OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To investigate the application effect of early awake prone position in mild-to-moderate acute respiratory distress syndrome (ARDS) patients, and analyze the related factors affecting the prone position outcome.Methods:A prospective cohort study was conducted. The mild-to-moderate ARDS patients admitted to the emergency department of Yingshang County People's Hospital from January 2020 to June 2023 were enrolled as the research subjects. According to the results of prone tolerance test, the patients were divided into awake prone position group and non-prone position group. All patients were given high flow nasal cannula (HFNC) according to the standard procedures. The patients in the awake prone position group received prone position treatment within 12 hours after admission, in addition to the standard treatment. This could be performed in several times, at least once a day, and at least 2 hours each time. In order to prolong the prone position as much as possible, the patients were allowed to move or keep a small angle side prone. The changes of oxygenation index (PaO 2/FiO 2) at 0, 24, 48, and 72 hours after admission, the rate of intensive care unit (ICU) transfer, the use rate and use time of non-invasive ventilation (NIV), the total hospital stay, and the daily prone position time and 2-hour ROX index [ratio of pulse oxygen saturation/fraction of inspired oxygen (SpO 2/FiO 2) and respiratory rate (RR)] of prone position patients were recorded. The successful termination of HFNC was defined as the successful prone position, and the failure of prone position was defined as switching to NIV or transferring to ICU. Subgroup analysis was performed, and the binary multivariate Logistic regression analysis was used to screen the influencing factors of the early awake prone position outcome. Results:A total of 107 patients were finally enrolled, with 61 in the awake prone position group and 46 in the non-prone position group. Both groups showed a gradual increase in PaO 2/FiO 2 with prolonged admission time. The PaO 2/FiO 2 at 24 hours after admission in the awake prone position group was significantly higher than that at 0 hour [mmHg (1 mmHg ≈ 0.133 kPa): 191.94±17.86 vs. 179.24±29.27, P < 0.05], while the difference in the non-prone position group was only statistically significant at 72 hours (mmHg: 198.24±17.99 vs. 181.24±16.62, P < 0.05). Furthermore, the PaO 2/FiO 2 at 48 hours and 72 hours after admission in the awake prone position group was significantly higher than that in the non-prone position group. The use rate of NIV in the awake prone position group was significantly lower than that in the non-prone position group [36.1% (22/61) vs. 56.5% (26/46), P < 0.05]; Kaplan-Meier curve analysis further confirmed that the patients in the awake prone position group used NIV later, and the cumulative rate of NIV usage was significantly lower than that in the non-prone position group (Log-Rank test: χ2 = 5.402, P = 0.020). Compared with the non-prone position group, the ICU transfer rate in the awake prone position group was significantly lowered [11.5% (7/61) vs. 28.3% (13/46), P < 0.05], and the HFNC time, NIV time, and total hospital stay were significantly shortened [HFNC time (days): 5.71±1.45 vs. 7.24±3.36, NIV time (days): 3.27±1.28 vs. 4.40±1.47, total hospital stay (days): 11 (7, 13) vs. 14 (10, 19), all P < 0.05]. Of the 61 patients who underwent awake prone positioning, 39 were successful, and 22 failed. Compared with the successful group, the patients in the failure group had a higher body mass index [BMI (kg/m 2): 26.61±4.70 vs. 22.91±5.50, P < 0.05], lower PaO 2/FiO 2, proportion of asymptomatic hypoxemia and 2-hour ROX index of prone position [PaO 2/FiO 2 (mmHg): 163.73±24.73 vs. 185.69±28.87, asymptomatic hypoxemia proportion: 18.2% (4/22) vs. 46.2% (18/39), 2-hour ROX index of prone position: 5.75±1.18 vs. 7.21±1.45, all P < 0.05], and shorter daily prone positioning time (hours: 5.87±2.85 vs. 8.05±1.99, P < 0.05). Binary multivariate Logistic regression analysis showed that all these factors were influencing factors for the outcome of awake prone positioning (all P < 0.05), among which BMI [odds ratio ( OR) = 1.447, 95% confidence interval (95% CI) was 1.105-2.063] and non-asymptomatic hypoxemia ( OR = 13.274, 95% CI was 1.548-117.390) were risk factors for failure of prone position, while PaO 2/FiO 2 ( OR = 0.831, 95% CI was 0.770-0.907), daily prone positioning time ( OR = 0.482, 95% CI was 0.236-0.924), and 2-hour ROX index of prone position ( OR = 0.381, 95% CI was 0.169-0.861) were protective factors. Conclusions:Early awake prone positioning in patients with mild-to-moderate ARDS supported by HFNC is safe and feasible, reducing the use rate and duration of NIV, lowering the ICU transfer rate, and shortening the hospital stay. High BMI and non-asymptomatic hypoxemia are risk factors for failed prone position, while higher PaO 2/FiO 2 and the ROX index within 2 hours of prone position (the patient's good response to prone position), and prolonged daily prone position can improve the success rate of prone position.

Objective:To evaluate the efficacy and safety of θ short burst rapid pulse stimulation(TBS)in treating schizophrenia by meta-analysis.Methods:Randomized controlled trials(RCTS)on TBS in the treatment of schizophrenia were searched from CNKI,Wanfang,VIP,China Biomedicine,Web of science,PubMed,Embase and Cochrane Library databases to December 2022.The main study indicator was the Positive and Negative Symptoms Scale(PANSS).Risk quality assessment of the included literatures was performed by two reviewers and statistical analysis was performed using RevMan5.3.Results:A total of 13 RCTS with 641 patients were included.Meta-anal-ysis showed that TBS targeting the left dorsolateral prefrontal cortex(DLPFC)with intervention duration longer than 2 weeks decreased the PANSS total scores(WMD=-4.63,95％CI:-5.75--3.51,P＜0.001),positive symptom scores(WMD=-1.13,95％CI:-2.00--0.26,P＜0.05),negative symptom scores(WMD=-2.51,95％CI:-2.77--1.53,P＜0.001)and general psychopathological symptom scores(WMD=-1.20,95％CI:-1.80--0.60,P＜0.001).The adverse reactions of TBS included dizziness,and no serious adverse e-vents were reported.Conclusion:TBS has high safety,and stimulation of left dorsolateral prefrontal cortex targets for more than 2 weeks could effectively improve psychiatric symptoms in patients with schizophrenia.

Objective:To analyze the screening test results of people infected with human immunodeficiency virus (HIV) in the window period confirmed to be "negative" by Western blotting, with a view to finding a way to identify people infected with HIV during the window period as soon as possible.Methods:In the serum (plasma) samples of HIV-positive people screened by the fourth-generation chemiluminescent immunoassay in medical institutions at all levels in Pudong New District, Shanghai from 2014 to 2021, a total of 100 people (200 samples) were confirmed as "negative" and the fourth-generation enzyme-linked immunosorbent assay was screened positive. According to the follow-up results, it was divided into the early infection group (24 cases) and the uninfected group (76 people), and the fourth-generation rapid diagnostic test (RDT) was performed. The compliance rates of positive results of screening and follow-up were compared, and the epidemiological data of early HIV infections were analyzed. The chi-square test was used for statistical analysis.Results:Of the 200 samples, 48(24.00%) were early infected. A total of 106 samples antigens and (or) antibodies were positive by the fourth-generation RDT screening, and the compliance rate with the follow-up results was 45.28%(48/106), of which those of the fourth-generation RDT screening antigen positive and follow-up results were 100.00%(36/36), which was higher than the antibody positive results (24.68%(19/77)). The difference was statistically significant ( χ2=57.49, P<0.001). Of the 24 cases of early HIV infections, 19(79.2%) had acute symptoms. Only one out of six people≥50 years old had asked about the partner about his HIV status before engaging high-risk sex, and 13 out of 18 people <50 years old had asked the partners about their HIV status or to detect HIV before engaging high-risk sex. The difference was statistically significant ( χ2=5.71, P=0.017). Out of the six people ≥50 years old, only one actively tested HIV, and 12 out of 18 people <50 years old actively tested HIV, and the difference was statistically significant ( χ2=4.53, P=0.033). Conclusions:The Western blotting confirmed "negative" samples may be false negative. The comprehensive evaluation which combined with the fourth-generation screening test could help to screen out HIV window infection. In addition, the publicity, education and monitoring of high-risk population need to be further strengthened.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.