Objective To investigate the clinical efficacy of Modified Yinhuo Guiyuan Huayu Formula(MYGHF)in diabetic retinopathy(DR)patients with yin deficiency and blood stasis syndrome and to observe its regulatory effects on the nuclear factor κB(NF-κB)signaling pathway.Methods A total of 100 DR patients(200 eyes)with yin deficiency and blood stasis syndrome admitted to the Fourth People's Hospital of Hengshui from January 2019 to April 2020 were equally randomized into a control group(50 cases,100 eyes)and an observation group(50 cases,100 eyes)using a random number table.Both groups were required to conduct intensive glycemic control.The control group was treated with conventional western medicine of lecithin-bound iodine,while the observation group received additional MYGHF for 3 months.Parameters of traditional Chinese medicine(TCM)syndrome scores,key components of NF-κB signaling pathway[NF-κB p65,inhibitor of kappa B kinase(IKK),inhibitor kappa B(IκB)],angiogenesis-related factors[fibroblast growth factor 21(FGF21),vascular endothelial growth factor(VEGF),angiopoietin 2(Ang2)],and efficacy indicators[glycated hemoglobin(HbA1c),fasting blood glucose(FBG),homeostasis model assessment of insulin resistance(HOMA-IR),visual field grayscale value,and best-corrected visual acuity(BCVA)]in the two groups were evaluated before treatment and 1 and 3 month(s)after treatment.After treatment,the clinical efficacy and safety of the two groups were assessed.Results(1)After 3 months of treatment,the total effective rate was 88.00%(44/50)in the observation group versus 70.00%(35/50)in the control group,demonstrating significantly superior therapeutic effects of TCM syndrome differentiation in the observation group(tested by chi-square test,P＜0.05).(2)At 1 and 3 month(s)after treatment,both groups showed reduced scores for TCM symptoms of blurred vision,dizziness and tinnitus,soreness and weakness of waist and knees,and feverish sensation in the palms and soles compared to the baseline levels(all P＜0.05).The observation group exhibited significantly greater reductions in these symptom scores than the control group at both time points(all P＜0.05).(3)The protein expression levels of NF-κB p65,IKK were decreased and IκB was increased in both groups at 1 and 3 month(s)after treatment compared to the baseline levels(all P＜0.05),and the observation group demonstrated more pronounced improvement of these key pathway components compared to the control group(all P＜0.05).(4)The levels of angiogenesis-related factors of FGF21,Ang2,and VEGF were significantly reduced in both groups at 1 and 3 month(s)compared to the baseline levels(all P＜0.05),and the observation group showed superior decreases compared to the control group(all P＜0.05).(5)The efficacy indicators of HbA1c,FBG,HOMA-IR,visual field grayscale values,and BCVA were improved in both groups at post-treatment 1 and 3 month(s)compared to the baseline levels(all P＜0.05),and the observation group achieved significantly superior improvement in all indicators compared to the control group(all P＜0.05).(6)The total incidence of adverse reactions was 2.00%(1/50)in the observation group versus 8.00%(4/50)in the control group,with no statistically significant difference between groups(P＞0.05).Conclusion MYGHF effectively alleviates clinical symptoms in patients with DR of yin deficiency and blood stasis type,and is effective on modulating angiogenesis-related factors and suppressing NF-κB signaling pathway activation,demonstrating satisfactory efficacy and good safety profile.

This paper summarized the clinical experience of using the method of “returning fire to its origin” for treatment of paroxysmal sympathetic hyperactivity （PSH）. According to the causes and clinical characteristics of PSH， the author believes that the deficiency of kidney qi， and the loss of yin and yang are the basis of the pathogenesis of PSH. Fright causes qi to be chaotic as the triggering mechanism of PSH. The key mechanism of PSH is that the deficiency yang with upper manifestation， and the fire does not return to its origin. The treatment should be nourishing yin and astringing yang， by taking modified Yinhuo Decoction （引火汤） internally， and receiving warm moxibustion as the first choice externally with selected acupoints Guanyuan （CV 4）， Mingmen （GV 4）， and bilateral Yongquan （KI 1）； For prevention， attention should be paid to take care of stomach qi， support healthy qi， and cultivate original qi.

Objective:To explore any effect of regular aerobic exercise on liver fibrosis in rats with non-alcoholic fatty liver disease (NAFLD) and its mechanism.Methods:Twenty-four 8-week-old male OLETF rats were randomly divided into a model sedentary group and a model exercise group, each of 12. Twelve age- and sex-matched LETO rats of the same strain were selected into the healthy control group. The model exercise group underwent treadmill exercise training for 12 weeks, while the other two groups undertook no exercise. After the training, fasting blood glucose, insulin and glycosylated hemoglobin (HbA1c) were measured using colorimetry. Liver tissue was resected to observe any histopathological changes using Masson staining and to measure the collagen volume fraction. Zymography was applied to determine the activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the liver. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), α-smooth muscle actin (αSMA), cysteine-rich protein 61 (CCN1), transforming growth factor-β (TGF-β), MMP-12 and the tissue inhibitor of metalloproteinase-1 (TIMP-1) proteins in the liver were quantified using western blotting.Results:Compared with the healthy control group, the model sedentary group on average displayed a significant increase in body weight, fasting blood glucose, fasting insulin, HbA1c, liver collagen volume fraction, and the protein expression of TGF-β, αSMA, CCN1, IL-1β, TNF-α, and MMP-12. There was a significant decrease in the activity of MMP-2 and MMP-9 on average. Compared with the model sedentary group, the model exercise group on average displayed lower fasting blood glucose, fasting insulin, HbA1c, and liver collagen volume fraction, as well as less expression of TGF-β, αSMA, IL-1β, TNF-α, and MMP-12 protein. MMP-2 and MMP-9 activity was higher, as was the expression of CCN1 protein. There were no significant differences in average body weight between the model sedentary and exercise groups.Conclusion:Regular exercise can delay liver fibrosis, at least in NAFLD rats. The mechanism is related to inhibiting hepatic inflammatory response, the activation of hepatic stellate cells and improving extracellular matrix remodeling.

The management of surplus drugs is an important part of drug administration. At present, China′s medical institutions are in the initial exploration stage in managing surplus drugs.This study analyzed the causes, safety hazards, management policies, and management problems of surplus drugs in medical institutions, and proposed targeted countermeasures and suggestions, including establishing unified and standardized management methods, consensus or guidelines, optimizing internal management of medical institutions, improving the management awareness of medical staff, and clarifying the benefits of surplus drugs, so as to provide references for medical institutions to manage surplus drugs reasonably.

To standardize the management of surplus drugs, improve the efficiency of medical resource utilization, promote the rational use of medical insurance funds, and reduce the financial burden on patients, a large tertiary hospital implemented a practice for managing surplus drugs starting in May 2023. This practice encompassed multiple aspects, including the establishment of organizational structure, clarification of responsibilities, formulation of billing for fractional doses and a reasonable surplus drugs list, establishment of standardized management processes, and allocation of special funds for surplus drugs. These efforts had initially achieved effective management of surplus drugs. As of November 2023, the management of surplus drugs had benefited 136 908 patients, with an average savings of 873.61 yuan per patient and a cumulative savings of approximately 34.7 million yuan in medical insurance funds. This practice had effectively reduced the wastage of medical resources, and could provide references for promoting standardized management of surplus drugs in medical institutions of China. In the future, the hospital should further expand the coverage of surplus drugs, ensure patients′ rights to informed consent, and establish a comprehensive performance incentive mechanism to promote the sustainable development of surplus drug management.

Objective To study the prognostic factors of progressive hearing loss among children with large vestibular aqueduct syndrome(LVAS).Methods The clinical data of 49 children(95 ears)with LVAS who re-ceived at least two hearing tests from January 2017 to January 2023 in our hospital were retrospectively analyzed,and they were divided into two groups according to the progression of hearing loss:the stable group(55 ears)and the progressive group(40 ears).The effects for progressive hearing loss of initial age,gender,laterality,imaging features,audiometric data,and incomplete partition type Ⅱ(IP-Ⅱ)and SLC26A4(type A,B,C,D)genotypes were analyzed by univariate and multivariate Cox regression analysis.The potential prognostic factors were further verified by Kaplan-Meier survival analysis.Results Each dB decrease in the initial average hearing threshold in-creased the expected hazard by 7.03％(P=0.02).Incomplete partition type Ⅱ(IP-Ⅱ)was associated with 5.11 hazard ratio(95％CI,1.81 to 14.45,P=0.002).Genotype C was associated with 6.13 hazard ratio for progressive hearing loss(95％CI,2.07 to 18.13,P=0.001).Conclusion The initial average hearing threshold,IP-Ⅱ,and SLC26A4 genotype C were significant effect factors of progressive hearing loss in patients with LVAS.This could predict the progression of hearing loss in children with LVAS and help identify patients at high risk for progressive hearing loss.

Objective:To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients.Methods:In the follow-up cohort of patients with newly diagnosed MM and who received “novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy” in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results:The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions:The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

Objective:To observe any effect of regular aerobic exercise on cardiac remodeling in spontaneously hypertensive rats (SHR) and explore the mechanism of endothelial nitric oxide synthase (eNOS) uncoupling.Methods:Thirty 6-week-old healthy male SHR were divided into a sedentary group and an exercise group, each of 15. Another ten age- and sex-matched Wistar-Kyoto rats were set as a normal control group. The animals in the normal control and sedentary groups were fed quietly in their cages, and those in the exercise group performed moderate intensity treadmill exercise for 8 weeks (5 times per week). Forty-eight hours after the last training, echocardiography was applied to document cardiac structure and function in both groups. Wheat germ agglutinin staining and Picrosirius Red staining were used to obtain the cardiomyocyte cross sectional areas (CSAs) and interstitial collagen volume fractions (CVFs) of all of the mice. The rates of cardiomyocyte apoptosis were measured using TUNEL staining, and myocardial tetrahydrobiopterin (BH4) content was measured using high-performance liquid chromatography. Total eNOS, eNOS dimer and eNOS monomer protein expression in the myocardia were detected using western blotting.Results:Compared with the normal control group, the left ventricular wall thickness (LVWT), myocardial CSA, CVF, apoptosis of cardiomyocytes and eNOS monomer levels were significantly higher in the sedentary group, on average. But the end-diastolic diameter (LVEDD) and ejection fraction (LVEF) of the left ventricle and the levels of eNOS dimer and myocardial BH4 and the eNOS dimer/monomer ratio tended to be lower. Comparing the exercise group with the sedentary group, the average LVEDD, LVEF, eNOS dimer, eNOS dimer/monomer ratio and myocardial BH4 content were significantly higher in the exercise group, but the myocardial CVF, cardiomyocyte apoptosis and eNOS monomer levels were significantly lower. LVWT and CSA were not significantly different. There were no significant differences in the total eNOS protein levels among the three groups.Conclusion:Regular aerobic exercise might improve cardiac remodeling in cases of spontaneous hypertension regulating eNOS uncoupling, at least in rats.

Objective: To understand the current status of main professional work in independent school health departments of Chinese centers for disease control and prevention, so as to provide reference and suggestions for the further development of school health work in China. Methods: Electronic questionnaire was used to collect the basic work of school health, the monitoring work, the intervention action of common diseases and the development of health intervention among students in independent school health departments of centers for disease control and prevention in China. Results: Among the 357 institutions that have set up independent school health departments, the implementation rates of school mental health work, safety emergency and risk avoidance health intervention were low, which were 11.8% and 11.5%, respectively. Relying on the project "national monitoring and intervention of common diseases and health influencing factors of students", the overall implementation of health monitoring in schools nationwide was successful, but the overall implementation rate of students nutritional status monitoring and "healthy parents action" were low, accounting for 44.5% and 24.4%, respectively. At the same time, there were still as many as 27.2% institutions that had not carried out the intervention action for common diseases of students which advocated in the monitoring program. The failure rate of county level institutions was higher than that of provincial level and prefecture level institutions, and the failure rate of the central and western institutions was much higher than that of the eastern institutions; the difference was statistically significant( χ 2=30.1, 41.6, P <0.05). Conclusion We should increase support including policy preference, fund guarantee, technical guidance and so on for the school health work of disease control institutions at the grass roots level and in economically underdeveloped areas, so as to ensure the healthy growth of children and adolescents in all respects.

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome