Objective To investigate the mechanisms of 6-hydroxygenistein(6-OHG)in the treatment of high-altitude hypoxia-induced lung injury.Methods The intersection targets of 6-OHG and high-altitude hypoxia-induced lung injury were identified using databases,including Swiss Target Prediction,SuperPred,GeneCards,and OMIM.The STRING database and Cytoscape software were used to construct a protein interaction network for the intersection targets of drugs and diseases,and targets with degree values greater than the median were identified as key targets.GO and KEGG enrichment analyses of key targets were performed using the DAVID database to identify relevant signaling pathways.The Maestro 13.7 software was used for molecular docking validation.A large hypobaric hypoxic chamber was used to establish a high-altitude lung injury model in mice.A total of 42 male BALB/c mice were randomly assigned to 3 groups(n=14 in each group),including a normal control group,which was exposed to the environmental conditions at the altitude of 1400 m and received a single intraperitoneal injection of normal saline,a model group,which received a single intraperitoneal injection of normal saline,and a 6-OHG group,which received a single intraperitoneal injection of 6-OHG at 100 mg/kg.Then,1 h after drug administration,mice in the model and 6-OHG groups were placed in a large hypobaric hypoxic simulation chamber for animal experiments.Then,they ascended to an altitude of 8 000 m at a speed of 10 m/s,remained in that environment for 24 h,and then descended to an altitude of 3500 m.Mice in the three groups were sacrificed,and their lung tissues were extracted to measure the water content in the lungs.Pathological changes were observed using HE staining,and the levels of malondialdehyde(MDA),H2O2,total superoxide dismutase(T-SOD),and glutathione(GSH)were measured.Western blot was performed to determine the expression levles of p-PI3K/PI3K,p-AKT/AKT,hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF)proteins.Results Key targets such as serine/threonine protein kinase 1(AKT1),HIF-1α,epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9),and peroxisome proliferator-activated receptor A(PPARA)were identified.GO and KEGG enrichment analyses showed that the targets of 6-OHG in the treatment of high altitude hypoxia-induced lung injury were mainly involved in PI3K/AKT,HIF-1α/VEGF,tumor necrosis factor(TNF),and other signaling pathways.The results of animal experiments demonstrated that compared with the model group,the 6-OHG group showed significant improvement in the pathological damage of lung tissues induced by high altitude hypoxia,presenting statistically significant differences in the levels of MDA,H2O2,GSH,and T-SOD(P＜0.01).The results of Western blot assay revealed statistically significant differences in the p-PI3K/PI3K,p-AKT/AKT,HIF-1α,and VEGF levels in the lung tissues of the 6-OHG group compared with those of the model group(P＜0.01).The molecular docking results showed that 6-OHG could form stable binding with PI3K,AKT,HIF-1α,and VEGF.Conclusion 6-OHG may alleviate lung injury induced by high altitude hypoxia in mice by activating the PI3K/AKT signaling pathway and inhibiting the HIF/VEGF signaling pathway.

This paper discussed the clinical ideas and methods of treating diabetes by improving symptoms. Diabetes-related symptoms can affect the control of blood glucose and other metabolic indicators to varying degrees， and affect the quality of life of patients. In the clinical diagnosis and treatment of diabetes， “equal emphasis on both indicators” is suggested， meaning that quality of life indicators is as important as metabolic indicators. The patient's symptoms should be paied attention to， and the diagnosis and treatment should start from “symptom differentiation”， and emphasize the “key symptoms”. When there are many symptoms， it is advised to adopt the combined treatment mode of “syndrome cluster”， and take the principle of “treating both the root and accompanying symptoms in mild cases with multiple symptoms， and prescribing multiple formulas daily”. At the same time， the model of co-management of three disciplines of diabetes consisting of diabetes specialists， traditional Chinese medicine doctors， and health managers can help the management of diabetes symptoms.

Objective:To construct a predictive model to assess the risk of severe respiratory syncytial virus infection among children under five years in China, conduct preliminary validation of this model by using external data, and develop an individual risk assessment tool available for their parents.Methods:The admission after RSV infection was used as a marker of severe infection. Based on the evidence of RSV hospitalization-related risk factors and real-world data, such as the prevalence of various risk factors in children under five years old in China, a Monte Carlo-based individual RSV hospitalization risk prediction model for children under five years old was constructed. Taking Suzhou City as an example, the model was externally validated, and an interactive risk prediction tool (RSV HeaRT) was developed on the WeChat mini-program platform.Results:The estimation model showed that in children under five years old in China if the population did not have any risk factors for severe RSV infection, the RSV annual hospitalization rate was 2.2/1 000 (95% CI: 0.9/1 000-7.5/1 000). Based on this baseline hospitalization rate and the prevalence of related risk factors in Suzhou, the model predicted an RSV hospitalization rate of 8.0/1 000 (95% CI: 4.6/1 000-24.4/1 000) for children under five years old annually in Suzhou, which was close to the reported RSV hospitalization rate in literature (10/1 000-20/1 000). In the developed RSV HeaRT WeChat mini-program, target users (such as parents of children) could input basic information, disease history, and social environmental factors of the child into the mini-program, and the tool could provide real-time feedback on the following predicted results: First, the relative risk of hospitalization due to RSV infection in current children compared to general children; Second, the probability of hospitalization due to RSV infection within the next year; Third, the relative risk of adverse outcomes during hospitalization in the event of RSV infection. Conclusion:This study is based on real-world evidence related to RSV hospitalization risk and constructs an RSV hospitalization risk prediction model suitable for Chinese children based on the combination of the current prevalence of risk factors in children under five years old in China. The accuracy of the prediction model results has been preliminarily demonstrated. Based on this design, the RSV HeaRT developed can facilitate parents to evaluate the hospitalization risk of children.

Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P＜0.01).Insomnia was reported by 37.0％of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00％±2.38％vs.8.26％±1.73％,P＜0.01).Gastrointestinal symptoms were present in 57.5％of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26％±2.23％vs.8.43％±1.98％,P＜0.01).Furthermore,26.3％of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18％±2.44％vs.8.45％±1.86％,P＜0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P＜0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5％(P＜0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.

Objective:To construct a predictive model to assess the risk of severe respiratory syncytial virus infection among children under five years in China, conduct preliminary validation of this model by using external data, and develop an individual risk assessment tool available for their parents.Methods:The admission after RSV infection was used as a marker of severe infection. Based on the evidence of RSV hospitalization-related risk factors and real-world data, such as the prevalence of various risk factors in children under five years old in China, a Monte Carlo-based individual RSV hospitalization risk prediction model for children under five years old was constructed. Taking Suzhou City as an example, the model was externally validated, and an interactive risk prediction tool (RSV HeaRT) was developed on the WeChat mini-program platform.Results:The estimation model showed that in children under five years old in China if the population did not have any risk factors for severe RSV infection, the RSV annual hospitalization rate was 2.2/1 000 (95% CI: 0.9/1 000-7.5/1 000). Based on this baseline hospitalization rate and the prevalence of related risk factors in Suzhou, the model predicted an RSV hospitalization rate of 8.0/1 000 (95% CI: 4.6/1 000-24.4/1 000) for children under five years old annually in Suzhou, which was close to the reported RSV hospitalization rate in literature (10/1 000-20/1 000). In the developed RSV HeaRT WeChat mini-program, target users (such as parents of children) could input basic information, disease history, and social environmental factors of the child into the mini-program, and the tool could provide real-time feedback on the following predicted results: First, the relative risk of hospitalization due to RSV infection in current children compared to general children; Second, the probability of hospitalization due to RSV infection within the next year; Third, the relative risk of adverse outcomes during hospitalization in the event of RSV infection. Conclusion:This study is based on real-world evidence related to RSV hospitalization risk and constructs an RSV hospitalization risk prediction model suitable for Chinese children based on the combination of the current prevalence of risk factors in children under five years old in China. The accuracy of the prediction model results has been preliminarily demonstrated. Based on this design, the RSV HeaRT developed can facilitate parents to evaluate the hospitalization risk of children.

Objective:To analyze the accuracy of lung ultrasound and chest X-ray in the diagnosis of neonatal pulmonary disease.Methods:We prospectively collected newborns that needed chest X-ray examination to diagnose pulmonary disease from twelve neonatal intensive care units across the country between June 2019 and April 2020.Each newborn was examined by lung ultrasound within two hours after chest X-ray examination.All chest X-ray and lung ultrasound images were independently read by a radiologist and a sonographer.When there was a disagreement, a panel of two experienced physicians made a final diagnosis based on the clinical history, chest X-ray and lung ultrasound images.Results:A total of 1 100 newborns were enrolled in our study.The diagnostic agreement between chest X-ray and lung ultrasound(Cohen′s kappa coefficient=0.347) was fair.Lung ultrasound(area under the curve=0.778; 95% CI 0.753-0.803) performed significantly better than chest X-ray(area under the curve=0.513; 95% CI 0.483-0.543) in the diagnosis of transient tachypnea of the newborn( P<0.001). The accuracy of lung ultrasound in diagnosing neonatal respiratory distress syndrome, meconium aspiration syndrome, pneumonia and neonatal pulmonary atelectasis was similar to that of chest X-ray. Conclusion:Lung ultrasound, as a low-cost, simple and radiation-free auxiliary examination method, has a diagnostic accuracy close to or even better than that of chest X-ray, which may replace chest X-ray in the diagnosis of some neonatal lung diseases.It should be noted that both chest X-ray and lung ultrasound can only be used as auxiliary means for the diagnosis of lung diseases, and it is necessary to combine imaging with the clinical history and presentation.

Objective:To investigate the influence of hemoglobin glycation index (HGI) on the risk of incident chronic kidney disease (CDK) among nondiabetic patients.Methods:Prospective cohort study. At baseline, a total of 7 407 nondiabetic patients without a history of CKD from Pingguoyuan Community of the Shijingshan District in Beijing were included from December 2011 to August 2012, who were then divided into three groups according to the tertiles of their baseline HGI levels. The CKD incidence rate was compared among the different HGI groups at last follow-up. Cox multivariable regression was applied to evaluate whether HGI measures predicted CKD risk. Test for trend across tertiles were examined using ordinal values in separate models.Results:The mean age of the subjects was (56.4±7.5) years, and 4 933 (66.6%) were female. At mean follow-up of 3.23 years, 107 (1.4%) individuals developed CKD. The incidence of CKD was gradually increasing from the low to high HGI groups [1.1% (28/2 473) vs. 1.2% (31/2 564) vs. 2.0% (48/2 370), P=0.016]. In the multivariate Cox regression analysis, after adjustment for potential confounders, the high HGI group had a 68.5% increased risk of CKD compared with the low HGI group ( HR=1.685, 95% CI 1.023 to 2.774). CKD risk increased with increasing HGI tertiles ( P for trend=0.028). Conclusion:High HGI is associated with an increased risk for CKD in the nondiabetic population, indicating that HGI may help identify individuals at high risk for CKD.

Objective:To investigate the value of atropine administration before tracheal intubation under general anesthesia in the elderly patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)biopsy.Methods:This was a case-control study.A total of 87 elderly hospitalized patients receiving chest enhanced CT test suggesting the risk of lung cancer with enlargement of mediastinal lymph nodes in 7 regions were scheduled to undergo endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)biopsy under general anesthesia.The patients were randomly divided into two groups by flipping a coin: the atropine group(n=40)and the control group(n=47). The indicators for evaluating the application values of atropine included preoperative, intra-operative and postoperative systolic blood pressure(SBP), diastolic blood pressure(DBP), heart rate, oropharyngeal and airway secretion volume, oxygen saturation, operation time, positive diagnosis rate and postoperative adverse reactions.Results:SBP and DBP were lower in the atropine group than in the control group before endotracheal intubation(131.7±15.3 mmHg vs.140.7±13.7 mmHg, 79.1±7.6 mmHg vs.85.6±7.4 mmHg, t=2.885 and 4.061, P<0.05). There was no significant difference in SBP and DBP 10 min after endoscopic operation and 10 min after tracheal extubation between the atropine group versus the control group(SBP: 109.1±11.2 mmHg vs.105.0±12.2 mmHg, 136.9±23.0 mmHg vs.129.9±11.2 mmHg, DBP: 66.9±7.5 mmHg vs.68.0±8.3 mmHg, 77.6±10.9 mmHg vs.78.5±6.4 mmHg, t=-1.617, 0.687, -1.751 and 0.448, P>0.05). There was no significant difference in HR between the two groups before endotracheal intubation( t=1.416, P>0.05), while HR was higher in the atropine group than in the control group 10 min after endoscopic operation and 10 min after tracheal extubation( t=-3.323 and -2.181, P<0.01 and P<0.05). The change rates of SBP and DBP were lower in the atropine group than in the control group 10 min after endoscopic operation and 10 min after tracheal extubation( t=7.947, -6.962, -3.187 and -3.232, P<0.01). The change rate of HR was lower in the atropine group 10 min after endoscopic operation and was higher 10 min after tracheal extubation than in the control group( t=-6.467 and -4.131, P<0.01). There were significant differences in the volume of oropharyngeal and airway secretions and fingertip oxygen saturation between the two groups before endotracheal intubation and 10 min after tracheal extubation( t=-2.334, 2.759, -3.314 and -2.767, P<0.01). The endoscopic operation time was less in the atropine group than in the control group with no statistically significant difference[(25.9±5.7)min vs.(26.4±4.7)min, t=0.391, P>0.05]. There was no significant difference in postoperative adverse reactions between the atropine group versus the control group(34 patients or 85.0% vs.43 patients or 91.5%, χ2=1.247, P>0.05). Conclusions:The application of atropine before tracheal intubation under general anesthesia is beneficial to stabilizing the intraoperative blood pressure and heart rate, and can reduce the production of postoperative oropharyngeal and airway secretions in elderly patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration biopsy.

OBJECTIVE：To provide reference for r ational use of TCM decoction piece. METHODS ：Electronic questionnaire survey was conducted on the use （dose，ingredient number ）of TCM decoction piece prescriptions in 12 TCM hospitals from 10 provinces（regions，cities）. Through the hospital information system ，416 100 outpatient prescriptions of TCM decoction piece were collected from the First Affiliated Hospital of Henan University of TCM （our hospital ）during May 2016 to Apr. 2019，and were analyzed in terms of prescription dose ，the number of ingredients and use of TCM decoction pieces. At the same time ，the use of TCM decoction piece prescription were analyzed in different departments ，and the clinical application status of TCM decoction pieces prescription were investigated and relevant suggestions were put forward. RESULTS ：The average dose of TCM decoction piece prescriptions in 12 hospitals were 129.60-245.00 g，and the average number of ingredients were 11.90-18.25；the average dose of TCM decoction piece prescriptions in pediatric department was lower than other departments. The average dose of TCM decoction piece prescriptions in our hospital was 242.21 g；55.75％ of the prescription dose were distributed in 201-300 g，and 15.22％ were over 300 g. The average number of ingredients in prescriptions was about 15，and the prescriptions with 11-20 ingredients accounted for 87.75％，those with more than 20 ingredients accounted for 6.64％. Top 20 TCM decoction pieces in TCM prescriptions of our hospital had different degrees of overdose. Three decoction pieces with the highest frequency of overdose were Radix Curcumae processed by vinegar （85.51％），Atractylodes macrocephala stir-fried with bran （82.10％）and A. macrocephala（79.13％）. The number of TCM decoction piece prescriptions in internal medicine department accounted for 40.84％ in our hospital ；there were a lot of TCM prescriptions with dose exceeding 300 g（11.98％ and 18.69％）and the number of ingredients exceeding 18（14.60％ and 9.53％）in internal medicine department and surgery department. The proportion of pediatric TCM decoction piece prescriptions with more than 18 ingredients accounted for 24.09％. CONCLUSIONS ：The overall dosage of TCM decoction piece prescriptions is relatively high ，the number of ingredients is too much ，and the overdose of single-flavored TCM decoction piece is common. Internal medicine department and surgery department should focus on controlling the number of and the dosage of single-flavored decoction pieces of TCM prescriptions to standardize the prescribed dosage. Gynecology department needs to focus on controlling the dosage of single-flavored TCM pieces and pediatrics department should pay special attention to the use of prescription ingredients ，so as to ensure a more scientific and reasonable standard for the clinical application of TCM decoction piece.

To improve the standard of quality control of tazobactam and its preparations in China, national reference standard of tazobactam impurity A was developed. After tazobactam impurity A was synthesized, its structure was validated by infrared (IR), mass spectrometry (MS) and nuclear magnetic resonance (NMR), and its content uniformity and short-term stability were measured and investigated. Then, water content and residue on ignition of impurity A were determined, and its purity was determined using high performance liquid chromatography (HPLC) with 10 mmol/L ammonium acetate solution-acetonitrile (98∶2) as the mobile phase. Mass balance method was used to determine the content of the first batch of tazobactam impurity A national standard substance. Meanwhile, nuclear magnetic quantitative method was used to calculate the content, which was mutually verified with the mass balance method. The developed reference material of tazobactam impurity A is consistent with the maximum degradation impurity in tazobactam system applicability solution and the reference material of tazobactam related substance A contained in USP41. Within the 95% confidence range, the ratio of inter- and intra-bottle variance of impurity A after separation was 0.61 (< F0.05(11,12)), proving that the uniformity was satisfying. The contents of organic impurity, water content and inorganic impurity in impurity A were 0.90%, 1.24% and 0.25%, respectively. The content of impurity A was determined to be 97.6% by mass balance method, which was basically consistent with the result of nuclear magnetic quantitative method (97.1%). Under the condition of 25 °C, the area normalized purity of impurity A was 99.1% at 0, 3, 5 and 10 days, proving that the sample was stable at room temperature for 10 days. Finally the first batch of national standard substance of tazobactam impurity A was established successfully.