Combined repetitive transcranial magnetic stimulation and gut microbiota modulation through the gut-brain axis for prevention and treatment of autism spectrum disorder.

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions characterized by enduring impairments in social communication and interaction together with restricted repetitive behaviors, interests, and activities. No targeted pharmacological or physical interventions are currently available for ASD. However, emerging evidence has indicated a potential association between the development of ASD and dysregulation of the gut-brain axis. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive diagnostic and therapeutic approach, has demonstrated positive outcomes in diverse psychiatric disorders; however, its efficacy in treating ASD and its accompanying gastrointestinal effects, particularly the effects on the gut-brain axis, remain unclear. Hence, this review aimed to thoroughly examine the existing research on the application of rTMS in the treatment of ASD. Additionally, the review explored the interplay between rTMS and the gut microbiota in children with ASD, focusing on the gut-brain axis. Furthermore, the review delved into the integration of rTMS and gut microbiota modulation as a targeted approach for ASD treatment based on recent literature. This review emphasizes the potential synergistic effects of rTMS and gut microbiota interventions, describes the underlying mechanisms, and proposes a potential therapeutic strategy for specific subsets of individuals with ASD.

A Systematic Review and Meta-analysis of Renin-angiotensin System Inhibitors and Angiotensin Receptor Neprilysin Inhibitors in Preventing Recurrence After Atrial Fibrillation Ablation.

ABSTRACT: To systematically evaluate the efficacy and safety of renin-angiotensin system inhibitors (RASIs) and angiotensin receptor neprilysin inhibitors in preventing the recurrence of atrial fibrillation after atrial fibrillation ablation, we have written this meta-analysis. We systematically searched randomized controlled trials or cohort studies on RASIs and angiotensin receptor neprilysin inhibitor-sacubitril/valsartan (SV) in preventing the recurrence of atrial fibrillation. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Afterward, the meta-analysis was performed using RevMan 5.3 software. This meta-analysis results showed that the recurrence rate of atrial fibrillation after ablation in subjects using RASIs was lower than that in subjects not using them [relative risk = 0.85, 95% confidence interval (CI) (0.72-0.99), P = 0.03]; the recurrence rate in subjects using SV was lower than that in subjects using RASIs [RR= 0.50, 95% CI (0.37-0.68), P < 0.00001]. These results show that both the use of RASIs and SV can prevent the recurrence of after atrial fibrillation ablation, among which the use of SV is more effective.

Balancing equity and policyholder protection: Assessing insurer's interests in green lending under cap-and-trade regulations.

This paper presents a contingent claim model designed to assess an insurer's equity within the framework of carbon trading regulations imposed on borrowing firms while also considering the integration of green lending. The development of this model is particularly relevant for regions with established carbon trading markets, with a specific focus on the post-period following the 2015 Paris Agreement concerning climate change. We focus on shareholders and policyholders to optimize equity and ensure maximum protection. Strict caps in cap-and-trade harm interest margins, reducing guaranteed rates for equity maximization and compromising policyholder protection. Government intervention through sustainable production carbon trading hinders win-win outcomes. Green subsidies can improve insurer margins, but achieving win-win solutions remains challenging. A collective approach is needed to share sustainable production and finance benefits among diverse economic sectors.

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis

ABSTRACT Purpose: To compare the effectiveness and safety of marketed oral drugs for overactive bladder based on a systematic review and network meta-analysis approach. Methods: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. Result: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Conclusion: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Rapid health technology assessment of the novel endonuclease inhibitor baloxavir for the treatment of influenza.

Through a Rapid Health Technology Assessment (RHTA), we evaluated the efficacy, safety and cost-effectiveness of baloxavir in the treatment of influenza, providing the necessary scientific information and evidence-based basis for healthcare professionals and health insurance decision-makers in making rational selections. Through systematic searches of Pubmed, Embase, Web of Science, The Cochrane Register of Clinical Trials database and the official website of Health Technology Assessment (HTA) agencies, we collected systematic reviews (SR)/Meta-analysis, cost-effectiveness evaluations and HTA reports of baloxavir for influenza, with a search time frame of date of database establishment to July 31, 2022. We then performed data extraction, literature screening and quality evaluation on the literature that met our selection criteria, after which the results of the studies were pooled and qualitatively described for analysis. 10 studies were included, including 6 SR/Meta-analysis, three economics studies, and 1 HTA report. In terms of efficacy, baloxavir had an advantage over oseltamivir for all three types of influenza patients (otherwise healthy patients, high-risk patients, and patients are not separated into groups with and without underlying health conditions) concerning change in virus titer from baseline at 24 and 48 h; about otherwise healthy patients and high-risk patients, baloxavir had an advantage over peramivir; pertaining to high-risk patients, baloxavir had an advantage over laninamivir; the above differences between groups were all statistically significant. In terms of safety, in otherwise healthy patients and patients are not separated into groups with and without underlying health conditions, baloxavir significantly reduced the incidence of DRAEs and nausea compared with oseltamivir, as well as significantly reduced the incidence of DRAEs compared with laninamivir; in patients are not separated into groups with and without underlying health conditions, baloxavir significantly reduced the incidence of AEs and diarrhoea compared with oseltamivir; the differences between the above groups were all statistically significant. Economically, in Japanese adult influenza patients and high-risk populations, the Quality-Adjusted Life Years (QALY) of baloxavir slightly triumphed over that of laninamivir (Δ = 0.000112 and 0.00209 QALY per 1 patient, respectively); moreover, the incremental cost-effectiveness ratio (ICER: 2,231,260 and 68,855 yen/QALY, respectively) was below the willingness-to-pay (WTP) threshold (5,000,000 yen/QALY); in Chinese adult influenza patients without underlying diseases and adult high-risk influenza patients, baloxavir had a higher QALY compared with oseltamivir (Δ = 0.000246 and 0.000186 respectively), however, their ICER (12,230 and 64,956 RMB/QALY) was above the local WTP threshold (10,000 RMB/QALY) and thus did not provide a cost-effectiveness advantage. Baloxavir had a favorable efficacy and safety profile compared to neuraminidase inhibitors (NAIs), and the currently available evidence suggested that it had an economic advantage only in Japan.

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis.

bladder based on a systematic review and network meta-analysis approach. METHODS: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. RESULT: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. CONCLUSION: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

If we should remove internal fixation devices for rib fractures?

BACKGROUND: Internal fixation for rib fractures has been widely carried out worldwide, and its surgical efficacy has been recognized. However, there is still controversy about whether implant materials need to be removed. At present, the research on this topic is still lacking at home and abroad. Therefore, in this study, the patients undergoing removal of internal fixation for rib fractures in our department within one year were followed up, to statistically analyze implant-related complications, postoperative complications and postoperative remission rate. METHODS: A retrospective analysis was conducted on 143 patients undergoing removal of internal fixation for rib fractures from 2020 to 2021 in our center. The implant-related complications, postoperative complications and postoperative remission rate of patients with internal fixation were analyzed. RESULTS: In this study, a total of 143 patients underwent removal of internal fixation, among which 73 suffered from preoperative implant-related complications (foreign-body sensation, pain, wound numbness, sense of tightness, screw slippage, chest tightness, implant rejection), and 70 had no post operative discomfort but asked for removal of internal fixation. The average interval between rib fixation and removal was 17 ± 9.00 (months), and the average number of removed materials was 5.29 ± 2.42. Postoperative complications included wound infection (n = 1) and pulmonary embolism (n = 1). of the 73 patients with preoperative implant-related complications, the mean postoperative remission rate was 82%. Among the 70 patients without preoperative discomfort, the proportion of discomforts after removal was 10%. No perioperative death occurred. CONCLUSION: For patients with internal fixation for rib fractures, removal of internal fixation can be considered in the case of implant-related complications after surgery. The corresponding symptoms can be relieved after removal. The removal presents low complication rate, and high safety and reliability. For patients without obvious symptoms, it is safe to retain the internal fixation in the body. For the asymptomatic patients who ask for removal of internal fixation, the possible risk of complications should be fully informed before removal.

Efficacy and safety of novel biologics in the treatment of lupus nephritis based on registered clinical trials: a systematic review and network meta-analysis.

To compare the clinical effectiveness and safety of novel biologics for the treatment of lupus nephritis based on a reticulated meta-analysis approach. Registered clinical trials in 4 major databases (PubMed, Embase, Web of Science, The Cochrane Register of Clinical Trials) and ClinicalTrials.gov were systematically searched with a search time frame of build to June 2022. And we screened registered randomized controlled clinical trials of biologics for the treatment of lupus nephritis according to the protocol's nadir criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 and Review Manager 5.3 software to compare and rank differences in effectiveness and safety between the biologics. A total of 10 registered randomized controlled clinical trials involving 2148 subjects were included in this study. The interventions were ranked from best to worst in terms of the primary outcome indicator of effectiveness, renal complete remission: belimumab > anifrolumab (900 + 300) mg > obinutuzumab > ocrelizumab 400 mg > abatacept 30/10 mg/kg > belimumab + rituximab > abatacept 10/10 mg/kg > abatacept (30/10 + 10/10) mg/kg > placeo > ocrelizumab 1000 mg > rituximab > anifrolumab 300 mg, belimumab was superior to placebo [OR = 1.75, 95% CI (1.13, 2.70)] and anifrolumab 300 mg [OR = 3.27, 95% CI (1.05, 10.14)], anifrolumab (900 + 300) mg was superior to anifrolumab 300 mg [OR = 3.56, 95% CI (1.30, 9.76)], and all were statistically significant. The ranking of each intervention in terms of overall renal remission for secondary outcome indicators from best to worst was: obinutuzumab > belimumab + rituximab > anifrolumab (900 + 300) mg > ocrelizumab 1000 mg > ocrelizumab 400 mg > belimumab > rituximab 1000 mg > abatacept 30/10 mg/kg > abatacept (30/10 + 10/10) mg/kg > placeo > abatacept 10/10 mg/kg > anifrolumab 300 mg, obinutuzumab was superior to placebo [OR = 2.27, 95% CI (1.11, 4.67)] and belimumab was also superior to placebo [OR = 1.56, 95% CI (1.07, 2.27)], and all were statistically significant. In terms of safety, with a focus on serious adverse events and serious infections, the results were: Serious adverse events at 1 year of monitoring occurred better with ocrelizumab 1000 mg than ocrelizumab 400 mg [OR = 0.51, 95% CI (0.29, 0.89)] and were statistically different; serious adverse events at 2 years of monitoring infection adverse events occurred better with obinutuzumab than with abatacept (30/10 + 10/10) mg/kg [OR = 0.24, 95% CI (0.07, 0.81)] and were statistically different. The safety of the new biologics in combination with conventional standard therapies is generally good, but it is belimumab and obinutuzumab that are most effective in achieving complete and overall remission in the kidney. This study protocol has been registered with PROSPERO, with a registration number of CRD42021262498.

Mouse nerve growth factor suppresses neuronal apoptosis in valproic acid-induced autism spectrum disorder rats by regulating the phosphoinositide-3-kinase/serine/threonine kinase signaling pathway.

BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social communication and restrictive behaviors. Mouse nerve growth factor (mNGF), a neurotrophic factor, is critical for neuronal growth and survival, and the mNGF treatment is considered a promising therapy for neurodegeneration. In light of this, we aimed to evaluate the effect of mNGF on neurological function in ASD. METHODS: An ASD rat model was established by intraperitoneal injection of valproic acid (VPA). Social behavior, learning, and memory of the rats were measured. TdT-mediated dUTP Nick-end labeling and Nissl assays were performed to detect neuronal apoptosis and survival in the hippocampus and prefrontal cortex. Apoptosis-related proteins and oxidative stress markers were detected. RESULTS: mNGF improved locomotor activity, exploratory behavior, social interaction, and spatial learning and memory in VPA-induced ASD rats. In the hippocampus and prefrontal cortex, mNGF suppressed neuronal apoptosis, increased the number of neurons, superoxide dismutase, and glutathione levels, and decreased reactive oxygen species, nitric oxide, TNF-α, and IL-1ß levels compared with the VPA group. In addition, mNGF increased the levels of Bcl-2, p-phosphoinositide-3-kinase (PI3K), and p-serine/threonine kinase (Akt), and decreased the levels of Bax and cleaved caspase-3, while the PI3K inhibitor LY294002 reversed these effects. CONCLUSION: These data suggest that mNGF suppressed neuronal apoptosis and ameliorated the abnormal behaviors in VPA-induced ASD rats, in part, by activating the PI3K/Akt signaling pathway.

Development and validation of a pulmonary complications prediction model based on the Yang's index.

Background: Blunt chest trauma patients with pulmonary contusion are susceptible to pulmonary complications, and severe cases may develop respiratory failure. Some studies have suggested the extent of pulmonary contusion to be the main predictor of pulmonary complications. However, no simple and effective method to assess the severity of pulmonary contusion has been available yet. A reliable prognostic prediction model would facilitate the identification of high-risk patients, so that early intervention can be given to reduce pulmonary complications; however, no suitable model based on such an assumption has been available yet. Methods: In this study, a new method for assessing lung contusion by the product of the three dimensions of the lung window on the computed tomography (CT) image was proposed. We conducted a retrospective study on patients with both thoracic trauma and pulmonary contusion admitted to 8 trauma centers in China from January 2014 to June 2020. Using patients from 2 centers with a large number of patients as the training set and patients from the other 6 centers as the validation set, a prediction model for pulmonary complications was established with Yang's index and rib fractures, etc., being the predictors. The pulmonary complications included pulmonary infection and respiratory failure. Results: This study included 515 patients, among whom 188 developed pulmonary complications, including 92 with respiratory failure. Risk factors contributing to pulmonary complications were identified, and a scoring system and prediction model were constructed. Using the training set, models for adverse outcomes and severe adverse outcomes were developed, and area under the curve (AUC) of 0.852 and 0.788 were achieved in the validation set. In the model performance for predicting pulmonary complications, the positive predictive value of the model is 0.938, the sensitivity of the model is 0.563 and the specificity of the model is 0.958. Conclusions: The generated indicator, called Yang's index, was proven to be an easy-to-use method for the evaluation of pulmonary contusion severity. The prediction model based on Yang's index could facilitate early identification of patients at risk of pulmonary complications, yet the effectiveness of the model remains to be validated and its performance remains to be improved in further studies with larger sample sizes.

GM1 Reduced the Symptoms of Autism Spectrum Disorder by Suppressing α-Syn Through Activating Autophagy.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that cannot be cured. The ASD rat model was developed in this study to demonstrate the role and mechanism of ganglioside GM1 (GM1). Rats were given valproic acid (VPA) to create the ASD rat model. The rats' behaviors were assessed using the Y-maze test, open-field test, three-chamber social interaction test, and Morris water maze test. Relative levels of glutathione (GSH), malondialdehyde (MDA), catalase (CAT), reactive oxygen species (ROS), and superoxide dismutase (SOD) were quantitated using relative kits. Nissl, TUNEL, immunofluorescent, and immunohistochemistry staining techniques were used. GM1 treatment improved the ASD model rats' behavior disorders, including locomotor activity and exploratory behavior, social interaction, learning and memory capacity, and repetitive behavior. Following GM1 injection, striatal neurons grew and apoptosis decreased. GM1 reduced the excessively elevated α-Syn in ASD by encouraging autophagy. The behavior disorder of ASD model rats was exacerbated by autophagy inhibition, which also increased α-Syn levels. By increasing autophagy, GM1 reduced α-Syn levels and, ultimately, improved behavioral abnormalities in ASD model rats.

A Meta-Analysis on the Impact of Prenatal and Early Childhood Antimicrobial Use on Autism Spectrum Disorders.

OBJECTIVE: To investigate the impact of prenatal and early childhood antimicrobial use on autism spectrum disorders (ASD). DATA SOURCES: We searched PubMed and Embase databases for relevant studies from inception to August 2022. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed, observational studies were all acceptable. Raw data were extracted into a predefined worksheet and quality analysis was performed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Nineteen studies were identified in the meta-analysis. Prenatal antimicrobial exposure was not associated with ASD (P = 0.06 > 0.05), whereas early childhood antimicrobial exposure was associated with an increased odds ratio of ASD (OR = 1.17, 95% CI = [1.08-1.27], P value < 0.001). The sibling-matched analysis, with a very limited sample size, suggested that neither prenatal (P = 0.47 > 0.05) nor early childhood (P = 0.13 > 0.05) antimicrobial exposure was associated with ASD. Medical professionals may need to take the possible association into consideration when prescribing an antimicrobial in children. CONCLUSIONS: Early childhood antimicrobial exposure could increase the incidence of ASD. In future studies, it would be necessary to control for confounding factors, such as genetic factors, parenteral age at birth, or low birthweight, to further validate the association.

TCHis mitigate oxidative stress and improve abnormal behavior in a prenatal valproic acid-exposed rat model of autism.

Troxerutin is known for its anti-inflammatory and antioxidative effects in nerve impairment. The purpose of this study is to investigate the effect of troxerutin and cerebroprotein hydrolysate injections (TCHis) on prenatal valproic acid (VPA)-exposed rats. The VPA was administered to pregnant rats on gestational day 12.5 to induce a model of autism. The offspring were given the treatment of TCHis on postnatal day (PND) 21-50. On PND 43-50, the behavioral analysis of offspring was performed after the treatment of TCHis for 1 h. On PND 50, the offspring were harvested and the brains were collected. The hippocampus and prefrontal cortex were isolated for relevant biochemical detections. The administration of TCHis increased pain sensitivity and improved abnormal social behaviors in prenatal VPA-exposed rats. Prenatal exposure of VPA induced neuronal loss and apoptosis, enhanced reactive oxygen species (ROS) production, and promoted oxidative stress in hippocampus and prefrontal cortex, whereas these effects were reversed by the postnatal treatment of TCHis. In addition, postnatal administration of TCHis ameliorated mitochondrial function in hippocampus and prefrontal cortex of prenatal VPA-exposed rats. This study concluded that postnatal treatment of TCHis reduced oxidative stress and ameliorated abnormal behavior in a prenatal VPA-induced rat model of autism.

Efficacy and safety of single-dose antiviral drugs for influenza treatment: A systematic review and network meta-analysis.

To conduct network meta-analysis (NMA) of clinical efficacy and safety of single-dose antiviral drugs, grouped by dosage, in treatment of influenza. Systematic retrievals were conducted in databases, including Pubmed, Embase, Web of Science, the Cochrane Register of Clinical Trials and from the website ClinicalTrials.gov, for clinical trials recorded between the interception of the databases and March 31, 2021. Randomized controlled trials (RCTs) of influenza treatment in which single-dose antiviral drugs were administered were selected according to preset inclusion and exclusion criteria by two researchers who screened the literature independently from each other. The quality of the included studies was assessed using the Cochrane bias risk assessment tool. Software such as Stata 16.0 and Review Manager 5.3 was adopted for statistical analysis. Pairwise meta-analysis and NMA were carried out under the random-effects model. For both binary and continuous variables, odds ratio (OR), mean difference (MD) and their 95% confidence intervals (CI) were used to rank treatment efficiencies and analyze the differences. A total of 12 RCTs involving 7296 participants were included in the analysis. According to the NMA results, peramivir 300 mg (MD = -17.68, 95% CI: [-34.05, -1.32]), peramivir 600 mg (MD = -16.15, 95% CI: [-29.35, -2.95]), baloxavir (MD = -14.67, 95% CI: [-26.75, -2.58]) and laninamivir 40 mg (MD = -12.42, 95% CI: [-22.53, -2.31]) remarkably outperformed laninamivir 20 mg in time to alleviation of symptoms (TTAS). However, no intervention statistically outperform others in antipyretic time, virus titer variations against the baseline 24 and 48 h after medication and adverse events (AEs). The efficacy rankings were: peramivir 300 mg (the surface under the cumulative ranking curve [SUCRA] = 80.3%) > peramivir 600 mg (SUCRA = 76.2%) > baloxavir (SUCRA = 68.4%) > laninamivir 40 mg (SUCRA = 55.0%) > laninamivir 20 mg (SUCRA = 16.6%) for TTAS; baloxavir (SUCRA = 76.3%) > peramivir 600 mg (SUCRA = 67.8%) > laninamivir 40 mg (SUCRA = 47.2%) > laninamivir 20 mg (SUCRA = 40.0%) for antipyretic time; baloxavir (SUCRA = 96.7%) > peramivir 300 mg (SUCRA = 64.5%) ≈ peramivir 600 mg (SUCRA = 63.2%), baloxavir (SUCRA = 93.2%) > peramivir 600 mg (SUCRA = 64.0%) ≈ peramivir 300 mg (SUCRA = 55.0%), for virus titer variations against the baseline 24 and 48 h after medication, respectively; and baloxavir (SUCRA = 83.4%) > peramivir 300 mg (SUCRA = 71.4%) > laninamivir 20 mg (SUCRA = 62.4%) > peramivir 600 mg (SUCRA = 56.2%) > laninamivir 40 mg (SUCRA = 36.8%) for adverse events. Among the single-dose anti-influenza virus drugs compared, peramivir is superior to baloxavir and laninamivir in TTAS, whereas baloxavir has the best efficacy in antipyretic time, virus titer variations against the baseline 24 and 48 h after medication and AEs. This study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO), with a registration number of CRD42021238220.

Electroacupuncture at Zusanli ameliorates the autistic-like behaviors of rats through activating the Nrf2-mediated antioxidant responses.

OBJECTIVE: Emerging evidence suggests that acupuncture plays a neuroprotective role in autism. This study aimed to explore the effect of electroacupuncture at Zusanli (ST36) on autistic-like behaviors and the underlying mechanism. METHOD: Pregnant rats were administered with valproic acid (VPA) on gestational day 12.5 to induce an autism spectrum disorder (ASD) model. The pups were given electroacupuncture at ST36 daily from postnatal day (PND) 28-48. On PND28, the adenoviral vector containing small interfering RNA Nrf2 (Ad-siRNA-Nrf2) was injected into the prefrontal cortex of rats. The behavioral analysis was performed on PND 44-48. On PND48, the animals were euthanized and the brains were collected for further detection. Nissl staining was performed to detect neuronal viability. The biochemical markers of oxidative stress were subsequently measured. RESULT: Electroacupuncture at ST36 ameliorated the locomotor activity, social behavior, spatial learning and memory and repetitive behavior compared with ASD rats. It was notable that the electroacupuncture decreased oxidative stress markers in the tissues of prefrontal cortex, enhanced translocation of nuclear factor erythroid2-related factor2 (Nrf2) from cytoplasm to nucleus, and up-regulated the levels of NADP(H) quinone oxidoreductase (NQO1) and heme oxygenase (HO-1). However, these effects induced by electroacupuncture at ST36 were abolished after injection of Ad-siRNA-Nrf2. CONCLUSION: These data suggested that electroacupuncture at ST36 protected nerve function in ASD rats through Nrf2 activation and the antioxidant response.

Surgical treatment of costal cartilage fractures with titanium plate internal fixation.

BACKGROUND: This study aim to evaluate surgical procedures for titanium plate internal fixation of costal cartilage fractures with displacement or nonunion. METHODS: From January 2019 to October 2020, 13 patients with costal cartilage fractures were treated with titanium plate internal fixation in the thoracic surgery department of the Shanghai Sixth People's Hospital. Pain severity scale scores and respiratory function were evaluated preoperatively and postoperatively. All the patients had a 6-month follow-up for treatment evaluation. RESULTS: The mean hospital length of stay was 10.7 days. A statistically significant difference (P < 0.05) was found between preoperative and postoperative pain severity scores (7.69 vs. 5.00). VC (24.6% vs. 44.5%) and FEV1 (25.3% vs. 44.0%) were also significantly different before operation and after operation (P < 0.05). At follow-up, healing of the nonunion or fracture was confirmed in all the cases. CONCLUSION: The rigid titanium plate application ensured a safe and easy management of costal cartilage fractures and nonunion with a good prognosis as compared with other methods.

Estimation of 24-h Urine Protein Excretion Using Urine Albumin-to-Creatinine Ratio from an In-Hospital Population.

BACKGROUND There is little information available on quantitative description of the relationship between urine albumin-to-creatinine ratio (ACR) and 24-h urine protein excretion (24-h UPE). Here, we developed a calculation tool for 24-h UPE using the urine ACR and limited information on the request form. MATERIAL AND METHODS This was a retrospective and observational study. All individuals with same-day urine ACR and 24-h UPE tests in Sichuan Provincial People's Hospital from September 1, 2018 to December 31, 2019 were enrolled. Correlation and agreement between urine ACR and 24-h UPE were evaluated using correlation analysis and an intraclass correlation coefficient, respectively. The Durbin-Watson test and ANOVA were used to assess the performance of the calculation tool, and reliability of the prediction equation was evaluated in the validation group using residual error analysis. RESULTS A total of 906 participants were enrolled, including 639 participants in the development group and 267 in the validation group. Natural logarithm transformation was applied to remove skewness. Natural logarithm-transformed urine ACR correlated well with natural-logarithm-transformed 24-h UPE (Pearson coefficient=0.908; P<0.001) and the agreement was consistently good (overall ICC=0.938; 95% CI: 0.928-0.947; P<0.001). The multivariable regression model had good performance (R²=0.864) and high accuracy, demonstrated by results of residual error analysis. CONCLUSIONS We provide a practical calculation tool to estimate total protein excretion using urine ACR and readily accessible variables. However, 24-h UPE is still mandatory when proteinuria is over 10 g/day or when most proteinuria may not be of glomerular origin.

Preliminary Safety and Potential Effect of 6B11-OCIK Adoptive Cell Therapy Against Platinum-Resistant Recurrent or Refractory Ovarian Cancer.

Ovarian cancer is a leading cause of death among gynecological malignancies, and novel therapies are urgently needed. Here we report preliminary findings on the potential safety and efficacy of 6B11-OCIK, an adoptive cell therapy of autologous T cells induced by the humanized anti-idiotypic antibody 6B11 minibody plus dendritic cells and cytokines, against platinum-resistant recurrent or refractory ovarian cancer in three patients. We found that 6B11-OCIK treatment was safe and well tolerated after five cycles of intravenous infusion with an initial dose of 1-2×109 cells and a dose-climbing strategy. Hemoglobin, platelets, white cell count, creatinine or liver enzyme values, coagulation function, kidney and heart function were not significantly affected over the duration of therapy. Two of the three enrolled patients showed potentially drug-related grade 1 and 2 weakness, and no other adverse events were observed. Of the three enrolled patients, one had stable disease and two showed disease progression. The patient with favorable clinical efficacy had better immune response as measured by 6B11-OCIK proliferation capacity, activation ability of CD3+CD8+ tumor-specific cytotoxic T lymphocytes and CD3+CD56+ cytokine-induced killer cells, and tumor cell killing efficiency. Changes in circulating tumor cells after treatment were consistent with serum level CA125 in the patient with stable disease (both decreased), while differences were observed in the two patients with disease progression (increased CA125 in both and decreased CTC in the patient with better immune response), suggesting that variation of circulating tumor cells was more consistent with immune response and reflected efficacy directly. This preliminary study suggested that autologous 6B11-OCIK treatment was safe and had potential clinical efficacy against ovarian cancer. Patients with better immune response had more favorable efficacy. In addition to imaging, CA125 and immunophenotypes, CTC monitoring may represent a potential indicator of immunotherapy response.

[Method of Identifying Male Lineages Based on Main Haplotype and Analysis of the Distribution of Y-STR Haplotype Mismatch Based on the Bayesian Theory].

OBJECTIVE: To establish a classification method to identify different male lineages in a large population, to study the distribution patterns of Y-STR loci mismatches among Han Chinese male lineage members and to explore the mismatch probability distribution among the members with different meiosis intervals in the family. METHODS: Peripheral blood samples of 269 male individuals from 12 lineages in Han Chinese population and 45 unrelated male individuals were collected. Then, Yfiler Plus TM and ZGWZ FSY or Yfiler Platinum amplification kits were used, obtaining 314 Y-STR haplotypes. The Y-STR haplotype with 3 or more repetitions were selected as the main haplotype, in which the largest number was selected as the first data center. According to the standard of Y-STR genotype, those with mismatches within five loci and six steps were clustered and merged. Then, the main haplotype of the largest number in the remaining data was taken as the second data center, and cluster analysis is carried out in turn until there is no main haplotype remained. Pair comparison was conducted between lineage members and unrelated individuals, and the mismatch distribution among lineage members and unrelated individuals was calculated respectively. The average mismatch rate of each locus was subsequently calculated, as well as the mismatch probability distribution among members with different meiosis intervals within the lineage. RESULTS: 269 out of the 314 individuals were divided into 12 groups by cluster analysis method, accomplishing 100% accuracy between the cluster groups thus identified and the 12 known lineages. The remaining 45 unrelated individuals were scattered. The mismatch loci was within 0-7 loci and 0-7 steps among lineage members and the mismatch between unrelated individuals was at least 11 loci and 15 steps. The mismatch loci with the largest number of one-step and two-step mismatch were different in each lineage and had features that were specific to each lineage. The minimum mutation count and average mismatch rate of each locus were significantly correlated with the mutation rate. Two individuals with no mismatch had a 19.7% probability of 1 meiosis interval and a 71.2% probability of less than 6 meiosis interval. Two individuals with 3 loci mismatches had a 65.2% probability of more than 10 meiosis intervals. CONCLUSION: The cluster analysis method based on main haplotypes provided in this paper can quickly and effectively differentiate large male lineage samples. The clustering method and the mismatch probability distribution of different meiosis intervals obtained thus can provide new ideas for research and screening instruments, and important reference for lineage investigation, data analysis and practical application of Y-STR database in the future.

A case of thoracic aortic injury caused by multiple rib fractures.

Thoracic aortic injury is fatal but rare in blunt chest trauma, which usually requires urgent surgical treatment. It is mostly caused by posterior rib fractures. Chest wall stabilization (CWS) has been widely performed in patients with multiple rib fractures all over the world in the past two decades with satisfactory outcomes. However, the surgical treatment of posterior rib fracture within 2-3 cm from transverse process is still a difficult problem for thoracic surgeons. Under this circumstance, rib-transverse process internal fixation method was developed and widely performed for above patients at present. In this article, we presented a case of thoracic aortic injury caused by multiple rib fractures. A 54-year-old female was admitted to our hospital with dyspnea and severe chest pain caused by a falling object. Thoracic aortic injury with multiple rib fractures were diagnosed basing on image date and emergency CWS was performed for this patient. Rib-transverse process internal fixation was not performed in this case since the patients combined with transverse process fracture. We firstly performed transverse process resection combined with CWS for this patient. The results of our study showed this method is safe and feasible for patients with multiple rib fractures combined with transverse process fracture.