE had a better short-term effect than TACE alone in patients with PLC. The potential mechanism was probably associated with alleviated multidrug resistance induced by FJXF. Additionally, FJXF didn't increase the risk of liver damage in the combined therapy.

Angular dependence of spin-flop transition in triangular lattice antiferromagnet Cu2(OH)3Br.

We report angular dependence of spin-flop transition in triangular lattice antiferromagnet Cu2(OH)3Br by angle-dependent magnetization and ESR measurements. The results show that the antiferromagnetic easy magnetization axis is the diagonal direction (θ= 45°) of theac*plane, i.e., the orientation of Cu1 spins based on the magnetic structure (2020Phys. Rev. Lett.125037204), whereas the spin-flop axis is thebaxis. A phenomenological model is proposed to describe the angle-dependent spin-flop transitions. Based on this model, Cu1 spins are sensitive to external magnetic field, while Cu2 spins are robust against to the field, showing partial decoupling. The model is expected to be used in other uniaxial antiferromagnets with a more general easy axis and complex spin-flop transitions.

Combined transabdominal-transanal surgical approach for iatrogenic rectovaginal fistula: two case reports.

Rectovaginal fistula (RVF) is a type of anastomotic leakage that may occur after low anterior resection for rectal cancer. The repair of RVF can be challenging because of the scar tissue stenosis and incomplete obstruction. Two patients presented in our department with vaginal faecal discharge almost 7 months after the radical resection of rectal cancer. On vaginal examination, titanium nails related to the rectal surgery were found in the vaginal wall. The patients were diagnosed with RVF. Considering that RVF positions in the patients were high and might adhere to the pelvic tissue, a combined transabdominal-transanal resection and vaginal repair surgery was performed. About 3 months after surgery, both patients underwent colonic closure surgery, with consequent good recovery. A combined transabdominal-transanal approach may provide distinct advantages in surgical repair of difficult cases of RVF.

Combined transabdominal-transanal surgical approach for iatrogenic rectovaginal fistula: two case reports.

Rectovaginal fistula (RVF) is a type of anastomotic leakage that may occur after low anterior resection for rectal cancer. The repair of RVF can be challenging because of the scar tissue stenosis and incomplete obstruction. Two patients presented in our department with vaginal faecal discharge almost 7 months after the radical resection of rectal cancer. On vaginal examination, titanium nails related to the rectal surgery were found in the vaginal wall. The patients were diagnosed with RVF. Considering that RVF positions in the patients were high and might adhere to the pelvic tissue, a combined transabdominal-transanal resection and vaginal repair surgery was performed. About 3 months after surgery, both patients underwent colonic closure surgery, with consequent good recovery. A combined transabdominal-transanal approach may provide distinct advantages in surgical repair of difficult cases of RVF.

Effectiveness of a childbirth massage programme for labour pain relief in nulliparous pregnant women at term: a randomised controlled trial.

INTRODUCTION: The effect of massage for pain relief during labour has been controversial. This study investigated the efficacy of a programme combining intrapartum massage, controlled breathing, and visualisation for non-pharmacological pain relief during labour. METHODS: This randomised controlled trial was conducted in two public hospitals in Hong Kong. Participants were healthy low-risk nulliparous Chinese women ≥18 years old whose partners were available to learn massage technique. Recruitment was performed at 32 to 36 weeks of gestation; women were randomised to attend a 2-hour childbirth massage class at 36 weeks of gestation or to receive usual care. The primary outcome variable was the intrapartum use of epidural analgesia or intramuscular pethidine injection. RESULTS: In total, 233 and 246 women were randomised to the massage and control groups, respectively. The use of epidural analgesia or pethidine did not differ between the massage and control groups (12.0% vs 15.9%; P=0.226). Linear-by-linear analysis demonstrated a trend whereby fewer women used strong pharmacological pain relief in the massage group, and a greater proportion of women had analgesic-free labour (29.2% vs 21.5%; P=0.041). Cervical dilatation at the time of pethidine/epidural analgesia request was significantly greater in the massage group (3.8 ± 1.7 cm vs 2.3 ± 1.0 cm; P<0.001). CONCLUSION: The use of a massage programme appeared to modulate pain perception in labouring women, such that fewer women requested epidural analgesia and a shift was observed towards the use of weaker pain relief modalities; in particular, more women in the massage group were analgesic-free during labour.

[Preliminary application and efficacy analysis of transumbilical single-incision plus one port robotic total mesorectal excision].

Objective: To investigate the feasibility of transumbilical single-incision plus one port (SIPOP) robotic total mesorectal excision. Methods: Clinical data of a 70-year-old male patient with BMI 22.1 kg/m(2) who successfully underwent transumbilical single-incision plus 1 port robotic total mesorectal resection of upper rectal cancer at the General Surgery Department of Daping Hospital of Army Military Medical University on September 18, 2019 were retrospectively analyzed. Preoperative colonoscopy revealed that the distance of upper rectal cancer to anal edge was 14 cm, and the tumor size was 2.5 cm×1.5 cm×1 cm. Pathological result confirmed rectal moderately differentiated adenocarcinoma. The preoperative abdominal CT showed thickened bowel-wall of upper rectum and the blurred perirectal fat, suggesting tumor infiltration. Results: The operation was successful. There were no conversion to laparotomy or abdominal auxiliary incision, and the mesorectum of the specimen was intact. The operation time was 165 minutes, the blood loss was about 20 ml, and there were no complications such as injury to peripheral organs. Postoperative pathology showed ulcerative moderately differentiated adenocarcinoma of the upper rectum with TNM stage IVA (T4N2b). The postoperative recovery was smooth. Patient ambulated on the 1st day, the catheter was removed on the 7th day, and discharged from the hospital on the 8th day. Conclusion: The transumbilical SIPOP robotic total mesorectal excision is safe, effective and feasible.