ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Humans ; Diabetic Nephropathies/pathology* ; Kidney/pathology* ; Biopsy ; Diabetes Mellitus, Type 2/pathology* ; Retrospective Studies ; Glomerular Filtration Rate ; Disease Progression

Objective:To evaluate the association between arterial lactate levels and complications within 30 days postoperatively in elderly patients undergoing pancreaticoduodenectomy.Methods:Elderly patients undergoing pancreaticoduodenectomy under selective general anesthesia in Beijing Hospital from July 2019 to December 2021 were enrolled.According to whether complications occurred within 30 days after operation, the patients were divided into complication group(C Group)and no complication group(N Group). General clinical data and lactic acid level before and after surgery were compared between the two groups.And the association between lactic acid level and complications within 30 days postoperatively was evaluated.Results:A total of 70 elderly patients were included in this study, of whom 22 patients had complications with proportion of 31.4%(22/70), including 2 cases of hemorrhage(2.9%, 2/70), one case of infection(1.4%, 1/70), 1 case of pneumonedema(1.4%, 1/70), 13 cases of pancreatic fistula(18.6%, 13/70), 5 cases of all-cause death postoperatively(7.1%, 5/70). There was no significant difference in baseline of arterial lactate level between two groups[0.70(0.50, 0.80)mmol/L vs.0.70(0.50, 1.20)mmol/L, Z=-1.150, P=0.250], while the lactate level at the end of the surgery was significantly higher in group C[1.60(0.90, 2.25)mmol/L]than in group N[1.00(0.80, 1.38)mmol/L]( Z=-2.396, P=0.017). The arterial lactate level at the end of the surgery was a risk factor for postoperative complications by multivariate analyses( OR=2.501, 95% CI: 1.154~5.418, P=0.020). Conclusions:Lactate level at the end of the surgery is related to early postoperative complications(within 30 days postoperatively)in elderly patients undergoing pancreaticoduodenectomy.Paying great attention to lactate monitoring at the end of the surgery may reduce the occurrence of perioperative complications in elderly patients undergoing pancreaticoduodenectomy.

Objective: To investigates the prevalence of depression and anxiety among middle school students at different times, and to provide a reference for mental health promotion among adolescents. Methods: A total of 1 505 middle school students, selected from Chongqing in 2021 by using multi stage stratified random sampling method, were surveyed by using the Center for Epidemiologic Studies Depression Scale(CSE-D) and Zung Self Rating Anxiety Scale (SAS). Results: At the beginning of the semester, 434(27.6%) and 601 students( 38.2 %) reported depressive and anxiety symptoms,respectively. While at the end of the semester showed that 463 cases (30.8%) were prone to depression, and 653 cases ( 43.4 %) reported depressive and anxiety symptoms,respectively. The detection rate of depressive symptoms at the end of the semester was significantly higher than that at the beginning of semester. (43.4%, 38.2 %, χ 2=8.55, P <0.05). Depressive of female students at the end of the semester( 52.8 %) was higher than that at the beginning of the semester(46.3%)( χ 2=6.19, P <0.05) The detection rate of anxiety symptoms in senior high school students at the end of the semester(44.9%) was significantly higher than that of at the beginning of the semester(28.6%) ( χ 2= 43.33 , P <0.01). No significant difference in anxiety symptoms boys and junior high school students between the beginning and the end of the semester ( χ 2=2.34, 0.71, P >0.05). Conclusion Substantial changes are observed in anxiety symptoms among female middle school students and depressive and anxiety symptoms among high school students in different periods of a semester. When investigating depression and anxiety of middle school students, time effect should be considered.

Objective:Heart failure(HF),a worldwide health condition,is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM)Xiaoyu Jiangzhi capsule(XYC)has long been in use in China to treat hyperlipidemia and inhibit platelet aggregation.This study explores the effects of XYC on heart failure(HF)and its detailed mechanisms.Methods:Isoproterenol(ISO,30 mg/kg)was injected intraperitoneally for 7 days to copy a HF model of 10-12 weeks old,20-30 g male mice.We then compared the CON(control)group,ISO(HF model)group,MET(metoprolol)group,and XYC group.Cardiac systolic function and left wall thickness were evaluated by echocardiograph.Using western blot analysis,we detected the proteins of calmodulin dependent protein kinase Ⅱ(CaMKII)and sarco/endoplasmic reticulum Ca2+-ATPase(Serca).Further-more,tsA201 cells were cultured and the human CaV1.2 calcium channel current(hCaV1.2)were detected by patch clamp experiments.Results:XYC reduced HF,inhibiting the protein expression of CaMKII,but Serca did not change signifi-cantly.Moreover,XYC inhibited the peak amplitude of the hCaV1.2 current,depolarizing shifted the activation curve 27.6 mV,and shifted the inactivation curve toward a positive potential 17.6 mV.The fraction recovered from inaction was reduced in XYC group compared with that in CON group.Conclusion:XYC could inhibit ISO-induced HF by reducing the Ca2+/CaMKII signaling pathway in mice.

OBJECTIVE：To establish the method for simultaneous determination of 5-fluorouracil（5-FU）and its metabolites 5-fluoro-5，6-dihydrouracil （5-FUH2） in human plasma ，and apply it in the clinic. METHODS ：After plasma samples were processed twice by ethyl acetate ，UPLC-MS/MS method was adopted using 5-bromouracil （5-Bru） as internal standard. The determination was performed on Acquity UPLC HSS T 3 column with mobile phase consisted of methanol-water （30 ∶ 70，V/V）at the flow rate of 0.3 mL/min. The column temperature was 20 ℃，and sample size was 5 μL. An electrospray ion source was used to carry out negative ion scanning with multiple reaction monitoring. The capillary voltage was 1.5 kV；the taper hole voltage was 20 V；the desolvent temperature was 450 ℃；the desolvent air flow was 850 L/h；the cone hole gas velocity was 50 L/h. The ion transitions for quantitative analysis were m/z 129.00→41.90（5-FU），m/z 130.87→82.92（5-FUH2），m/z 189.00→42.10（5-Bru）， respectively. From Aug. to Oct. 2020，10 patients with advanced colorectal cancer were treated with continuous intravenous drip of 5-FU for 46 hours were collected from Harbin Medicinal University Cancer Hospital. Steady-state plasma concentration of 5-FU and plasma concentration of 5-FUH2 were determined at 18-30 h of continuous intravenous drip. The area under the curve （AUC）for 5-FU and concentration ratio of 5-FUH2/5-FU were calculated. RESULTS ：The linear range of 5-FU and 5-FUH2 were 20 to 1 000 μg/mL（R 2＞0.990）. The quantification limits were 20 ng/mL. RSDs of precision test were all lower than 20％，and relative error ranged ±10％. The extraction recovery and matrix effects didn ’t affect the determination of substance to be measured. Among 10 patients with advanced colorectal cancer ，the steady-state concentration of 5-FU were 180.04-622.83 ng/mL，and AUC of 5-FU ranged from 8.28 to 28.65 mg·h/L. The concentration of 5-FUH2 ranged 336.48-948.43 ng/mL，and concentration ratio of 5-FUH2/ 5-FU ranged 0.93-4.21. AUC of 5-FU in 10 patients had about 3-4 fold individual differences. CONCLUSIONS ：The established method has good precision and accuracy ，high sensitivity ，and simple operation. It can be used for plasma monitoring of 5-FU in patients with advanced colorectal cancer.

Objective: To explore how to select osteotomy line and its significance in mandibular distraction osteogenesis in infants and young children. Methods: From May 2013 to July 2018, 208 infants and young children with mandibular deformity were admitted to the Department of Oral and Maxillofacial Surgery, Guangzhou Women and Children Medical Center, including 131 males and 77 females, with the age range of 8 days to 4 years, mean age of 6 months. Their clinical records were retrospectively analyzed. There were 162 cases of Robin sequence, 37 cases of the first and branchial arch anomalies, 2 cases of Treacher-Collins syndrome, and 7 cases of other congenital malformations. During the distraction osteogenesis, different osteotomy lines were selected according to the characteristics of the mandibular deformity: (1) For short mandibular body, the straight osteotomy line was used to extend the mandibular body. (2) For short mandibular ramus, a polygonal osteotomy line was used to extend the ramus. (3) For the increased mandibular angle, a curved osteotomy line was used to change the angulation. Results: Linear osteotomy was used in 38 patients, polygonal line osteotomy were used in 129 patients, and curved osteotomy was performed in 41 patients. Among them, 4 patients with linear osteotomy had deciduous embryo injury, 6 patients with linear osteotomy and 2 patients with polygonal osteotomy had open occlusion, and patients with curved osteotomy did not have tooth and mandible damage, or malocclusion. All patients were followed up for 3 months to 5 years. The average follow-up time was 6.2 months. All osteotomy healed well, without osteonecrosis or nonunion. Conclusions For the mandibular distraction osteogenesis, osteotomy line could be individualized, according to the characteristics of mandibular deformity of infants and young children, which can reduce complications such as dental damage and open occlusion.

In recent years,capecitabine is widely used in clinical practice.Hand-foot syndrome is a dose-limiting toxicity, often manifested as numbness in the hands and feet,sensation of dullness,tingling,skin swelling or erythema,scaling,blisters or seri-ous pain.Its occurrence has seriously affected the chemotherapy effect and daily life of patients.Genetic mutations of capecitabine met-abolic enzymes play an important role in the drug efficacy and side-effect.In particular,the relationship between gene polymorphisms of CDA,CES,TP,DPD,TYMS,MTHFR and hand-foot syndrome has been widely investigated and achieved by researchers.This arti-cle reviews the relationship between capecitabine metabolizing enzymes and hand-foot syndrome in order to provide a reference for i-dentifying the biological target of hand-foot syndrome caused by capecitabine chemotherapy.

OBJECTIVES: To explore the genetic variation sites of caveolin （CAV） and their correlation with sudden unexplained death （SUD）. METHODS: The blood samples were collected from SUD group （71 cases）, coronary artery disease （CAD） group （62 cases） and control group （60 cases）, respectively. The genome DNA were extracted and sequencing was performed directly by amplifying gene coding region and exon-intron splicing region of CAV1 and CAV3 using PCR. The type of heritable variation of CVA was confirmed and statistical analysis was performed. RESULTS: A total of 4 variation sites that maybe significative were identified in SUD group, and two were newfound which were CAV1： c.45C>T （T15T） and CAV1：c.512G>A （R171H）, and two were SNP loci which were CAV1：c.246C>T （rs35242077） and CAV3：c.99C>T （rs1008642） and had significant difference （P<0.05） in allele and genotype frequencies between SUD and control groups. Forementioned variation sites were not found in CAD group. CONCLUSIONS The variants of CAV1 and CAV3 may be correlated with a part of SUD group.
Caveolins/genetics* ; Coronary Artery Disease ; Death, Sudden/etiology* ; Exons ; Genotype ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

Objective:To explore the role of clinical pharmacists in the development of individualized drug treatment regimens for the osteosarcoma children with irregular body weight .Methods:Clinical pharmacists involved in the calculation of body weight surface area increased to that of adult for one case of osteosarcoma child during the chemotherapy , comparatively analyzed the suitable calcula-tion formula of surface area for the children in our country and helped clinicians make accurate dose of chemotherapy drugs .Mean-while, according to the pathological and physiological characteristics of the child , clinical pharmacist also provided advice on adjuvant drug use such as antiemetic regimen etc .Results:Physicians adopted the suggestions of clinical pharmacists and the chemotherapy was successfully completed .Overdose adverse reactions were avoided without the use of foreign general calculation formula of body surface area for the overweight child , and inadequate dose was also avoided for the conservative treatment , which could lower the risk of re-duced potential anticancer efficacy .Conclusion:Clinical pharmacists can help doctors perform safer and more effective drug treatment program and reduce adverse drug reactions in the treatment of special patients through participation in the development of individualized medication for cancer children to obtain maximum profit .