ObjectiveTo investigate the therapeutic effects and mechanism of decoctions from four kinds of processed products of Aconiti Radix Lateralis Praeparata（ARLP） in deficiency-cold syndrome. MethodsA total of 36 SD rats were randomly divided into the control group， model group， Shengfupian（SFP） group， Paofuzi（PFZ） group， Heishunpian（HSP） group and Paofupian（PFP） group with 6 rats in each group. Except for the control group， rats in other groups were administered hydrocortisone sodium succinate via intramuscular injection to induce a cold deficiency syndrome model. After 14 consecutive days， each ARLP decoction pieces was administered via continuous gastric lavage at a dose of 12 g·kg^-1·d^-1 for 7 d， while the control and model groups received an equivalent volume of physiological saline. After the end of administration， body weight， spleen weight and thymus weight were measured for calculating the spleen and thymus indexes. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of adrenal tissue. The fully automatic biochemistry analyzer was used to measure the total cholesterol（TC）， triglyceride（TG）， lactic dehydrogenase（LDH） and lactate（LAC） levels in serum. Enzyme-linked immunosorbent assay（ELISA） was employed to measure the contents of 17-hydroxycorticosteroid（17-OHCS）， cortisol（CORT）， triiodothyronine（T₃）， thyroxine（T₄）， thyrotropin（TSH）， immunoglobulin（Ig） M， IgG， cyclic adenosine monophosphate（cAMP） and cyclic guanosine monophosphate（cGMP）. Western blot was used to measure the protein expression levels of protein kinase A（PKA）， cAMP response element-binding protein（CREB）， silent information regulator 1（Sirt1） and peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α）. And high performance liquid chromatography（HPLC） was used to determine the content of major alkaloids， followed by Pearson correlation analysis with pharmacodynamic indicators. ResultsAfter modeling， compare with the control group， the model rats exhibited symptoms such as lethargy and loose stools， mild abnormalities were observed in adrenal tissue structure， and both spleen and thymus indices were significantly reduced（P<0.01）. Thyroid， adrenal and immune system functions were suppressed， with decreased serum cAMP level and significantly elevated cGMP level（P<0.01）. Compared with the model group， the adrenal injury by hydrocortisone sodium succinate were repaired and the spleen index were increased significantly in all four ARLP groups（P<0.05， P<0.01）. The thymus index in SFP and PFZ groups were increased significantly（P<0.05）. The contents of T₃， TSH， 17-OHCS and CORT were increased significantly in SFP and PFZ groups（P<0.05）. In addition， the content of IgG in SFP， PFZ and PFP groups were increased significantly（P<0.01）， while the content of IgM in PFZ and HSP groups were also increased significantly（P<0.05）. Regarding the cyclic nucleotide system， PFZ significantly elevated cAMP level while reducing cGMP level（P<0.05）， exhibiting the most pronounced effect among the four decoction pieces. For energy metabolism indicators， PFZ significantly improved abnormal markers including TC， TG， LDH， and LAC（P<0.05）. HSP showed marked improvement effects on TG， LDH， and LAC（P<0.05）. Both PFZ and SFP significantly elevated the expression levels of PKA， CREB， Sirt1， and PGC-1α proteins（P<0.01）. Additionally， the diester alkaloids in ARLP showed a strong positive correlation with TG， IgG， and CORT， a strong negative correlation with LAC， a moderate positive correlation with T₄， and moderate negative correlations with cAMP and spleen index. Monomeric alkaloids showed strong positive correlations with TG and IgG， strong negative correlations with LAC， moderate positive correlations with CORT and T₄， and moderate negative correlations with cAMP and spleen index. However， the content of water-soluble alkaloids showed strong positive correlations with TC， LDH， 17-OHCS， T₃， TSH， and thymus index， moderate positive correlations with cAMP， CORT， T₄， and spleen index， and moderate negative correlation with cGMP. ConclusionAmong different processed ARLP decoction pieces， PFZ processed according to ZHANG Zhongjing's method exhibits the most potent warming and cold-dispelling effects. Its pharmacological actions are mediated through regulating the thyroid， adrenal， immune， cyclic nucleotide systems， and material-energy metabolism pathways. Among these， water-soluble alkaloids show strong or moderate correlations with more indicators of deficiency-cold syndrome and exhibit the highest content in PFZ. Therefore， PFZ processed according to ZHANG Zhongjing's method may exert its warming and cold-dispelling effects through water-soluble alkaloids.

Conducting ethical review of investigator-initiated trials （IIT） is one of the important links to ensure the quality of research projects. Currently， the quality of ethical review for IIT projects is greatly influenced by the personal factors of committee members， which to some extent affects the ethical review committee’s judgments of research risks and benefits. Based on the previously developed Risk-Benefit Assessment Scale for Clinical Research， this paper established an ethical review decision-making pathway based on risk-benefit assessment， that is， proposed the “four-step method” for ethical review risk-benefit assessment， including evaluating the research benefits， assessing the research risks， constructing a risk-benefit matrix， and establishing an ethical review pathway. The “four-step method” helps to reduce the impact of committee members’ subjective/intuitive judgments on the quality of ethical review， assists in promoting the implementation of multi-center ethical review policy， narrows the gap in the quality of ethical review among different medical institutions， and provides clearer guidance for the risk judgments of scientific research management and ethical review departments.

OBJECTIVE: To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC). METHODS: A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05). CONCLUSION Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans ; Acupuncture Points ; Gastroesophageal Reflux/physiopathology* ; Male ; Female ; Cough/physiopathology* ; Middle Aged ; Aged ; Acupuncture Therapy ; Adult ; Treatment Outcome ; Lung/physiopathology* ; Meridians

BACKGROUND: The correlation between the morphological structure of the patellofemoral joint (PFJ) and the severity of knee joint osteoarthritis (KOA) remains uncertain. This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs. METHODS: This multi-center, retrospective study analyzed the magnetic resonance imaging (MRI) scans and anteroposterior radiographs of 534 adult outpatients with KOA. To evaluate the radiographic severity of KOA, anteroposterior radiographs of the knee and the Kellgren-Lawrence (K-L) grade were used. Knee MRI scans were used to measure the patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt angle (LPTA), and the distance between tibial tuberosity and trochlear groove (TT-TG). We examined the association between the configuration of the PFJ, arrangement, and harshness of the KOA. Information on participants' demographics, such as age, sex, side, height, and weight, was collected. A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side. Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA. Multiple linear regression models were used for the association between LPTA, SA, TT-TG, and severity of KOA after accounting for demographic variables. RESULTS: The study comprised of 534 patients; of these, 339 (63%) were female. A total of 586 knees were evaluated in this study. Age showed a strong positive correlation with KOA severity ( r  = 0.516, P <0.01), whereas LPTA showed a strong negative correlation ( r  = -0.662, P <0.01). Additionally, SA ( r  = 0.616, P <0.05), and TT-TG showed a strong positive correlation ( r  = 0.770, P <0.01) with tibiofemoral osteoarthritis (TFOA) severity. Multiple linear regression analysis indicated that knee osteoarthritis severity (β = -2.946, P <0.001) and side (β = -0.839, P  = 0.001) was associated with LPTA; knee osteoarthritis severity (β = 5.032, P <0.001) and age (β = -0.095, P <0.001) was associated with SA; knee osteoarthritis severity (β = 2.445, P <0.001), sex (β = -0.326, P  = 0.041), body mass index (β = -0.061, P  = 0.017) and age (β = -0.025, P <0.001) was associated with TT-TG. CONCLUSION Radiographic severity of KOA was positively associated with age, SA, and TT-TG but negatively associated with LPTA.
Humans ; Female ; Male ; Osteoarthritis, Knee/pathology* ; Middle Aged ; Retrospective Studies ; Aged ; Patellofemoral Joint/pathology* ; Magnetic Resonance Imaging ; Adult ; Patella/pathology* ; Radiography

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Objective To compare the effect of routine speech training and computer-assisted training on post-stroke dysarthria. Methods From March,2021 to April,2023,72 patients with post-stroke dysarthria in Beijing Bo'ai Hospital were ran-domly divided into control group(n=36)and experimental group(n=36).Both groups received routine rehabili-tation,while the control group received routine speech training,and the experimental group received computer-assisted training,for four weeks.They were assessed with modified Frenchay Dysarthria Assessment(m-FDA)and Speech Intelligibility(SI)before and after intervention. Results Eight cases in the control group and one case in the experimental group dropped down.The scores of m-FDA and SI improved in both groups after treatment(|Z|＞4.183,P＜0.001),and there was no significant difference between two groups(|Z|＜1.598,P＞0.05).Noninferiority of m-FDA was found between two groups(|t|＞3.656,P＜0.001). Conclusion Computer-assisted training could improve the speech function of patients with post-stroke dysarthria,simi-lar to routine speech training.

OBJECTIVE To observe the clinical efficacy and safety of tofacitinib combined with hydroxychloroquine in the treatment of refractory rheumatoid arthritis （RA）. METHODS From January 1， 2021 to January 1， 2022， 120 patients with refractory RA were selected as the study objects. According to the principle of random allocation， the patients were divided into group A， group B and group C， with 40 patients in each group. Group A was given Tofacitinib citrate tablet + Hydroxychloroquine sulfate tablet； group B was given Tofacitinib citrate tablet + Methotrexate tablet； group C was given Tofacitinib citrate tablet + Leflunomide tablet. Three groups were given relevant medicine for 6 months. Therapeutic efficacy and disease activity score 28 （DAS 28） of 3 groups as well as Sharp score， the levels of biochemical indicators [erythrocyte sedimentation rate （ESR）， C- reactive protein （CRP）]， immune indexes [rheumatoid factor （RF）， anti-cyclic peptide containing citrulline （anti-CCP） antibody]， serum cytokine indicators [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] before and after treatment were observed； the occurrence of adverse drug reactions during treatment was recorded. RESULTS After treatment， the proportions of ACR50 and ACR70 patients in group A were significantly higher than groups B and C （P＜0.05）； DAS28 score， Sharp score， biochemical indicators， immune indexes and serum cytokine indicators of 3 groups were significantly lower than before treatment （P＜0.05）， and gradually decreased with prolonged treatment time； after 6 months of treatment， DAS28 score， Sharp score， RF， anti-CCP antibody， the levels of IL-6 and TNF-α in group A were significantly lower than group B and C （P＜0.05）. There was no significant difference in the incidence of diarrhea， nausea and vomiting， leukopenia， rash， abnormal liver and kidney function， or dizziness among 3 groups （P＞0.05）. CONCLUSIONS Tofacitinib combined with hydroxychloroquine shows good efficacy and safety for refractory RA.

Exosomes are extracellular vesicles that facilitate cellular communication by transmitting biomolecules and altering the biochemical characteristics of receptor cells. Mesenchymal stem cell-derived exosomes(MSC-Exos)are lipid bilayer vesicles secreted by mesenchymal stem cells(MSCs). These exosomes have similar functions to MSCs and contain bioactive substances such as proteins, lipids, and nucleic acids. MSC-Exos play a vital role in intercellular communication and are involved in essential physiological processes including immune regulation, tissue damage repair, and angiogenesis promotion. Consequently, they have gained significant attention in research, particularly in the treatment of immune inflammatory diseases, ischemic diseases, and other related fields. This article provides an in-depth analysis of the potential treatment mechanisms for dry eye, focusing on the pathogenesis of the condition, including inflammatory reactions, nerve regeneration, and tissue repair. The objective is to establish a foundation for the application of MSC-Exos in the treatment of dry eye, thereby offering a valuable reference for the future clinical applications.

Objective To investigate the expression of serum Maresin 1 and pro-platelet basic protein(PPBP)in patients with diabetes nephropathy(DN)and their correlation with long-term prognosis.Methods A total of 83 patients with diabetes nephropathy admitted to Tangshan Central Hospital from May 2018 to May 2020 were selected as the diabetes nephropathy group.In the same period,60 patients with simple type 2 diabetes were selected as the diabetes group and 60 healthy people as the control group.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of serum Maresin1 and PPBP.Spearman correlation analysis was used to analyze the correlation between the levels of serum Maresin1 and PPBP and renal pathological damage.COX proportional hazard regression analysis was used to analyze the factors influencing the long-term poor prognosis of patients with diabetes nephropathy.ROC curve was used to evaluate the predictive value of serum Maresin1 and PPBP for the long-term poor prognosis.Results The levels of serum Maresin1(15.90±4.53 ng/ml,12.34±4.29 ng/ml,9.65±4.38 ng/ml)in the control group,diabetes group and diabetes nephropathy group were decreased in turn while the levels of serum PPBP(263.45±85.22 pg/ml,349.28±80.49 pg/ml,435.76±87.21 pg/ml)were increased in turn,and the differences were statistically significant(F=35.159,72.678,all P＜0.05).With the increase of IFTA score,interstitial inflammation score,and glomerular grading,serum Maresin1 level was decreased(F=25.838,25.187,9.751,all P＜0.05),while serum PPBP level was increased(F=56.513,92.702,58.137,all P＜0.05),and the differences were statistically significant,respectively.Serum Maresin1 was negatively correlated with IFTA score,interstitial inflammation score,and glomerular grading(r=-0.637,-0.581,-0.594,all P＜0.05),while serum PPBP was positively correlated with IFTA score,interstitial inflammation score,and glomerular grading(r=0.659,0.664,0.608,all P＜0.05),with significant differences.The course of diabetes nephropathy(HR=1.135,95％CI:1.012～1.370),24-hour urinary protein(HR=1.087,95％CI:1.016～1.164),PPBP(HR=1.208,95％CI:1.119～1.365),and IFTA score(HR=1.139,95％CI:1.024～1.219),interstitial inflammation score(HR=1.122,95％CI:1.006～1.249)and glomerular grading(HR=1.139,95％CI:1.052～1.273)were independent risk factors for long-term prognosis of diabetes nephropathy patients,while eGFR(HR=0.934,95％CI:0.892～0.993)and Maresin1(HR=0.903,95％CI:0.816～0.982)were protective factors for long-term prognosis(all P＜0.05).The areas under the curve(AUC)of serum Maresin1,PPBP and two indicators combined to predict the long-term poor prognosis of patients with diabetes nephropathy were 0.781,0.777 and 0.901,respectively.The AUC of two indicators combined was higher than that,and the differences were significant(Z=3.049,3.258,all P＜0.05).Conclusion In patients with diabetes nephropathy,serum Maresin1 was decreased and PPBP was increased,and the two indexes were closely related to the degree of renal injury.The combined test could effectively predict the long-term poor prognosis of patients.

Objective:To prevent postoperative myocardial oedema or other causes of acute heart failure in congenital cardiac disease,anticipating delay sternal closure may reduce the number of children requiring cardiopulmonary resuscitation after surgery.The aim of this study was to describe the rate of delay sternal closure after surgery for congenital cardiac disease and to analyse the risk factors that may be associated with it.Methods:We retrospectively reviewed all surgeries with extracorporeal circulation in the cardiothoracic surgery intensive care unit of Shanghai Children's Medical Center in the past five years,from September 2014 to December 2018.The study cohort was divided into the delay sternal closure group (n=418) and the control group (routine chest closure,n=12 188) according to whether a delay sternal closure was applicated.Risk factors associated with delay sternal closure were identified by multivariate Logistic regression analysis.Results:A total of 12 606 cases were eligible,of which 418 (3.32%) were in the delayed sternal closure group.The most common cardiac diagnosis in the delayed sternal group was transposition of the great arteries (26.8%,112/418),whereas the most common cardiac diagnosis in the control group was ventricular septal defect (45.9%,5 599/12 188).All-cause mortality in children in the delayed sternal closure group was 3.3% (14/418) compared with 0.4% (46/12 188) in the control group,with a statistically significant difference ( P<0.05).Multivariate Logistic regression analysis showed that the need for delayed sternal closure were associated with age ( OR 0.164,95% CI 0.079-0.338, P<0.001),positive intropic support before surgery ( OR 0.42,95% CI 0.252-0.699, P=0.001),sex（ OR 0.742，95% CI 0.648-1.098， P<0.05），mean body weight（ OR 1.192，95% CI 1.078-1.318， P<0.001），positive intropic support before surgery（ OR 0.370，95% CI 0.252-0.699， P<0.001），complicated surgery ( OR 0.241,95% CI 0.159-0.367, P<0.001) and extracorporeal circulation diversion time ( OR 6.412,95% CI 4.339-9.475, P<0.001). Conclusion:Delayed sternal closure is an important management strategy for congenital cardiac surgery in infants and children.Delayed sternal closure is associated with age，sex,mean body weight at the time of surgery,positive intropic support before surgery，complicated surgery and extracorporeal circulation diversion time.