OBJECTIVE To mine adverse drug event （ADE） signals of lacosamide， and to provide references for clinically safe drug use. METHODS ADE data for lacosamide reported to the United States FDA adverse event reporting system from January 1， 2009， to December 31， 2022， were collected. Data mining was conducted using the reporting odds ratio method and Bayesian confidence propagation neural network method. Classification statistics were performed using the system organ class （SOC） and preferred terms （PT） from ADE terminology set of Medical Dictionary for Regulatory Activities （Version 25.0）. RESULTS A total of 21 360 lacosamide ADE reports were received， identifying 203 ADE signals across 24 SOCs， with 19 signals not included in the drug’s instruction. The top five PTs ranked by occurrence frequency were medication overdose， technical errors during device use， product use issues， intentional product misuse， and therapy discontinuation. The top five PTs ranked by signal strength were changes in seizure presentation type， congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， brain surgery， and vagus nerve stimulator implantation. ADEs not recorded in the drug instruction included congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， mitochondrial DNA mutation， dissociative identity disorder， and congenital auricular anomaly. CONCLUSIONS For lacosamide-induced ADEs that occur frequently and are already listed in the drug’s instructions， such as bradycardia and atrioventricular block， the clinical application should be careful and attentive， adjusting the dosage timely according to the patient’s condition to avoid severe ADEs. Newly discovered suspect ADEs， such as congenital hypoplasia of depressor anguli oris muscle， mitochondrial DNA mutation， overmature infant， dissociative identity disorder， pigmenturia， behavioral disorders， and dissociative disorders， should be vigilantly recognized to ensure the safety of drug use.

Objective:To study the efficacy of astragalus polysaccharides combined with cisplatin in the treatment of malignant peritoneal effusion caused by ovarian cancer and its effect on drug resistance genes.Methods:Patients with malignant peritoneal effusion caused by ovarian cancer from January 2015 to December 2018 in Guangrao Country Hospital of Traditional Chinese Medicine were selected as the study subjects. They were divided into astragalus polysaccharide combined with cisplatin treatment group and cisplatin treatment group according to the odd and even number of hospital number, with 60 patients in each group. The patients in cisplatin treatment group were given peritoneal perfusion with cisplatin 75 mg/m 2 and 0.9% sodium chloride injection 50 ml, and the drainage tube were clamped once every 3 d. Treatment continued for 21 d. The patients in astragalus polysaccharide combined with cisplatin treatment group were treated with astragalus polysaccharide 250 ml intravenous drip once a day on the basis of cisplatin treatment group, and treatment continued for 21 d. The peritoneal effusion was pumped by drainage tube and was detected after treatment. The differences in adverse reactions, ascites recurrence time and median survival time were compared between two groups. Changes in inflammatory factors and T lymphocytes before and after treatment were detected and compared. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect resistance genes in peritoneal effusions including glutathione S-transferase π (GST-π), P-glycoprotein (P-gp) and multidrug resistance gene 1 (MDR1) mRNA and protein expression. Results:The incidence of gastrointestinal symptoms, Ⅲ-Ⅳ class myelosuppression and Ⅲ-Ⅳ class hepatorenal damage in the astragalus polysaccharide combined with cisplatin treatment group were significantly lower than those in the cisplatin treatment group [38.3%(23/60) vs. 66.7%(40/60), 6.7%(4/60) vs. 33.3%(20/60), 13.3%(8/60) vs. 45.0%(27/60)], while the ascites recurrence time and median survival time were significantly higher than those in the cisplatin treatment group [(6.3 ± 1.7) months vs. (5.5 ± 1.1) months, (15.2 ± 2.4) months vs. (11.7 ± 1.6) months], and there were significant differences ( P<0.05). There were no statistical differences in tumor necrosis factor (TNF)-α, interleukin(IL)-2, IL-6 between two groups before treatment ( P>0.05), after treatment in astragalus polysaccharide combined with cisplatin treatment group, the levels of TNF-α and IL-6 were lower [(21.8 ± 3.5) ng/L vs. (27.5 ± 4.1) ng/L, (17.2 ± 2.2) ng/L vs. (21.9 ± 2.7) ng/L] and the level of IL-2 was higher [(15.5 ± 1.6)ng/L vs. (12.7 ± 1.1) ng/L], and there were significant differences ( P<0.05). There was no statistical differences in CD 3+, CD 4+ and CD 8+ between two groups before treatment ( P>0.05), after treatment in astragalus polysaccharide combined with cisplatin treatment group, the levels of CD 3+, CD 4+ and CD 8+ were higher [(55.3 ± 3.9)% vs. (48.9 ± 3.2)%, (33.2 ± 3.4)% vs. (30.4 ± 2.2)%, (21.4 ± 3.1)% vs. (17.6 ± 1.9)%], and there were significant differences ( P<0.05). After treatment, the levels of GST-π, P-gp and MDR1 gene mRNA and protein expressions in astragalus polysaccharide combined with cisplatin treatment group were significantly lower than those in the cisplatin treatment group, and there were significant differences ( P<0.05). Conclusions:Astragalus polysaccharide can improve immune function and reduce drug resistance gene expression in patients with malignant peritoneal effusion caused by ovarian cancer, which can significantly improve the efficacy of cisplatin in the treatment of malignant peritoneal effusion caused by ovarian cancer and reduce adverse reactions.

Objective:To investigate the value of serum microRNA-92a (miR-92a) and microRNA-146a (miR-146a) expression levels combined with lung ultrasound score (LUS) in predicting the severity and prognosis of acute respiratory distress syndrome (ARDS).Methods:116 patients with ARDS admitted to Danzhou People's Hospital from January 2017 to March 2020 were enrolled. On the day of admission, the expression levels of serum miR-92a and miR-146a were detected by real-time fluorescent quantitative reverse transcript-polymerase chain reaction (RT-PCR), and pulmonary ultrasound examination was performed in 12 lung regions, with the total score as LUS score. The difference of each index was analyzed among the ARDS patients with different 28-day prognosis (survival group and death group) and different severity [mild group: 200 mmHg < oxygenation index (OI) ≤ 300 mmHg (1 mmHg = 0.133 kPa), moderate group: 100 mmHg < OI≤200 mmHg, severe group: OI≤100 mmHg]. Multivariate Logistic regression was used to analyze the risk factors of death in patients with ARDS. Receiver operating characteristic (ROC) curve was drawn to analyze the value of miR-92a and miR-146a combined with LUS score in predicting the death of patients with ARDS.Results:116 ARDS patients were included, 39 cases in the death group, 77 cases in the survival group; 20 cases in the mild group, 38 cases in the moderate group and 58 cases in the severe group. The expression levels of serum miR-92a, miR-146a and LUS score in the death group were significantly higher than those in the survival group [miR-92a (2 -ΔΔCt): 3.75±1.64 vs. 2.10±0.78, miR-146a (2 -ΔΔCt): 1.93±0.72 vs. 0.76±0.20, LUS score: 25.80±4.75 vs. 13.40±3.60, all P < 0.01]. With the aggravation of ARDS patients, the expression levels of serum miR-92a and miR-146a and LUS score gradually increased ( F values were 8.115, 6.740 and 6.216 respectively, all P < 0.01). The expression levels of serum miR-92a, miR-146a and LUS score in severe group were significantly higher than those in the moderate group and mild group [miR-92a (2 -ΔΔCt): 3.65±1.62 vs. 2.87±1.16, 1.94±0.68; miR-146a (2 -ΔΔCt): 1.85±0.58 vs. 1.30±0.51, 0.68±0.17; LUS score: 24.15±4.65 vs. 18.60±4.20, 12.20±3.15, all P < 0.01]. Multivariate Logistic regression analysis showed that low OI [odds ratio ( OR) = 2.748, 95% confidence interval (95% CI) was 1.913-6.225, P = 0.024], high LUS score ( OR = 1.685, 95% CI was 1.183-2.758, P = 0.016), high expression levels of serum miR-92a ( OR = 2.560, 95% CI was 1.806-5.627, P < 0.001) and miR-146a ( OR = 1.984, 95% CI was 1.375-3.816, P = 0.008) were independent risk factors for the death of ARDS patients. ROC curve analysis showed that the area under ROC curve (AUC) of patients with ARDS predicted by miR-92a and miR-146a combined with LUS score was significantly higher than that predicted by the three alone (0.918 vs. 0.842, 0.825, 0.807, all P < 0.01), and the sensitivity (94.0%) and specificity (85.2%) were higher. Conclusion:The expression levels of serum miR-92a, miR-146a and LUS score are related to the severity and prognosis of the patients with ARDS, and the combination of the three indicators has better value in predicting the prognosis of the patients with ARDS.

OBJECTIVE:To improve community pharmaceutical care so as to promote the rational drug use of community resi-dent and improve the quality of life. METHODS:By analyzing the situation of community pharmaceutical care,the pharmaceutical care of community pharmacists was improved by changing pharmaceutical care mode,actively developing the propaganda of ratio-nal drug use,strengthening retraining of clinical pharmacists. RESULTS:With the help of Hongkou district quality control group, many hospitals of the district signed thepharmaceutical linkage assistance agreement. Through the efforts of Hongkou district quality control group and many hospitals,community pharmaceutical care was improved and the propaganda of rational drug use has achieved certain results. CONCLUSIONS:Through exploration and practice,the pharmaceutical care levels of community phar-macists have been improved and the rational drug use of community residents has been promoted.

Objective To develop a novel skin microdialysis technology in vivo,and to determine the pharmacokinetic of ba-icalin after transdermal administration in rats. Methods An HPLC-MS/MS method used for the determination of baicalin in skin mi-crodialysis samples was established ,SD rats were pretreated with skin microdialysis operation under anesthesia , and then the baicalin gel was applied to the skin surface of probe in vivo.The baicalin concentration of skin microdialysates was determined , the time curve of baicalin concentration was drawn and the topical pharmacokinetics parameters of percutaneous absorption was calculated. Results Baicalin was optimized at the transitions m/z 447.3→271.2.The linearity correlation was good and the assay exhibited good precision and accuracy.The subcutaneous probe recovery of baicalin in vivo was(24.40 ±0.91)%and was stable over the 240 min study peri-od.Baicalin could be detected in the microdialysis samples after transdermal administration , and its concentration continued to rise in 8 h.AUC0-t in skin tissue was(50.04 ±34.17) mg· min· L-1. Conclusion The method of skin microdialysis in vivo could be used in the local pharmacokinetic research of baicalin.

ObjectiveTo investigate the expression characteristics of Caspase-8 in gastric carcinoma tissues and its correlation with clinical pathological features.Methods The mRNA and protein of Caspase-8 in gastric carcinoma and its surrounding tissues were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry,respectively.ResultsThe Caspase-8 mRNA in gastric carcinoma tissues was obviously lower than that in its surrounding ones (0.154±0.065 vs 0.394±0.107,t =14.04,P ＜0.01),which was correlated with lymph node metastasis,tumor stage,differentiation grade (P＜0.01).The Caspase-8 protein in gastric carcinoma tissues was also significantly lower than that in its surrounding ones (31.48％ vs 85.19％,x2 =32.04,P ＜ 0.01),which was correlated with tumor stage,differentiation grade (P＜0.05).ConclusionsCaspase-8 is low-expressed in gastric carcinoma,which may play an important role in the occurrence and progression of gastric carcinoma.

Objective To analyze the disposition characteristic of LGT fingerprints and the related fingerprints for advanced gastric carcinoma patients when the LGT fingerprints changing. Methods SELDI and CM10 protein chip was used to detect the serum protein fingerprints of 81 cased of advanced gastric cancer patients. After 1 year follow-up, all the patients were detected by SELDI again. According to the expression condition of LGT fingerprints, the patients were divided into 4 groups: A group(LGT changing from negative to positive) 25 cases, B group (LGT changing from positive to negative) 15 cases, C group (LGT fingerprints keeping negative) 29 cases and D group (LGT fingerprints keeping positive) 12 cases. The influencing factor should be rejected. And the remaining fingerprints were LGT fingerprints' subtypes and therelated fingerprints. The different proteomic fingerprints were analyzed by Biomarker Wizard 3.1 Software.Results After rejecting the influencing fingerprints, the up-regulation fingerprints in A group were 11473, 11821, 11664, 11409, 11552 and 11947 (M/Z), and no down-regulation fingerprints. In B group, 3264 was upregulation, and 6523, 11509, 11669, 11413, 11351 and 6483 were down-regulation. In C and D group, there was not statistically differential protein fingerprint. Conclusion M/Z up-regulating fingerprints including 11473, 11821, 11664, 11409, 11552 and 11947 can be regarded as the subtype of LGT when it changing from negative to positive; down-regulating including 11509, 11669, 11413 and 11351 can be regarded as the subtype of LGT when it changing from positive to negative; 3264 up-regulating and 6523 and 6483 downregulating can be regarded as the related fingerprints when LGT changing from positive to negative; and when LGT keeping negative or positive in patients with advanced gastric cancer, there was no differential protein fingerprints.

OBJECTIVE:To investigate the perioperative prophylactic utilization of antibiotics in cataract patients in ophthalmology department of our hospital.METHODS:100 cases of cataract surgery in 2009 were randomly collected from our hospital.Category of antibiotics,administration time point,medication time,wound healing and drug costs in hospitalization period were analyzed statistically and the rationality of above indexes was evaluated.RESULTS:100 cases all received prophylactic antimicrobials by local and systematic administration in the perioperative period(100%).Drugs for systematic administration contained Levofloxacin(n=67,67%),Cefuroxime sodium for injection(n=25,25%),Clindamycin phosphate injection(n=2,2%) and Ceftazidime for injection(n=6,6%).63 cases were only given drugs 30 min before operation(63%);12 cases were given medicine 30 min before operation and within 24 h after operation(12%);above situation accounted for 75%.25 cases were given medicine before operation and within 24 h after operation(25%),in which the average medication duration was 2.5 days and the longest was 4 days.CONCLUSION:The irrational use of drugs in our hospital manifests inappropriate selection and too long use of antibiotics after operation.The interference of perioperative prophylactic utilization of antibiotics should be reinforced and it is urgent to intensify consciousness of physicians about rational use of antibiotics in perioperative period.

Fifty-four cases of woman with lactation insufficiency were treated with acupuncture at acupoints Shaoze (SI 1), Danzhong (CV 17), Rugen (ST 18), Pishu (BL 20), Zusanli (ST 36) and Sanyinjiao (SP 6), and 42 cases got significant effect that the milk could fully meet baby's nutritional requirement, 9 cases got improvement, 3 cases discontinued the treatment.

OBJECTIVETo observe the effective mechanism and side effects of thalidomide to multiple myeloma (MM).

METHODSTen cases of MM were studied, of which 3 were previously untreated and 7 refractory or relapsed. Bone marrow microvascular density (MVD) was detected by factor-VIII related antigen and CD(34) immunohistological staining and serum concentration of vascular endothelial growth factor (VEGF) before and after treatment was determined by ELISA. The initial dosage of thalidomide was 100 approximately 200 mg/d with a weekly escalation of 50 mg/d to 450 approximately 650 mg/d. The therapeutic effectiveness is classified into partial remission, improvement and uneffective according to the decrease of serum M protein and bone marrow myeloma cells. Anemia, renal function and blood electrolytes were also observed.

RESULTSBefore treatment, MVD was 73.32 +/- 28.80 and 32.30 +/- 12.50 in MM and control group, respectively, (P < 0.01). MVD in MM group decreased to 56.12 +/- 19.34 after treatment, and was of significant difference (P < 0.05) as compared to the pretreatment value. However, there was still a significant difference as compared to control (56.12 +/- 19.34 vs 32.30 +/- 12.50, P < 0.01). The concentration of VEGF significantly decreased after treatment [from (178.23 +/- 26.56) ng/L to (78.48 +/- 19.98) ng/L, P < 0.01)]. The total effective rate was 70%. There were no serious side effects.

CONCLUSIONMVD and VEGF concentration were decreased obviously by thalidomide treatment. The dosage of 450 approximately 650 mg/d might be effective in refractory or initial MM.

Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antigens, CD34 ; analysis ; Bone Marrow ; blood supply ; drug effects ; Constipation ; chemically induced ; Endothelial Growth Factors ; blood ; Fatigue ; chemically induced ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; blood ; Lymphokines ; blood ; drug effects ; Male ; Middle Aged ; Multiple Myeloma ; blood ; drug therapy ; pathology ; Nausea ; chemically induced ; Sleep Wake Disorders ; chemically induced ; Thalidomide ; adverse effects ; therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; von Willebrand Factor ; analysis