ObjectiveTo investigate the possible mechanism of action of Xibining Formula （膝痹宁） for cartilage damage in knee osteoarthritis （KOA） through the cyclic guanosine-adenosine monophosphate synthase （cGAS）- stimulator of interferon genes （STING） signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups （10 per group）， sham operation group， KOA model group， low-dose Xibining Formula group， high-dose Xibining Formula group， and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus （DMM） method in all groups but the sham surgery group. Two weeks after surgery， the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/（kg·d） and 14.32 g/（kg·d） respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/（kg·d） of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan （DMXAA） at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/（kg·d） via gavage， once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were measured by ELISA； pathological changes in cartilage tissue were observed using hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system； the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 （MMP3）， matrix metalloproteinase 13 （MMP13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS）， type-Ⅱ collagen （CⅡ） and aggregated proteoglycan （Aggrecan）， and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group， the KOA model group showed severe cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with the control group， serum level of IL-6， IL-1β， TNF-α in all the intervented groups decreased （P＜0.01）， while compared with high-dose Xibining Formula group， level of IL-6， IL-1β， and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased （P＜0.01）. Compared with the KOA model group， all the intervention groups exhibited alleviated cartilage pathological changes， signi-ficantly reduced Mankin scores， significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly decreased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with high-dose Xibining Formula group， high-dose Xibining Formula + agonist group showed cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway， decreasing matrix degradation-related proteins， and elevating matrix composition-related proteins.

Objective To explore the potential causal relationship between occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") and five mental disorders (depression, bipolar disorder, schizophrenia, insomnia and anxiety) using the two-sample Mendelian randomization (MR) method. Methods Single nucleotide polymorphisms (SNPs) loci associated with pneumoconiosis and five mental disorders were screened from Genome-Wide Association Studies. Inverse variance weighting (IVW), weighted median (WM) and MR-Egger regression methods were used to evaluate the significance of the causal relationship between pneumoconiosis and five mental disorders. Sensitivity analysis was used to evaluate the accuracy and reliability of the research results. Results After matching data of pneumoconiosis and the five mental disorders, 16 SNPs were ultimately included as instrumental variables in this study. The result of MR analysis revealed a positive causal relationship between pneumoconiosis and both depression [IVW: odds ratio (OR) and 95% confidence interval (CI) was 1.017 (1.000-1.035), P<0.05] and bipolar disorder [IVW: OR(95%CI)was 1.046(1.009-1.083), P<0.05; WM: OR (95%CI) was 1.055(1.007-1.105), P<0.05]. Result of sensitivity analysis indicated there was no heterogeneity and horizontal pleiotropy in the above results. There was no causal association observed between pneumoconiosis and schizophrenia, insomnia, or anxiety disorders (all P>0.05). Conclusion This study provides genetic evidence supporting a positive causal relationship between pneumoconiosis and both depression and bipolar disorder.

Objective:To discuss and analyze the current situation of the application and approval of new Chinese medicine in China; To provide a reference for the research and development of new Chinese medicines in the future.Methods:The drug registration data were retrieved from Xanda database from January 1, 2016 to December 31, 2022, and the information of new approval and application of new Chinese medicines during this periods was systematically organized from the aspects of the number of registered varieties, registration categories, therapeutic areas, prescription sources, dosage form distribution, development cycle, clinical research and control drugs.Results:From 2016 to 2022, the total number of application for new Chinese medicines was 265. The number of registration classification 1.1 of new compound drugs was the largest. The dosage forms of new drugs were mainly granules, capsules, and tablets. Indications mainly focused on respiratory, neuropsychiatric, digestion and cardio-cerebrovascular diseases, etc. From 2016 to 2022, the total number of approval for new Chinese medicines was 29, of these, 19 from 2021 to 2022. The number of registration classification 1.1 of new Chinese medicines was the largest. The treatment fields are mainly respiratory system, gynecology and neuropsychiatric diseases, etc. The dosage forms of new drugs were mainly granules, capsules, and tablets. The number of drugs in prescriptions was 6-15. High-frequency drugs included Glycyrrhizae Radix et Rhizoma, Ephedrae Herba, Scutellariae Radix, Pinelliae Rhizoma, Poria and Gypsum Fibrosum. Phase Ⅱ and phase Ⅲ of the clinical trials had the largest number. The development period was approximately between 10-20 years. The most prescription source of new drugs was clinical experienced prescriptions and hospital pharmaceutics.Conclusion:The results show that China has been gradually building-up a relatively complete ecosystem for research and development of new Chinese medicines, helping to develop more high-quality Chinese medicines.

A non-invasive deep learning method is proposed for reconstructing arterial blood pressure signals from photoplethysmography signals.The method employs U-Net as a feature extractor,and a module referred to as bidirectional temporal processor is designed to extract time-dependent information on an individual model basis.The bidirectional temporal processor module utilizes a BiLSTM network to effectively analyze time series data in both forward and backward directions.Furthermore,a deep supervision approach which involves training the model to focus on various aspects of data features is adopted to enhance the accuracy of the predicted waveforms.The differences between actual and predicted values are 2.89±2.43,1.55±1.79 and 1.52±1.47 mmHg on systolic blood pressure,diastolic blood pressure and mean arterial pressure,respectively,suggesting the superiority of the proposed method over the existing techniques,and demonstrating its application potential.

OBJECTIVE：To study the mecha nism of Bambuterol hydrochloride in the improvement of chronic obstructive pulmonary disease （COPD）model rats ，and to find the potential biomarker. METHODS ：Totally 30 rats were randomly divided into normal group ，model group and bambuterol hydrochloride group （3.3 mg/kg），with 10 rats in each group ；COPD model was established by lipopolysaccharide （LPS）infusion combined with smoking in model group and bambuterol hydrochloride group. After modeling ，bambuterol hydrochloride group was given relevant medicine intragastrically ，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 45 d. After last medication ，the serum sample and alveolar lavage fluid of rats were collected. The levels of interleukin- 6（IL-6）and tumor necrosis factor-α（TNF-α）in alveolar lavage fluid were detected by ELISA. The serum metabolites were detected by LC-MS and analyzed by metabolomics. Orthogonal partial least squares discriminant analysis （OPLS-DA）was used to screen out the differential metabolites. The potential biomarkers were identified based on the related literature ，and the metabolic pathway enrichment analysis was carried out by MetPA analysis platform. RESULTS ：Compared with normal group ，the levels of IL- 6 and TNF-α in alveolar lavage fluid of rats were increased significantly in model group （P＜0.05）. Compared with model group ，the levels of IL- 6 and TNF-α in alveolar lavage fluid of rats were decreased significantly in bambuterol hydrochloride group （P＜0.05）. Results of metabolomics and OPLS-DA showed that 21 differential metabolites and 12 potential biomarkers were found （including maleylpyruvate ， hydroxypyruvate， tartronate semialdehyde，etc.）. Bambuterol hydrochloride can significantly reduce the levels of maleylpyruvate ，methylselenocysteine and 5-deoxy-D-glucuronic acid （P＜0.05）， while increase the levels of hydroxypyruvate ， tartronate semialdehyde and. These biomarkers were mainly @163.com concentrated in pentose phosphoric acid pathway ，glyoxyli acid and tricarboxylic acid metabolism pathway ，followed by 开发。E-mail：pn333@163.com inositol phosphoric acid metabolism pathway ，arginine and tyrosine metabolism pathway ，glycine，serine and threonine metabolism pathway. CONCLUSIONS ：The mechanism of bambuterol hydrochloride improving COPD may be associated with the decrease of the levels of TNF-α and IL-6，as well as the pathway of amino acid metabolism ，energy metabolism and lipid metabolism.

Objective: To effectively reduce the concentration of poisons in cleanroom, protect the health of workers, realize the optimization and automatic control of the new return air device. And the influence of initial concentration, air volume, temperature and relative humidity of formaldehyde on the purification effect of the new return air device was explored. Methods: The purification effect of the new return air device installed with the activated carbon and the photocatalyst purification net or ordinary activated carbon purification network was tested in a 60 m³ simulated cleanroom. The concentration of formaldehyde was determined by solution absorption-phenol reagent spectrophotometry. Based on the single factor experiment to determine the combination of two purification nets. The effects of air volume, initial formaldehyde concentration, temperature and relative humidity on the purification effect of the new return air device were investigated by orthogonal test. Then, the performance parameters of the return air device to purify formaldehyde were determined. Results: The formaldehyde purification efficiency of the two types of purification nets in the new return air device was higher than that of the ordinary activated carbon purification network (P<0.05) . The combination of activated carbon and photocatalyst purification net has no effect on the formaldehyde purification efficiency of the return air device (P>0.05) . According to the direct analysis and variance analysis, air volume was the most sensitive factor (F value is 18.894, P<0.05) , followed by initial concentration (F value is 16.128, P<0.05) , while temperature and relative humidity have little effect (F value is 0.041 and 0.599, respectively, P>0.05) . LSD analysis showed that there was no significant difference in the purification efficiency of formaldehyde between 475 m³/h and 626 m³/h (P>0.05) . From the perspective of formaldehyde purification efficiency and energy saving, when the air volume is set to 475 m³/h, the new return air device has higher purification efficiency for high concentration of formaldehyde. Conclusion The new return air device consisting of activated carbon and photocatalyst purification net can play a good purification role in cleanroom with different temperatures and different humidity. Its formaldehyde purification efficiency is affected by air volume and initial concentration.

Objective To observe the clinical effects of breaking blood expelling stasis method of traditional Chinese medicine (TCM) combined with edaravone on patients with acute hypertensive intra-cerebral hemorrhage and preliminarily discuss its protection mechanism on this disease. Methods Ninety-two patients with hypertensive intra-cerebral hemorrhage within 72 hours after occurrence admitted to Zengcheng District People's Hosipital of Guangzhou from May 2013 to December 2017 were enrolled, they were divided into conventional therapy group and combined treatment of TCM and western medicine group by random numbers produced by a computer, 46 cases in each group. The conventional therapy group was treated with conventional therapy, and the combined treatment of TCM and western medicine group was treated with conventional therapy, additionally the treatment of Poxue Zhuyu decoction (the ingredients of the decoction: leech 10 g, gradfly 10 g, rhubarb 15 g, cattail pollen 5 g, trichosanthes fruit 10 g, radix notoginseng 5 g, colla plastri testudinis 10 g, grassleaf sweetflag rhizome 10 g, ground beetle 3 g, dried lacquer 3 g, peach seed 10 g) and edaravone for 10 days. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were tested by enzyme-linked immunosorbent assay (ELISA) before and 7 days after treatment in the two groups; and the differences in National Institutes of Health stroke scale score (NIHSS) before and 14 days, 90 days after treatment as well as the changes of brain edema around the hematoma 14 days after treatment were compared between the two groups, and the incidence of adverse reaction was observed. Results After treatment, the levels of TNF-α, IL-6 and intra-cerebral hemorrhage quantities in the two groups were all decreased compared with those before treatment, and the degrees of decrease of TNF-α and cerebral hemorrhage volume in combined treatment of TCM and western medicine group were more significant than those in the conventional treatment group [TNF-α (ng/L): 21.00±6.10 vs. 29.40±11.33, cerebral hemorrhage volume (mL): 5.23±0.60 vs. 8.50±0.64, both P <0.05]. The IL-6 in the two groups were recovered to approximately normal levels after the treatment (ng/L: 13.60±5.36 vs. 15.40±6.13, P > 0.05). With the prolongation of therapeutic time, the scores of NIHSS of the two groups were significantly lowered than those before treatment, and the degree of reduction in the combined TCM and western medicine group on 90 days after treatment was more obvious than that of the conventional treatment group (4.34±0.67 vs. 7.73±0.61, P < 0.05). The volumes of edema around hematomas were increased after treatment in the two groups, but the degree of increase in combined treatment of TCM and western medicine group was slower than that of the conventional group (cm3: 7.57±0.64 vs. 10.16±0.60, P < 0.05). There was no statistical significant difference in the incidence of adverse reactions in comparison between the combined treatment of TCM and western medicine group and conventional therapy group [18.2% (8/44) vs. 20.5% (9/44), P > 0.05]. Conclusions Using breaking blood expelling stasis and edaravone for treatment of acute hypertensive intra-cerebral hemorrhage can accelerate the absorption of brain hematoma and improve the neurological function, and its mechanism may be relevant to the inhibition of some inflammatory factors.

Objective To evaluate the clinical effect of dextromethorphan and its effect on daily living of patients with poststroke pseudobulbar affect. Methods Sixty patients with poststroke pseudobulbar affect admitted in our hospital from May 2013 to October 2016 were enrolled. Then they were randomly divided into the control group and the treatment group,with 30 patients in each group.Patients in the control group were treated with fluox-etine therapy and patients in the treatment group were treated with dextromethorphan therapy.The center for neuro-logic study lability scale(CNS-LS)and activity of daily living(Barthel index,BI)before and 30 days after the treat-ments in the two groups had been accessed. Results Thirty days after the treatment,CNS-LS of the treatment group had obvious improvement compared with that before treatment(P < 0.01),but CNS-LS of the control group had no obvious improvement compared with that before treatment(P > 0.05). And significant improvement has been found 30 days after the treatment between the two groups(P<0.01).Furthermore,significant difference was found on BI between these two groups(P<0.05).Conclusions Dextromethorphan is effective in treatment of pa-tients with poststroke pseudobulbar affect and it can improve the activity of daily living of these patients.

Objective To investigate the status quo of illness uncertainty and role adaptation in mothers with babies in Neonatal Intensive Care Unit (NICU) and to explore the correlation between the two. Methods Totally 300 mothers with babies admitted in the NICU of 3 Class Ⅲ Grade A hospitals in Wenzhou between April and November 2017 were selected by convenient sampling. The demographic characteristics questionnaire for parents with babies in NICU, the Mishel Illness Uncertainty Scale for Parents and the Role Adaptation Questionnaire were used to investigate the mothers. The univariate analysis, Pearson correlation analysis and multiple stepwise regression analysis were employed to explore the influencing factors to their role adaptation. A total of 300 questionnaires were distributed, and 273 valid questionnaires were collected. Results The total score of the Mischel Illness Uncertainty Scale in the 273 mothers with babies in NICU was (98.58±11.78), and their score in role adaptation was (59.84±8.16). Illness uncertainty and role adaptation were negatively correlated in the mothers with babies in NICU (r=-0.230, P＜0.05). According to the multiple stepwise regression analysis, complexity and information famine in illness uncertainty of mothers were the influencing factors to the mothers' role adaptation. Conclusions The level of role adaptation in mothers with babies in NICU is low, and their illness uncertainty may be used to predict their role adaptation. NICU nursing staff should take targeted measures to reduce the mothers' illness uncertainty and improve their role adaptation.

OBJECTIVE:To provide reference for the realization of normalization and standardization of quality control and management of Pharmacy intravenous admixture service(PIVAS). METHODS:The management and effectiveness of PIVAS quali-ty control in our hospital were introduced from aspects of the establishment of internal quality control system,the key indicators and effects of quality control. RESULTS:According to checking items from aspects of examining once in a month,on prescription checking,preparation,infection control,equipments,drugs,consumable materials,sanitation;holding 1 monthly quality control reviews;and analyzing unqualified indexes and existing security risks,the quality control of PIVAS had achieved good results. The qualified percentage of quality control index was increased from 84%(Jan. 2016)to 90%(Jun. 2016),error rate in the same peri-od was decreased from 0.579‰ to 0.099‰. CONCLUSIONS:Developing quality control of the implementation of detailed quality control key indexes for the whole process of intravenous infusion in PIVAS can effectively regulate the position working process,re-duce preparation error and ensure the quality of infusion preparation.