General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain.

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Impact of antifibrotic therapy on disease progression, all-cause mortality, and risk of acute exacerbation in non-IPF fibrosing interstitial lung diseases: evidence from a meta-analysis of randomized controlled trials and prospective controlled studies.

BACKGROUND: Nintedanib and pirfenidone are preferred pharmacological therapies for patients with idiopathic pulmonary fibrosis (IPF). However, evidence favoring antifibrotic therapy in patients with non-IPF fibrosing interstitial lung diseases (ILD) is limited. OBJECTIVE: To investigate the effects of antifibrotic therapy on disease progression, all-cause mortality, and acute exacerbation (AE) risk in patients with non-IPF fibrosing ILDs. DESIGN: Meta-analysis. DATA SOURCES AND METHODS: Electronic databases were searched for articles published before 28 February 2023. Studies that evaluated the efficacy of antifibrotic agents in patients with fibrosing ILDs were selected. The primary outcome was the disease progression risk, and the secondary outcomes included all-cause mortality and AE risk. The GRADE criteria were used for the certainty of evidence assessment. RESULTS: Nine studies with 1990 participants were included. Antifibrotic therapy reduced the rate of patients with disease progression (five trials with 1741 subjects; relative risk (RR), 0.56; 95% CI, 0.42-0.75; p < 0.0001; I2 = 0; high-certainty evidence). Antifibrotic therapy did not significantly decrease all-cause mortality (nine trials with 1990 subjects; RR, 0.76; 95% CI, 0.55-1.03; p = 0.08; I2 = 0; low-certainty evidence). However, in patients with progressive fibrosing ILDs (PF-ILD), antifibrotic therapy decreased all-cause mortality (four trials with 1100 subjects; RR, 0.69; 95% CI, 0.48-0.98; p = 0.04; I2 = 0; low-certainty evidence). CONCLUSION: Our study supports the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. TRIAL REGISTRATION: This study protocol was registered with PROSPERO (registration number: CRD42023411272).

Safety, immunogenicity, and efficacy of a modified COVID-19 mRNA vaccine, SW-BIC-213, in healthy people aged 18 years and above: a phase 3 double-blinded, randomized, parallel controlled clinical trial in Lao PDR (Laos).

Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos. Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital. The primary outcomes were safety and immunogenicity, with efficacy as an exploratory endpoint. Participants who were fully immunized with a two-dose inactivated vaccine for more than 6 months were assigned equally to either the SW-BIC-213 group (25 µg) or BBIBP group. The primary safety endpoint was to describe the safety profile of all participants in each group up to 6 months post-booster immunization. The primary immunogenic outcome was to demonstrate the superiority of the neutralizing antibody response, in terms of geometric mean titers (GMTs) of SW-BIC-213, compared with BBIBP 28 days after the booster dose. The exploratory efficacy endpoint aimed to assess the relative efficacy of SW-BIC-213 compared to BBIBP against virologically confirmed symptomatic COVID-19 over a 6-month period. The trial was registered with ClinicalTrials.gov (NCT05580159). Findings: Between October 10, 2022, and January 13, 2023, 1200 participants were assigned to SW-BIC-213 group and 1203 participants in the BBIBP group. All adverse reactions observed during the study were tolerable, transient, and resolved spontaneously. Solicited local reactions were the main adverse reactions in both the SW-BIC-213 group (43.8%) and BBIBP group (14.8%) (p < 0.001). Heterologous boosting with SW-BIC-213 induced higher live virus neutralizing antibodies to SARS-CoV-2 wildtype and BA.5 strains with GMTs reaching 750.1 and 192.9 than homologous boosting with BBIBP with GMTs of 131.5 (p < 0.001) and 47.5 (p < 0.001) on day 29. The statistical findings revealed that, following a period of 14-day to 6-month after booster vaccination, the SW-BIC-213 group exhibited a relative vaccine efficacy (VE) of 70.1% (95% CI: 34.2-86.4) against symptomatic COVID-19 when compared to the BBIBP group. Interpretation: A heterologous booster with the COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and proves highly immunogenic and efficacious in preventing symptomatic COVID-19 in individuals who have previously received two doses of inactivated vaccine. Funding: Shanghai Strategic Emerging Industries Development Special Fund, Biomedical Technology Support Special Project of Shanghai "Science and Technology Innovation Action Plan", Shanghai Municipal Science and Technology Commission.

Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults: an open-labeled, two-centered and multi-arm randomised, phase 1 trial.

BACKGROUND: We assessed the safety and immunogenicity of a core-shell structured lipopolyplex (LPP) based COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults. METHODS: We conducted an open-labeled, two-centered, and three-arm randomised phase 1 trial. Healthy adults, who had completed a two-dose of inactivated COVID-19 vaccine for more than six months, were enrolled and randomized to receive a booster dose of COVILO (inactivated vaccine) (n = 20) or SW-BIC-213-25µg (n = 20), or SW-BIC-213-45µg (n = 20). The primary study endpoint was adverse events within 30 days post-boosting. The secondary endpoint was the titers of binding antibodies and neutralizing antibodies against the wild-type (WT) of SARS-CoV-2 as well as variants of concern in serum. The exploratory endpoint was the cellular immune responses. This trial was registered with http://www.chictr.org.cn (ChiCTR2200060355). FINDINGS: Between Jun 6 and Jun 22, 2022, 60 participants were enrolled and randomized to receive a booster dose of SW-BIC-213 (25 µg, n = 20, or 45 µg, n = 20) or COVILO (n = 20). The baseline demographic characteristics of the participants at enrollment were similar among the treatment groups. For the primary outcome, injection site pain and fever were more common in the SW-BIC-213 groups (25 µg and 45 µg). Grade 3 fever was reported in 25% (5/20) of participants in the SW-BIC-213-45µg group but was resolved within 48 h after onset. No fatal events or adverse events leading to study discontinuation were observed. For secondary and exploratory outcomes, SW-BIC-213 elicited higher and longer humoral and cellular immune responses than that in the COVILO group. INTERPRETATION: SW-BIC-213, a core-shell structured lipopolyplex (LPP) based mRNA vaccine, was safe, tolerable, and immunogenic as a heterologous booster in healthy Chinese adults. FUNDING: Shanghai Municipal Government, the Science and Technology and Economic Commission of Shanghai Pudong New Area, and mRNA Innovation and Translation Center of Shanghai.

Exploring the Mechanism Whereby Sinensetin Delays the Progression of Pulmonary Fibrosis Based on Network Pharmacology and Pulmonary Fibrosis Models.

The incidence of pulmonary fibrosis (PF), a progressively fatal disease, has increased in recent years. However, there are no effective medicines available. Previous results have shown that sinensetin probably has some curative effects on PF. Therefore, this paper aims to predict the targets of sinensetin using a network pharmacology method and to confirm its effects and functional targets in PF using a mouse PF model. First, network pharmacology analysis showed that sinensetin has 105 functional targets, and 1,698 gene targets closely relate to PF. The intersection of the functional targets and gene targets produced 52 targets for the treatment of PF with sinensetin. The PPIs (protein-protein interactions) led to several potential key target genes, including MAPK1, EGFR, SRC, and PTGS2. The results of GO and KEGG analyses suggested the crucial function of apoptosis in PF and its involvement in the PI3K signaling pathway. Subsequently, we tested the molecular docking of sinensetin with the PI3K protein using the AutoDock4 software. The results showed that sinensetin could fit well into several binding sites of the PI3K protein. Furthermore, we constructed a PF mouse model through one-off intratracheal instillation of bleomycin and then intragastrically administered different concentrations of sinensetin to the model mice. Twenty-eight days later, the mice were sacrificed, and the lung tissues, serum, and bronchoalveolar lavage fluid (BALF) were collected. The in vivo tests showed that the body weight of model mice increased slightly compared with that of PF mice after intragastric sinensetin. HE and Masson staining suggested a certain extent of reduction in the pathology of lung tissues. The expression of collagens I and III, as well as hydroxyproline in the lung tissues, was reduced to a certain extent. IL-6 levels in the serum and BALF decreased markedly. The expression of vimentin and α-SMA in pulmonary tissues decreased. Cell apoptosis, as well as P-PI3K and P-AKT levels, in lung tissues also reduced. In summary, network pharmacology and in vivo test results suggest sinensetin causes an effective delay in the progression of pulmonary fibrosis, and the functional mechanism is likely related to PI3K-AKT signaling.

Spinal muscular atrophy complicated with pulmonary infection:A clinical analysis of 36 children / 中国实用儿科杂志

OBJECTIVE: To summarize the clinical features of spinal muscular atrophy complicated with pulmonary infection in children,and to improve clinicians' understanding of the disease and improve the prognosis. METHODS: The clinical data of 36 children with SMA complicated with pulmonary infection,who were admitted to Yuying Children's Hospital of the Second Affiliated Hospital of Wenzhou Medical University from January 1,2008 to December 31,2017,were retrospectively analyzed. RESULTS: Among of the 36 patients,19 were typeⅠ,9 were typeⅡ,and 8 were typeⅢ. The common clinical manifestations and signs were fever,cough,shortness of breath,laborious breathing,three-concave signs,and crackles in the lungs. Respiratory failure occurred in 11 children,including 7 children(63.6%)with typeⅠSMA,2 children(18.2%)with typeⅡ SMA and 2 children(18.2%)with typeⅢ SMA. Imaging findings showed 5 cases of scoliosis,3 cases being typeⅡ SMA,and 2 being typeⅢ SMA. Pathogenic tests were positive in 18 children:10 cases(55.5%)of type Ⅰ SMA,4 cases(22.2%)of typeⅡ SMA,4 cases(22.2%)of typeⅢ SMA;nosocomial mixed infection with conditioned pathogens was common,among which Burkholderia cepacia was the most common. Three patients died in the hospital,22 patients improved and discharged,and the remaining 11 patients gave up treatment. The number of hospitalizations,the incidence of severe pneumonia and respiratory failure was significantly different between the first 5 years(2008-2012)and the last 5 years(2013-2018)(P<0.05). CONCLUSION: SMA is verysusceptible to pulmonary infection. We should be alert to opportunistic pathogenic bacteria infection and use mechanical ventilation in time for respiratory failure patients. Active and effective respiratory care can reduce the incidence of pulmonary infection and improve the prognosis of SMA children.

Electric bicycle cost calculation models and analysis based on the social perspective in China.

Electric bicycles (EBs) are increasingly popular around the world. In April 2014, EB ownership in China reached 181 million. While some aspects of the impact of EBs have been studied, most of the literature analyzing the cost of EBs has been conducted from the buyer's point of view and the perspective of social cost has not been covered, which is therefore the focus of this paper. From the consumer's point of view, only the costs paid from purchase until retirement are included in the cost of EBs, i.e., the EB acquisition cost, battery replacement cost, charging cost, and repair and maintenance cost are included. Considered from the perspective of the social cost (including impact on the environment), costs that are not paid directly by consumers should also be included in the cost of EBs, i.e., the lead-acid battery scrap processing cost, the cost of pollution caused by wastewater, and the traffic-related costs. Data are obtained from secondary sources and surveys, and calculations demonstrate that in the life cycle of an EB, the consumer cost is 6386.2 CNY, the social cost is 10,771.2 CNY, and the ratio of consumer to social cost is 1:1.69. By comparison, the ratio for motor vehicles is 1:1.06, so that the share of the life cycle cost of EBs that is not borne by the consumer is much higher than that for motor vehicles, which needs to be addressed.

Effect of curcumin on expression of SLPI,TNF-αand IL-1βin BEAS-2B cells induced by Streptococcus pneumoniae / 中国病理生理杂志

AIM:To explore the effect of curcumin(Cur)and curcuminoids(Y20 and 6B)on the expression of secretory leukocyte protease inhibitor(SLPI), tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)induced by Streptococcus pneumoniae(SP)and the possible mechanism.METHODS:BEAS-2B cells incubated with SP were set up as an inflammation model of pneumonia.The mRNA levels of SLPI at 1 h,3 h,6 h and 9 h,and the mRNA expression of TNF-αand IL-1βat 3 h,6 h and 9 h in control group,SP infection group,Cur treatment group,Y20 treatment group and 6B treatment group were measured by qPCR.The protein levels of TNF-αand IL-1βin the culture supernatant were measured by ELISA.The protein levels of Toll-like receptor 2(TLR2)and phosphorylated nuclear factor-κB(p-NF-κB) p65 at 3 h,6 h and 9 h were determined by Western blot.RESULTS:The mRNA level of SLPI was increased in Cur, Y20 and 6B treatment groups compared with SP group(P<0.05).The protein levels of TLR2 and p-NF-κB p65 were sig-nificantly increased after SP stimulation.After treatment with Cur,Y20 and 6B,the protein levels of TLR2 and p-NF-κB p65 were significantly decreased(P<0.05).The levels of TNF-αand IL-1βwere significantly increased after SP stimula-tion.Cur,Y20 and 6B significantly decreased the levels of TNF-αand IL-1βin the supernatant(P<0.05).CONCLU-SION: Cur, Y20 and 6B increase SLPI expression, reduce the expression of inflammatory cytokines TNF-αand IL-1β. The possible mechanism might be associated with inhibiting TLR 2 expression and down-regulating the transcriptional activity of NF-κB.

Effect of Qijingmingmu decoction granule on MAPK signal pathway in fibroblasts of conjunctivochalasis stimulated by TNF-α / 眼科新进展

Objective To observe the effects of Qijingmingmu decoction granule on the expression of mitogen-activated protein linase (MAPK) signal pathway in fibroblasts of conjunctivochalasis (CCH) under the stimulation of tumor necrosis factor (TNF-α) and to explore the pathogenesis and effective treatment method of CCH.Methods CCH conjunctival fibroblasts were cultured in vitro and divided into CCH group,CCH + TNF-α group and CCH + TNF-α + Qijingmingmu decoction group.CCK-8 assay was used to determine the effective concentration of Qijingmingmu decoction granule,and 10-2 mg · L-1 TNF-α was added in the cultured fibroblasts of the latter two groups,followed by interference with Qijingmingmu decoction granule for 48h.The expression of MAPK signal pathway related protein and mRNA were detected by ELISA,Western Blot and RT-PCR.Then the results were statistically analyzed.Results CCK-8 assay showed the effective concentration of Qijingmingmu decoction granule was 1.61g · L-1.And there were significant differences in the total A values (A450) of extracellular regulated protein kinase (ERK),c-jun N-terminal kinase (JNK),p38 mitogen activated protein kinase (p38 MAPK) and their phosphorylation levels among the three groups (all P ＜ 0.05).Moreover,TNF-α could significantly up-regulate the expression of ERK1/2,JNK1/2,p-JNK1/2,p38 MAPK and p-p38 MAPK in CCH fibroblasts (all P ＜0.05),while Qijingmingmu decoction down-regulated their expressions in CCK fibroblasts after TNF-α stimulation (all P ＜ 0.05).Furthermore,the total differences in p-ERK1/2,p38 MAPK and p-p38 MAPK protein were significant in the three groups (all P＜0.05);and TNF-α could significantly up-regulate the expression of p-ERK1/2,p-JNK1/2,p38 MAPK and p-p38 MAPK protein in CCH fibroblasts (all P ＜0.05),while Qijingmingmu decoction down-regulated p-ERK1/2 and p38 MAPK expressions in CCK fibroblasts after TNF-α stimulation (both P ＜ 0.05).In addition,the total differences in ERK1/2 and p38 MAPK mRNA were significant in the three groups (both P ＜ 0.05);and TNF-α could significantly up-regulate the expression of ERK1/2 and p38 MAPK mRNA in CCH fibroblasts (both P ＜ 0.05),while Qijingmingmu decoction down-regulated p38 MAPK mRNA expressions in CCK fibroblasts after TNF-α stimulation (P ＜ 0.05).Conclusion The inflammatory factor TNF-α can up-regulate the expressions of MAPK signal pathway related protein and mRNA in CCH fibroblasts,resulting in the occurrence and development of CCH,and meanwhile Qijingmingmu decoction granule can downregulate the expression of MAPK signal pathway to play the therapeutic role in CCH to some extent.

Clinical characteristics of children with Streptococcus pneumoniae septicemia and drug sensitivity of Streptococcus pneumoniae / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of children who suffered from Streptococcus pneumoniae (SP) septicemia and the drug sensitivity of SP strains.</p><p><b>METHODS</b>A retrospective analysis was performed on the clinical data of 25 children with SP septicemia between January 2009 and December 2012.</p><p><b>RESULTS</b>Of the 25 cases, 16 (64%) were aged under 2 years, 5 (20%) were aged 2-5 years, and 4 (16%) were aged over 5 years. Fourteen cases (56%) were complicated by infection of other organs, and 5 cases (20%) had underlying chronic diseases. Fever was the most common clinical manifestation, and the majority presented with remittent fever. Eight patients with pneumonia or pyothorax had pulmonary symptoms. Five patients with purulent meningitis had neurological symptoms, five cases had hepatosplenomegaly and two cases had septic shock. Nineteen cases (76%, 19/25) had significantly elevated white blood cell (WBC) counts, twenty-one cases (84%, 21/25) had significantly elevated serum C-reactive protein (CRP) levels, and eight cases (50%, 8/16) had significantly elevated serum procalcitonin (PCT) levels. The drug sensitivity analysis showed that invasive SP had high resistance rates to penicillin (96%), clindamycin hydrochloride (88%) and erythromycin (84%), and it was completely sensitive to imipenem, vancomycin, levofloxacin and linezolid. The multi-drug resistance rate of invasive SP was up to 88%. Twenty-three cases (92%) were cured or improved after active treatment.</p><p><b>CONCLUSIONS</b>SP septicemia is commonly seen in children aged under 2 years. The most common clinical manifestation is fever, accompanied by elevated WBC count, CRP level and PCT level, and it is usually complicated by pulmonary or brain infection. Resistance to multiple antibiotics is very common in SP strains, so it is important to properly use antibiotics according to drug sensitivity test results. Patients who receive active treatment have a good clinical outcome.</p>

Janus-type AT nucleosides: synthesis, solid and solution state structures.

Novel Janus-type nucleoside analogues (1a-d) were synthesized. Their pyrimido[4,5-d]pyrimidine base moiety has one face with a bidentate Watson-Crick donor-acceptor (DA) H-bond array of adenine and the other face with an acceptor-donor (AD) H-bond array of thymine. These nucleosides may self-associate through the self-complementary base pair. Indeed, in the solid state, compound 6d displayed a honeycomb-like supramolecular structure with tetrameric membered cavities formed through the combination of reverse Watson-Crick base pairs and aromatic stacking, in which the solvent molecules were accommodated. The result of temperature-dependent CD studies showed that the free nucleosides can form higher order chiral structures in aqueous solution.

Emergency endovascular repair of complicated Stanford type B aortic dissections within 24 hours of symptom onset in 30 cases.

OBJECTIVE: To investigate the results of emergency endovascular repair of complicated Stanford type B aortic dissections within 24 hours of symptom onset. METHODS: A retrospective analysis of the clinical data of 30 patients with complicated Stanford type B aortic dissections who underwent emergency endovascular repair between June 2007 and October 2008. Endovascular repairs were performed within 24 hours of symptom onset. Stent-grafts were deployed at the first entry tear through the femoral artery under fluoroscopic guidance. Follow-up computed tomography scans were performed at 1, 3, 6, 12, and 18 months after treatment. RESULTS: The mean patient age was 64 years (range, 43-83 years). There were 3 cases associated with rupture, 6 cases associated with refractory hypertension, 15 cases associated with persistent pain, 2 cases associated with retrograde dissection, and 4 cases associated with malperfusion. The technical success rate was 100%, and the incidence of immediate postoperative endoleaks was 13.4%. One patient died of dissection rupture within 30 days. The mean follow-up period was 12 ± 8 months. A small, persistent endoleak (<10%) occurred in 1 patient, and 1 patient died of acute liver failure 2 months after the operation. No stent dislocation, false lumen expansion, or paraplegia occurred. The false lumen was completely thrombosed in 6 patients and partially thrombosed in 19 patients. The mortality rate was 6.67%. CONCLUSIONS: Our results suggest that emergency endovascular repair of complicated Stanford type B aortic dissections within 24 hours of symptom onset is associated with good outcomes and can decrease mortality.

Factors influencing the progression-free survival time of prostate cancer patients after endocrine therapy / 中华男科学杂志

<p><b>OBJECTIVE</b>The progression of prostate cancer (PCa) after endocrine therapy varies widely in different PCa patients. This study aims to analyze the factors that influence the progression-free survival time of PCa patients after endocrine therapy in an attempt to improve the prognosis of the disease.</p><p><b>METHODS</b>We reviewed the clinicopathological data of 116 cases of prostate cancer treated by endocrine therapy, analyzed the clinicopathological factors that influence the progression-free survival time of PCa patients using univariate (log-rank test) and multivariate Cox proportional hazard models, and investigated the correlation among these factors by Spearman rank correlation analysis.</p><p><b>RESULTS</b>In the stepwise Cox proportional hazard model, the independent prognostic factors for PCa progression after endocrine therapy were found to be Gleason score (P < 0.01) and clinical stages (P < 0.01). The hazard of PCa progression after endocrine therapy increased 2.126 times that of the baseline for each unit of increase in Gleason score, and 6.625 times for each unit of increase in the clinical stage. The pretreatment PSA level was correlated with both clinical stages (P < 0.01) and Gleason score (P < 0.01).</p><p><b>CONCLUSION</b>Clinical stages and Gleason score were important factors that influenced the progression-free survival time after endocrine therapy in this cohort of PCa patients.</p>

Expression of potential molecular markers in prostate cancer: correlation with progression in patients after endocrine therapy / 中华泌尿外科杂志

Objective To evaluate the expression of molecular markers in prostate cancer and to clarify the significance of these markers as prognostic indicators for androgen deprivation therapy. Methods A series of 116 prostate cancer patients under androgen deprivation therapy as a single treatment was reviewed. Expression levels of 7 proteins, including androgen receptor(AR),E-cadherin, Chromogranin A(CgA) , Ki-67, Survivin, EZH2 and hepsin, were measured by immunohistochemical staining. Results Of the 7 molecules. Ki67,EZH2 and Survivin expression were significantly associated with several conventional prognostic factors. Univariate analysis identified clinical stage, Glea-son scores,pretreatment serum PSA level, Ki-67 and Survivin expression as significant predictors for prostate-specific antigen (PSA) progression after endocrine therapy. Of these significant factors, Survivin expression, clinical stage and Gleason scores appeared to be independently related to PSA progression after endocrine therapy by multivariate analysis. Furthermore, there were significant differences in PSA progression-free survival according to positive numbers of these three independent risk factors. Conclusion Survivin could be a useful independent prognostic factor in prostate cancer with endocrine therapy, besides clinical stage and Gleason score.