Objective To investigate the clinical efficacy of Wuhu Decoction plus Tingli Dazao Xiefei Decoction combined with Budesonide atomization for the treatment of pediatric bronchopneumonia with phlegm-heat obstructing the lung syndrome,and to observe its effect on inflammatory response.Methods Seventy children with bronchopneumonia of phlegm-heat obstructing the lung type were randomly divided into an observation group and a control group,with 35 cases in each group.The children in the control group were treated with atomized inhalation of Budesonide suspension,and the children in the observation group were treated with Wuhu Decoction plus Tingli Dazao Xiefei Decoction orally on the basis of treatment for the control group.Both groups were treated for a period of 7 days.The changes in the traditional Chinese medicine(TCM)syndrome scores and the serum levels of inflammatory factors of interleukin 6(IL-6),procalcitonin(PCT),and hypersensitive C-reactive protein(hs-CRP)in the two groups were observed before and after the treatment.Moreover,the clinical efficacy,time for the relief of symptoms and signs,and the incidence of adverse reactions in the two groups were compared.Results(1)After 7 days of treatment,the total effective rate of the observation group was 91.43%(32/35),and that of the control group was 71.43%(25/35).The intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores of the children in both groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the time for the relief of symptoms and signs such as wheezing,cough,lung rales,constipation and fever in the observation group was significantly shortened compared with that in the control group(P＜0.01).(4)After treatment,the serum IL-6,PCT and hs-CRP levels in both groups were significantly lower than those before treatment(P＜0.05),and the reduction in the observation group was significantly superior to that in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 5.71%(2/35)and that in the control group was 8.57%(3/35),while the difference was not statistically significant between the two groups(P＞0.05).Conclusion Wuhu Decoction plus Tingli Dazao Xiefei Decoction combined with Budesonide atomization exert certain effect for the treatment of pediatric bronchopneumonia with phlegm-heat obstructing the lung syndrome,which can effectively relieve the clinical symptoms and alleviate the inflammatory response of the children.

Objective To study the acupoint selection and medication rules of acupoint application as an advantageous therapy in treating stroke.Methods The clinical literature from CNKI,Wanfang,CBMdisc,and other databases were searched,and Excel 2013 was used to count the frequency of disease,acupoint selection,and medication,and to analyze the acupoint selection rules using SPSS 25.0 and SPSS Modeler.Results Finally,523 articles were included in the literature,among which,the literature on the treatment of post-stroke constipation with acupoint patch was the most,and the related literature was further screened to analyze the acupoint selection and medication rules,and it was concluded that the most frequently applied acupoints of acupoint application for the treatment of post-stroke constipation were Shenque(RN8),Tianshu(ST25),Zhongwan(RN12),Zusanli(ST36),and the acupoints were mainly taken from conception vessel,stomach meridian and gallbladder meridian,and the core prescriptions were Shenque,Tianshu,Zhongwan,Qihai(RN6),Guanyuan(RN4),Zusanli.For the treatment of post-stroke constipation,acupoint application is often used with Rhei Radix et Rhizoma,Aurantii Fructus Immaturus,Cortex Magnoliae Officinalis,Natrii Sulfas Exsiccatus and Borneolum Syntheticum,among which,warm and cold nature drugs are mainly used,and bitter drugs are most frequently used among five flavors,and most frequently enter to the spleen meridian;and the core prescription is Rhei Radix et Rhizoma,Aurantii Fructus Immaturus,Cortex Magnoliae Officinalis,Natrii Sulfas Exsiccatus and Borneolum Syntheticum.Conclusion Acupoint application is an advantageous treatment for treating post-stroke constipation.The selection of acupoints was based on the conception vessel and stomach meridian,and the medication used were mainly focusing on those with functions of unblocking the bowels and directing qi downward,supplemented by strengthening the spleen and benefiting qi,warming the meridians and nourishing the blood.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

AIM:To investigate the anti-fibrotic effect of Panax notoginseng saponins(PNS)in arecoline(ANE)-induced oral submucous fibrosis,and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glu-tamate-cysteine ligase catalytic subunit(GCLC)signaling pathway.METHODS:CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line Ha-CaT.The results of CCK-8 were used to select 75 mg/L arecoline,and 25,50 and 100 mg/L PNS as subsequent experi-mental concentrations.The cells were set as blank control group,model group,and low,medium and high doses(25,50 and 100 mg/L)of PNS groups.The protein and mRNA expressions of collagen type I(COL-I),E-cadherin,Nrf2,GCLC and glutathione reductase(GR)in each group were detected by Western blot and RT-qPCR.Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus.Biochemical kits were used to detect the content of glutathione(GSH),nicotinamide adenine dinucleotide phosphate(NADPH)and malondialdehyde(MDA),and superoxide dis-mutase(SOD)activity in each group of cells.DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species(ROS).RESULTS:Compared with the blank control group,the protein and mRNA expression of COL-I in the model group was up-regulated,and the protein and mRNA levels of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were down-regulated.The content of NADPH,MDA and ROS in the cells increased,and the content of GSH and the activity of SOD was significantly reduced.Compared with the model group,the protein and mRNA expression of COL-I was down-regulated,and the protein and mRNA expression of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups.Compared with the model group,the content of NADPH,MDA and ROS in cells decreased,and the content of GSH and the activity of SOD was significantly enhanced(P<0.05 or P<0.01).CON-CLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells,and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway,thereby resisting oxidative stress and improving oral submucosal fibrosis.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease(CHD)in offspring.Methods The parents of children with simple CHD aged 0 to 1 year(n=683)were recruited as the case group,while the parents of healthy children aged 0 to 1 year(n=740)served as the control group.A case-control study was conducted,and a questionnaire was used to collect information on perinatal exposures.After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching,the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined,as well as the cumulative effects of smoking and drinking on CHD risk.Results Maternal active smoking(OR=2.91,95%CI:1.60-5.30),passive smoking(OR=1.94,95%CI:1.56-2.42),and alcohol consumption(OR=2.59,95%CI:1.89-3.54),as well as paternal smoking(OR=1.52;95%CI:1.22-1.90)and drinking(OR=1.48,95%CI:1.19-1.84),were associated with an increased risk of CHD in offspring.There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring(P>0.05).The more parents'smoking and drinking behaviors during the perinatal pregnancy,the higher the risk of CHD in their offspring(OR=1.50,95%CI:1.36-1.65).Conclusions Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring,and there is a cumulative effect on CHD risk,suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.

Objective To investigate the application value of arthroscopic three-approach combined with elliptical tunnel technique in anterior cruciate ligament(ACL)reconstruction.Methods A prospective analysis was conducted on 104 patients with ACL injury admitted to our hospital.They were randomly divided into the observation group and the control group according to a random number table method,with 52 cases in each group.All patients in both groups underwent ACL reconstruction.The patients in the observation group were treated with the arthroscopic three-approach combined with elliptical tunnel technique,while the patients in the control group were treated with the traditional anteromedial approach and elliptical tunnel technique.The surgical related indicators,parameters of postoperative bone tunnel positioning,postoperative graft maturation,knee stability(Lachman test),Lysholm score of knee function,and complications of patients were compared between the two groups.Results The time of getting out of bed with crutches,time of walking without crutches and recovery time of patients in the observation group were shorter than those in the control group(P<0.05).The A/B value of patients in the observation group was greater than that in the control group,and the a/c and α were smaller than those in the control group(P<0.05).The signal/noise quotient(SNQ)of the proximal,middle,and distal grafts 6 and 12 months after surgery of patients in the observation group were lower than those in the control group(P<0.05).At 6 months postoperatively,the knee stability of patients in the observation group was better than that in the control group,and the Lysholm score of knee function was higher than that in the control group(P<0.05).There was no significant difference in the incidence of postoperative complications between the two groups(P>0.05).Conclusion Arthroscopic three-approach combined with elliptical tunnel technique can improve the morphology of bone tunnel,promote graft maturation,shorten postoperative recovery process,and improve knee function in ACL reconstruction,with high safety.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To analyze the risk factors for late-onset hemorrhagic cystitis(LOHC)after allogeneic hematopoietic stem cell transplantation(allo-HSCT),the risk factors for the progression of LOHC to severe LOHC,and the effect of LOHC on survival.Methods:The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed.The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis.Then,the differences in overall survival(OS)and progression-free survival(PFS)between different groups were analyzed.Results:The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows:age≤45 years old(P=0.039),intensified conditioning regimen with fludarabine/cladribine and cytarabine(P=0.002),albumin ≤ 30 g/L on d30 after transplantation(P=0.007),CMV-DNA positive(P=0.028),fungal infection before transplantation(P=0.026),and the occurrence of grade Ⅱ-Ⅳ aGVHD(P=0.006).In the transplant patients who have already developed LOHC,the occurance of LOHC within 32 days after transplantation(P=0.008)and albumin ≤ 30 g/L on d30 after transplantation(P=0.032)were independent risk factors for the progression to severe LOHC.The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC(P=0.041).Conclusion:For the patients aged ≤ 45 years old and with intensified conditioning regimen,it is necessary to be vigilant about the occurrence of LOHC;For the patients with earlier occurrence of LOHC,it is necessary to be vigilant that it develops into severe LOHC.Early prevention and treatment of LOHC are essential.Regular monitoring of CMV-DNA and albumin levels,highly effective antiviral and antifungal therapies,and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.