Objective:To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS).Methods:The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis.Results:A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95% CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95% CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR=0.62,95% CI 0.40-0.97 ,P=0.033) and second endpoint ( HR=0.56, 95% CI 0.37-0.87, P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion:On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

Objective:To explore the force distribution on the maxillary dentition when the first and second molars distalized simultaneously with different step sizes using clear aligners in vitro in order to provide a theoretical basis for the rational design of molar distalization. Methods:Clear aligners were designed to simultaneously distalize the maxillary first and second molars bilaterally, with rectangular attachments placed on the buccal surfaces of the first and second premolars, as well as the second molars. Based on different step sizes, the aligners were divided into three groups: Group A (0.15 mm per step), Group B (0.20 mm per step), and Group C (0.25 mm per step). Ten aligners were fabricated for each group using 0.76 mm thick polyethylene terephthalate glycol (PET-G) sheets. A three-dimensional force measurement system was used to measure the forces exerted on each tooth by the aligners, the first and second molars served as the target teeth and the remaining teeth as anchorage teeth. The three-dimensional force data were compared among the three groups.Results:In the mesiodistal direction, the forces on the central and lateral incisors were relatively small among all three groups, with no statistically significant differences ( P>0.05). However, significant differences were observed in the forces on the canines, first premolars, second premolars, first molars, and second molars ( P<0.05). The distal forces on the second molars in Groups B and C were (6.13±1.45) N and (6.83±1.58) N, respectively, significantly higher than that in Group A [(3.51±1.01) N] ( P<0.05). The distal force on the first molars in Group C [(6.62±0.89) N] was significantly higher than that in Groups A and B ( P<0.05). The mesial reactive forces on the first and second premolars in Groups B and C were significantly higher than those in Group A ( P<0.05). The mesial reactive force on the canines in Group C [(-2.98±1.33) N] was significantly higher than that in Group A [(-1.69±0.68) N] ( P<0.05), while there were no significant differences between Groups B and C in the forces on the canines, first premolars, and second premolars ( P>0.05). In the buccolingual direction, there were no statistically significant differences in the forces on the central and lateral incisors among three groups ( P>0.05), but significant differences were observed in the forces on the canines, second premolars, and second molars ( P<0.05). The buccolingual forces on the canines, second premolars, and second molars in Group B were (-0.56±0.54), (-2.07±0.95), (1.13±0.55) N, respectively, significantly higher than those in Group A ( P<0.05), but there were no significant differences compared to Group C ( P>0.05). Compared to the mesiodistal and buccolingual forces, the vertical forces on the target and anchorage teeth were relatively small in all three groups. Conclusions:When using 0.76 mm thick PET-G sheets to fabricate clear aligners for simultaneous molar distalization, a step size of 0.20 mm per step is recommended. To prevent buccal tipping of the molars during distalization, it is advisable to design lingual displacement for the molars and buccal displacement for the adjacent anchorage teeth to counteract the unfavorable forces, with attachments placed on the primary anchorage teeth.

Objective To evaluate the cost-utility of tiotropium/olodaterol in treating Chinese patients with moderate to very severe chronic obstructive pulmonary disease(COPD)and to provide references for selecting more economical inhaled preparations in clinical practice.Methods A four-state lifetime Markov model was established with a 3-month cycle.The health outcomes included life years and quality-adjusted life years.Costs,including direct medical costs,were calculated from the perspective of the Chinese health system.Discontinuation rates were derived from the discontinuation curve using GetData Graph Digitizer.The main output indicator of the model was the incremental cost-utility ratio,which was calculated from the queue simulation results to judge the economy of tiotropium bromide/odataterol.The scenario analysis and sensitivity analyses were carried out to detect the robustness of the base case result.Results Compared with tiotropium bromide,the patient treated with tiotropium bromide/odataterol gained an additional 0.0846 life years,an additional cost of ￥3 201.50,and additional 0.029 6 QALY.The incremental cost-utility ratio was 108 140.11 yuan/QALY,lower than the willingness-to-pay threshold of three times China's per capita GDP in 2021.The costs of tiotropium bromide and tiotropium bromide/odataterol had the greatest impact on the result in the one-way sensitivity analysis.93.8%of the Chinese COPD population was willing to pay for tiotropium bromide/odataterol under the threshold in the probability sensitivity analysis.Conclusion Tiotropium/olodaterol is a cost-effective alternative compared to tiotropium for patients with moderate to very severe COPD in China and the results were robust in the sensitivity analyses.

OBJECTIVE：To c ompare the situation of adverse drug reaction （ADR） collection by social media between European and American countries and China ，so as to provide reference for the improvement of corresponding work in China. METHODS：By retrieving relevant literatures from CNKI ，Web of Science ，Elsevier ScienceDirect ，SpringerLink and so on ， referring to the official website of International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use （ICH），the current situation of ADR collection by social media in European and American countries（organizations）such as the United States ，the European Union ，the United Kingdom ，France was introduced ，and compared with the corresponding work in China. The advantages and possible problems of using social media to collect ADR were analyzed so as to put forward some suggestions on how to use social media to collect ADR in China. RESULTS & CONCLUSIONS：Since 2013，many countries in Europe and the United States have started to collect ADRs using social media （such as Twitter ，Facebook），such as the draft on drug safety issues on social media issued by the Pharmaceutical Research and Manufacturers of America （PhRMA），and the EU organization ’s Innovative Medicines Initiative （IMI）network to identify adverse drug reaction in web media （WEB-RADR）projects. Through this way ，it is more convenient for patients to report ADR ，and helpful for the pharmacovigilance department to collect ADR information in time ，and can be used as an important supplement to the traditional drug safety information report. However ，there are some advantages ，such as mismatch between the health vocabulary spontaneously reported by patients and medical professional vocabulary ，the challenges of balancing the relationship between public health maintenance and patient privacy protection ，and various deviations affecting the reporting rate and quality of ADR collected by social media. When using social media （such as Wechat ，microblog，QQ and other social media or tools ，as well as applications and small programs ）to collect ADR information in China ，it is suggested to ensure the ease of use and security of reporting ADR applications ，and improve the design of applications to comply with E 2B （R3） data elements and information specifications of ICH guidelines for the electronic transmission of individu al security reports. At the same time ，we should give full play to the supervisory role of regulatory department ，consider non-regulatory factors ，and take privacy protection measures to make it conform to ethics.

Objective:To explore the pros and cons of sequential high-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) immediately following early extubated patients with severe respiratory failure (SRF) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so as to provide evidence for clinical selection of optimal scheme.Methods:Consecutive AECOPD patients admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2019 to September 2020 were screened for enrollment. Patients were between 40 years old and 85 years old with acute exacerbation of bronchial-pulmonary infection, who received endotracheal intubation mechanical ventilation (ETI-MV) as the initial respiratory support method. The pattern of synchronous intermittent mandatory ventilation (SIMV) was used in the study. The parameters were set as follows: tidal volume (VT) 8 mL/kg, support pressure 10-15 cmH 2O (1 cmH 2O = 0.098 kPa), positive end-expiratory pressure (PEEP) 4-6 cmH 2O and the ratio of inspiratory to expiratory time 1.5-2.5∶1. Under these conditions, the plateau pressure (Pplat) was maintained less than 30 cmH 2O. The minimum fraction of inspired oxygen was adjusted to keep the pulse oxygen saturation no less than 0.92. When the pulmonary infection control window (PIC window) occurred, the subjects were extubated immediately and randomly divided into two groups, with one group receiving HFNC (called HFNC group), the other group receiving NIPPV (called NIPPV group). Patients with failed sequential HFNC or NIPPV underwent tracheal re-intubation. The rate of tracheal re-intubation within 7 days of extubation, complications (such as nose and face crush injury and gastric distension), in-hospital mortality, duration of ETI before PIC window, length of RICU stay and length of hospital stay were compared, respectively. Results:Forty-four patients were enrolled in the study, 20 in the HFNC group and 24 in the NIPPV group. There was no significant difference in the duration of ETI before PIC window between HFNC and NIPPV groups (hours: 95.9±13.1 vs. 91.8±20.4, P > 0.05). The rate of tracheal re-intubation within 7 days in the HFNC group was significantly higher than that in the NIPPV group [35.0% (7/20) vs. 4.2 % (1/24), P < 0.05]. However, the incidence of complication in the HFNC group was significantly lower than that in the NIPPV group [0% (0/20) vs. 25.0% (6/24), P < 0.05]. Compared with the NIPPV group, the in-hospital mortality in the HFNC group was slightly higher [5.0% (1/20) vs. 4.2% (1/24)], the length of RICU stay (days: 19.5±10.8 vs. 15.5±7.2) and the length of hospital stay (days: 27.4±12.2 vs. 23.3±10.9) were slightly longer, without statistical differences (all P > 0.05). Conclusion:For early extubated patients with SRF due to AECOPD, the compliance of sequential HFNC increased and the complications decreased significantly, but the final effect may be worse than sequential NIPPV.

Nonalcoholic fatty liver disease (NAFLD) has become one of the most prominent causes of chronic liver diseases and malignancies. However, few therapy has been approved. Radix Bupleuri (RB) is the most frequently used herbal medicine for the treatment of liver diseases. In the current study, we aim to systemically evaluate the therapeutic effects of saikosaponin A (SSa) and saikosaponin D (SSd), the major bioactive monomers in RB, against NAFLD and to investigate the underlying mechanisms. Our results demonstrated that both SSa and SSd improved diet-induced NAFLD. Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes, like

Objective: To observe the neuro-protective effect of Levocarnitine on severe hand, foot and mouth disease (HFMD) after enterovirus 71(EV71) infection, to preliminarily explore the possible mechanism preliminarily. Methods: One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Children′s Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases, including 32 males and 34 females, median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levo-carnitine group (66 cases, including 36 males and 30 females, median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females, median age of 2 years and 6 months) who were examined at the Children′s Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100, NSE, soluble apoptosis-related factors (sFas), soluble apoptosis-related factor ligands (sFasL), malondialdehyde (MDA), superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum, efficacy-related indicators such as duration of fever, white blood cell count on the 3^rd day of treatment, time to remission of nervous system symptoms, time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas, sFasL, MDA, SOD and S100, NSE was performed Results: (1) The levels of S100 [(0.38±0.16) μg/L vs. (0.06±0.23) μg/L], NSE [(43.70±8.80) μg/L vs. 10.10±3.60) μg/L], sFas [(6.61±1.86) μg/L vs. (3.88±1.22) μg/L], sFasL[(101.40±20.7) μg/L vs. (54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/L vs. (4.08±1.45) nmol/L] in serum of HFMD group were significantly higher than those of the healthy control group (t=-12.245, -22.895, -8.273, -12.803, -17.960, all P<0.05), while the SOD level [(57.10±10.40) kU/L vs. (70.3±14.4) kU/L] was significantly lower (t=5.457, P<0.05). (2) With the extension of treatment time for HFMD children in the two groups, S100 and NSE in cerebrospinal fluid, S100, NSE, sFas, sFasL and MDA in serum decreased, while SOD level increased.On the 3^rd and 7^th day after treatment, S100 (t₃=3.491, t₇=14.434), NSE (t₃=2.920, t₇=23.490) in cerebrospinal fluid, S100 (t₃=5.277, t₇=3.614), NSE (t₃=4.652, t₇=10.525), sFas (t₃=6.399, t₇=7.514), sFasL (t₃=11.155, t₇=8.804) and MDA (t₃=6.348, t₇=7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P<0.05), while SOD (t₃=3.162, t₇=-3.529) was significantly higher than that of routine group (P<0.05). (3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23±0.65) d vs. (1.84±0.47) d], and WBC on the 3^rd day after treatment [(9.14±2.93)×10⁹/L vs. (7.12±2.58)×10⁹/L] and the progression time of the disease [(29.74±7.85) h vs. (17.36±8.73) h] were significantly better than the those in the routine group (t=-6.178, 4.204, 8.567, all P<0.05). The critical conversion rates of Levocarnitine group and the routine group were 7.58% and 18.18%, respectively, and the difference in critical conversion rate was not statistically significant (χ²=2.316, P>0.05). (4)There was a positive correlation between S100 and sFas, sFasL, MDA in children with HFMD (r=0.373, 0.735, 0.334, P<0.05). NSE was positively correlated with sFas and sFasL (r=0.479, 0.601, all P<0.05), while SOD and S100 were negatively correlated with NSE (r=-0.425, -0.460, all P<0.05). Conclusions Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71, which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.

Objective: To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD). Methods: From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expression<30%) and normal DR group (DR-N, HLA-DR expression>30%) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14⁺ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plasma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score (PCIS) and the pediatric risk of mortality Ⅲ (PRISM Ⅲ) were used to estimate the severity of HFMD. Results: ① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F=47.102, P<0.05). Patients with critical HFMD had the lowest HLA-DR expression (P<0.05). ② The numbers of CD14⁺ monocytes, CD3⁺ T cells, CD4⁺ T cells, CD8⁺ T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in patients with severe or critical HFMD (P<0.05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0.05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0.05). The ratio of IFN-γ/IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0.05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r=-0.704, P<0.05), and positively correlated with the IFN-γ/IL-10 ratio (r=0.773, P<0.05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively correlated with PCIS (r=0.715, P=0.00) and negatively correlated with PRISM Ⅲ (r=-0.610, P=0.00). ⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0.05). Conclusions Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14⁺ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14⁺ monocytes might be associated with severe HFMD and poor prognosis.

Objective To develop and validate a method for detecting factor 8 gene (F8) mutations in hemophilia A patients by Ion Torrent semiconductor sequencing .Methods Intron 22 and intron 1 inversions of F8 gene were identified by long distance PCR (LD-PCR), other mutations in the F8 gene were identified by Ion Torrent sequencing.Candidate variants were validated by Sanger sequencing .Sanger sequencing was applied to screen HA carriers from 11 female family members in the 8 pedigrees.One pregnant woman was offered prenatal diagnosis via analyzing the fetal DNA obtained through amniocentesis . Results Four missense mutations ( c.1331A >C, 1648C >T, c.6506G >A, c.6544C >T), two frameshift mutations ( c.2393 _2394insT, c.6320delG), one splicing mutation ( IVS5 +5G >A), one nonsense mutation (c.43C >T) and one Inv22 mutation were identified in all nine probands respectively . Among 11 female family members, 10 females were identified to be HA carriers, and one didn′t carry the maternal pathogenic mutation.Prenatal diagnosis result showed that the fetus inherited the wild -type maternal allele and was predicted to be unaffected by HA .Conclusion The targeted Ion Torrent sequencing is a reliable and efficient method to detect F8 mutations in patients with Hemophilia A disease .

Objective To research the significance of application of clinical nursing pathway in patients undertaking glossectomy and forearm flap reconstruction.Methods Sixty patients with tongue cancer who undertook glossectomy and forearm flap reconstruction were enrolled.The patients were randomly divided into the experimental group and the control group (30 cases in each group).The patients of the experimental group received nursing following clinical nursing pathway,and the patients in the control group received routine nursing service.The patients and doctors satisfaction evaluation were compared between the two groups with a self-designed nursing quality evaluation form.The qualities of care achieved in 2 groups were compared.Results It took less in-ward time and expenditure in the experimental group compared with the control group.The quality of care,the satisfactory degree of patients and doctors in the exipermental group were significantly higher than those of the control group.Conclusions The establishment and application of the clinical nursing pathway in patients undertaking glossectomy and forearm flap reconstrucition contributes to improve the satisfaction of patients and doctors and the quality of nursing service.