OBJECTIVE To summarize the current situation of pharmaceutical clinic service in our hospital over the past five years， and explore sustainable development strategies for service models of pharmaceutical clinics. METHODS A retrospective analysis was conducted on the consultation records of patients who registered and established files at the pharmaceutical clinic in our hospital from January 2019 to December 2023. Statistical analysis was performed on patients’ general information， medication- related problems， and types of pharmaceutical services provided by pharmacists. RESULTS A total of 963 consultation records were included， among which females aged 20-39 years accounted for the highest proportion （66.04%）； obstetrics and gynecology- related consultations accounted for the largest number of cases. Additionally， 80 patients attended follow-up visits at our hospital’s pharmaceutical clinic. A total of 1 029 medication-related issues were resolved， including 538 cases of drug consultations （52.28%）， 453 medication recommendations （44.02%）， 22 medication restructuring（2.14%）， and 16 medication education （1.55%）； the most common types of medication-related problems identified were adverse drug events（70.07%）. CONCLUSIONS Although the pharmaceutical clinic has achieved recognition from clinicians and patients， challenges such as low awareness among healthcare providers and the public persist. Future efforts should focus on strengthening information technology construction， enhancing pharmacist training， and establishing various forms of outpatient pharmaceutical service models.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Objective To observe the effect of hypoxia(HX)on autophagy and pyroptosis-related protein expression of interleukin(IL)-1β-induced chondrocytes,and explore its mechanism of cartilage protection.Methods The expression of Bcl2/adenovirus E1B interacting protein 3-like(BNIP3L/NIX)in normal and osteoarthritis chondrocytes was analyzed by bioinformatics method.The primary chondrocytes from the knee joints of C57BL/6J neonatal mice were extracted and assigned to control group,IL-1β group,HX group,or IL-1β+HX group.The cells were treated with 10 ng/mL IL-1β for 24 h to simulate osteoarthritis-like chondrocyte injury,and HX treatment was by incubation with 1%O2 for 24 h.The expression levels of collagen typeⅡ α1(COL2α1),matrix metalloproteinase 13(MMP13),a disintegrin and metalloproteinase with thrombospondin 5(ADAMTS5),nucleotide-binding oligomerization domain-like receptor 3(NLRP3),gasdermin D N-terminal domain(GSDMD-N),apoptosis-associated speck-like protein containing a CARD(ASC),IL-18,hypoxia induced factor 1α(HIF1α),NIX,Beclin1,microtubule-associated protein-light chain 3(LC3),and p62 proteins were detected by Western blotting in each group.Results Bioinformatics analysis showed that the expression of NIX was lower in osteoarthritis chondrocytes than in normal chondrocytes.Western blotting showed that compared to the control group,the IL-1β group showed significant decreases in COL2α1 and NIX protein expression(both P＜0.05)and significant increases in MMP13,ADAMTS5,NLRP3,GSDMD-N,ASC,IL-18 and HIF1α protein expression(all P＜0.01).Compared to the IL-1β group,the IL-1β+HX group showed significant increases in COL2α1,HIF1α,NIX,Beclin1,and LC3 Ⅱ/LC3Ⅰ(all P＜0.01)and significant decreases in MMP13,ADAMTS5,NLRP3,GSDMD-N,ASC,IL-18 and p62(all P＜0.01).Compared to the control group,the HX group exhibited significant increases in HIF1α,NIX,Beclin1,and LC3Ⅱ/LC3Ⅰ(all P＜0.01)and decreases in p62,NLRP3,GSDMD-N and IL-18(all P＜0.05).Conclusion Hypoxia may eliminate NLRP3 inflammasome and inhibit chondrocyte pyroptosis through HIF1α/NIX-mediated mitochondrial autophagy,thereby reducing IL-1β-induced chondrocyte injury.

Objective To identify potential drug target genes associated with idiopathic pulmonary fibrosis(IPF)and predict therapeutic candidates using a two-sample Mendelian randomization(MR)approach across the druggable genome.Methods Druggable genome data from the DGIdb database and Finan were integrated to identify overlapping genes.A two-sample MR analysis was performed to infer causal relationships between genes and IPF.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),were conducted to explore biological pathways.Drug-target interactions were predicted via DSigDB database screening,followed by molecular docking simulations to evaluate binding affinities.Results Among the 2588 overlapping druggable genes,thirty exhibited significant causal associations with IPF(P＜0.05).Four hub genes(NOD2,LATS2,LTA,and TCF7L2)were enriched in IPF-related pathways,notably Hippo and TNF signaling.Six potential therapeutics were identified:oxyphenbutazone,moexipril,α-galactosylceramide,GSK429286A,CGP74514A,and JW-7-24-1.Molecular docking confirmed strong binding affinities between these drugs and their targets.Conclusion This study has identified thirty druggable gene targets and six candidate drugs for IPF.The enrichment of hub genes in key pathways and validated drug-target interactions provide insights into IPF therapies.

Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?

Objective:To investigate the dosimetry effect of rotational errors of multi-channel cylinder vaginal applicator of intravaginal irradiation after surgery of endometrial cancer.Methods:A total of 18 patients who underwent surgery of endometrial cancer at Peking Union Medical College Hospital from June to December 2022 were selected.The plans of patients who adopted the treatment of multi-channel cylinder applicator of vagina were retrospectively analyzed,which maintained the same retained mode with clinical plan.The applicator was rotated clockwise by 22.5? and 45.0?,respectively,simulating the rotational errors that occurred in placing the applicator among clinical inter-fractions.And then,the changes of dosimetry of target area and organs at risk(OAR)under two kinds of rotation amplitudes were further analyzed.Results:When the applicator was rotated as 22.5?,the minimum doses to 90%volumes of CTV by 2.03%than that of clinical plan,which was significantly different(t=5.86,P<0.05),and the maximal doses to 2cc of OARs of bladder and rectum respectively increased 2.35%and 2.71%,and the differences of them were statistically significant(t=-3.49,-2.40,P<0.05),respectively.When the applicator was rotated as 45?,the D90 of the target area decreased by 5.75%than that of clinical plan,which was statistically significant(t=14.07,P<0.05).The D2cc values of the bladder and rectum increased respectively by 6.50%and 9.49%than that of clinical plan,which were statistically significant(t=-7.72,-6.9,P<0.05).The differences of the exposed doses of sigmoid colon and small intestine after the applicator was rotated by 22.5? and 45.0? between the plan and original plan were respectively less,which were not statistical significance.Conclusion:The multi-channel cylinder applicator can provide individualized dose distribution in intravaginal irradiation.However,attention should be paid to the placement of the applicator when patients undergo inter-fractional treatment,in order to avoid deviations in the angular alignment from the original plan.This can impact the dosages of the target area and OARs.

Objective:To explore the safety key points of total pancreaticoduodenectomy in the era of vascular resection technology and the important factors affecting rapid postoperative recovery.Methods:The clinical data of 52 patients with pancreatic cancer who underwent total pancreaticoduodenectomy in Beijing Chaoyang Hospital Affiliated to Capital Medical University from November 2014 to September 2022 were retrospectively analyzed, including 34 males and 18 females, aged (62±9). The intraoperative situation, incidence of postoperative complication, postoperative blood glucose control and postoperative survival rate were analyzed.Results:All operations of the 52 patients were successfully completed, including 48 patients underwent total pancreaticoduodenectomy combined with portal vein resection and allograft vascular grafts via artery approach. The portal vein occlusion time was (20±5) min. The incidence of postoperative complications was 28.8% (15/52), including 2 cases of abnormal gastric empty, 2 cases of diarrhea, 2 cases of chylous fistula, 4 cases of abdominal infection, 1 case of gastrointestinal fistula, 3 cases of gastrointestinal bleeding, and 1 case of pulmonary infection. Subcutaneous short-acting insulin injection was used to control blood glucose in the early stage after surgery, short-acting insulin combined with long-acting insulin was used for subcutaneous injection before sleep for diet recovery. All patients did not experience uncontrolled hyperglycemia. The median survival time of 52 patients was 13 months, and the longest follow-up time was 38 months. There were 37 patients died of tumor recurrence, 4 patients died of cardiovascular and cerebrovascular accidents, and 1 patient died of pulmonary infection in the 42 died patients.Conclusions:Total pancreaticoduodenectomy via artery approach can improve the R 0 resection rate in pancreatic cancer patients with vascular invasion, the rate of postoperative complication and mortality has no significant increase. The postoperative blood sugar control is satisfactory and the quality of life is guaranteed.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To evaluate the effective dose, efficacy and safety of remimazolam for induction of general anesthesia in super-elderly patients.Methods:Trial Ⅰ American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, aged ≥80 yr, with body mass index of 18-25 kg/m 2, undergoing elective surgery with general anesthesia in the Zhejiang Provincial People′s Hospital from January to March 2022, were selected. Remimazolam 0.12 mg/kg or propofol 0.8 mg/kg was intravenously injected in the first patient, and the dose of remimazolam or propofol in the next patient was determined by using the modified Dixon′s up-and-down method. The difference between the two successive doses was 0.01 mg/kg for remimazolam and 0.05 mg/kg for propofol. A positive response was defined as achieving an anesthesia depth (BIS value ≤ 65) within 5 min of administration. If the response was positive, the next patient received a lower dose, or conversely if negative, a higher dose was given in the next patient. The 50% effective dose (ED 50) and 90% effective dose (ED 90) of remifentanil and propofol and their 95% confidence intervals ( CIs) were calculated by Probit method. Trial Ⅱ One hundred and forty-six American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ elderly patients of either sex, aged ≥80 yr, with a body mass index of 18-25 mg/kg, scheduled for elective surgery with general anesthesia from April to October 2023 in Zhejiang Provincial People′s Hospital, were selected and divided into 2 groups ( n=73 each) by using a random number table method: remimazolam group (R group) and propofol group (P group). R group was induced with intravenous remimazolam ED 90 and P group was induced with intravenous propofol ED 90, and the injection time was both 30 s. If the BIS value was still greater than 65 at 5 min after administration, remimazolam 0.05 mg/kg was intravenously added each time in R group and propofol 0.5 mg/kg was intravenously added each time in P group until the patient′s BIS value ≤65. The success of anesthesia induction, time for successful induction of anesthesia and rescue sedation were recorded. The occurrence of intraoperative injection pain, hypertension, hypotension, bradycardia, hypoxemia, intraoperative awareness and postoperative delirium, nausea and vomiting was also recorded. Results:Trial Ⅰ The ED 50 (95% CI) of remimazolam was 0.148 (0.139-0.157) mg/kg, and the ED 90 (95% CI) was 0.160 (0.153-0.202) mg/kg; the ED 50 (95% CI) of propofol was 0.824 (0.726-0.983) mg/kg, and the ED 90 (95% CI) was 0.916 (0.860-2.472) mg/kg. Trial Ⅱ Compared with group P, the time for successful induction of anesthesia was significantly prolonged, the incidence of intraoperative injection pain and hypotension was decreased ( P<0.05), and no significant change was found in the success rate of anesthesia induction, rate of rescue sedation, intraoperative hypertension, bradycardia, hypoxemia, postoperative delirium, and nausea and vomiting in group R ( P>0.05). Conclusions:The ED 50 and ED 90 of remimazolam for induction of general anesthesia are 0.148 and 0.160 mg/kg, respectively, in super-elderly patients. Compared to propofol, remimazolam has a slightly longer onset time, but it is safer when used for induction of general anesthesia in super-elderly patients.

Objective To investigate the efficacy of single-use flexible ureteroscopes combined with flexible tip negative pressure suction sheath in the primary treatment of upper urinary tract stones. Methods A total of 236 patients with upper urinary tract stones were selected as study subjects. Through retrospective analysis, the patients were divided into study group (n=118) and control group (n=118). The study group was treated with single-use flexible ureteroscopes combined with flexible tip negative pressure suction sheath, while the control group received treatment with single-use flexible ureter oscopes combined with conventional sheath. The postoperative pain level [Visual Analogue Scale (VAS)], inflammatory markers, stress indicators, renal function parameters, complication rates and stone clearance rates were compared between the two groups. Results On the first, second, and third postoperative day, the VAS scores in the control group were significantly higher than those in the study group (P < 0.05). At 1 d after surgery, the levels of C-reactive protein, interleukin-6, procalcitonin, norepinephrine and cortisol in the study group were significantly lower than those in the control group (P < 0.05). Additionally, on the first postoperative day, the levels of urea nitrogen, serum creatinine, uric acid and cystatin C in the study group were significantly higher than those in the control group (P < 0.05). The overall complication rate in the study group was 14.4%, which was significantly lower than 27.1% in the control group (P < 0.05). The postoperative stone clearance rate in the study group was 98.3%, which was significantly higher than 88.1% in the control group (P < 0.05). Conclusion The combination of single-use flexible ureteroscopes and flexible tip negative pressure suction sheath exhibits superior efficacy in the primary treatment of upper urinary tract stones. This approach can enhance stone clearance rates, reduces complication rates, alleviate postoperative pain and inflammatory responses, and promotes renal function recovery.