OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

Gout is a metabolic disease closely associated with hyperuricemia and urate deposition. Because of the complex pathogenesis， high morbidity， multiple complications， and increasingly young patients， gout has received worldwide attention. Currently， western medicine mainly treats gout by lowering the uric acid level and reducing inflammation， which， however， causes serious adverse reactions and has contraindications. Phellodendri Chinensis Cortex （PCC） is the dried bark of Phellodendron chinense， with the effects of clearing heat， drying dampness， purging fire， detoxifying， and treating sores. Studies have shown that PCC and its active components have anti-inflammatory， pain-relieving， uric acid-lowering， and anti-gout activities， with extensive sources and high safety. PCC and its active components could prevent and treat gout through multi-targets and multi-pathways， whereas the systematic review remains to be carried out. Therefore， this paper summarized the pharmacological activities and mechanisms of PCC and its active components in the treatment of gout. The available studies have shown that PCC and its active components exert the anti-gout effect by lowering the uric acid level， reducing inflammation， alleviating oxidative stress， and regulationg intestinal flora， and protecting the kidneys. Particularly， the active components represented by alkaloids contribute obviously to the therapeutic effect of of PCC. Herein， we analyzed the problems and future development of the research on PCC， aiming to provide theoretical support and a scientific basis for the research and development of new drugs against gout.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To mine and analyze the adverse event data of polatuzumab vedotin(Pola)and fam-trastuzumab deruxtecan-nxki(T-Dxd),so as to provide reference for clinical medication safety.Methods The adverse events reported from January 1,2004 to June 7,2023 were extracted based on openFDA database.The suspicious risk signals were screened by the Open Vigil 2.1 data platform and ranked by signal strength and frequency of occurrence;then ADEs were classified by reference to the MedDRA 26.0.Results A total of 7 164 and 22 870 ADE reports related to Pola and T-Dxd were obtained,and 104 and 95 suspicious ADE signals were detected,respectively.According to the signal intensity,cytomegalovirus enterocolitis(ROR=416.94)for Pola and interstitial lung disease[reporting odds ratio(ROR)=82.55]for T-Dxd ranked first,both of which were recorded in the drug instructions.According to the frequency of occurrence,the two drugs were most frequently associated with death(n=111)and nausea(n=285),respectively.The risk of Pola was associated with 12 systems/organs,of which 26 risk signals were not documented in the drug instruction,and the risk of T-Dxd was associated with 13 systems/organs,of which 18 risk signals were not documented in the drug instruction.Conclusion By tapping the ADE after real-world administration of Pola and T-Dxd,physicians are prompted to pay attention to the risk of adverse reactions in clinical use and actively take preventive and therapeutic measures to ensure the safety of patients'medication.

To explore the clinical and genetic features of Aicardi-Goutières syndrome (AGS) caused by IFIH1 gene mutation.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

The 6-min walk test(6MWT)is an effective tool to assess the cardiopulmonary function and exercise tolerance,and is widely used in clinical practice to assess the exercise capacity in the patients with car-diopulmonary disease.Pulmonary hypertension(PH)is a serious cardiovascular disease manifested by a con-tinuous increase in pulmonary circulatory pressure,which limits the right heart function and eventually devel-ops into the right heart failure,moreover its clinical manifestations lack specificity,making diagnosis difficult.With the development of PH diagnosis and treatment technology,the medical staffs have paid more and more attention to the application of 6MWT in the diagnosis,treatment and prognosis of the patients with PH.This article reviews the characteristics of 6MWT,its application in PH,and its limitations and future prospects in order to help clinic to better understand the role of 6MWT in the whole disease course of the patients with PH,and encourage the medical care staffs to broadly apply and improve 6MWT to make it to be more reliable clinical evidence.