Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Objective:To investigate the clinical features of 17q12 microdeletion cases before and after delivery, and provide a reference for prenatal diagnosis and genetic counseling.Methods:A retrospective analysis was conducted on five fetuses diagnosed with 17q12 microdeletion by single nucleotide polymorphism array in Quanzhou Women's and Children's Hospital between April 2020 and June 2023. Clinical data including prenatal ultrasonography findings, genetic causes, parental clinical features, and postnatal outcomes were summarized and analyzed using descriptive statistical analysis.Results:The five fetuses had normal results of karyotype analysis of amniotic fluid, but carried a microdeletion of 1.4 to 1.8 Mb in the 17q12 region of the chromosome, involving 20 genes listed in the Online Mendelian Inheritance in Man database. Pedigree verification was performed on all five cases and the results indicated one maternally inherited case with the mother having polycystic kidneys complicated by left hydronephrosis, one de novo case, and three paternally inherited cases with one father having multiple cysts in both kidneys and two fathers showing no abnormalities. Multiple abnormalities were found in the five fetuses by prenatal ultrasonography, including enhanced renal parenchymal echogenicity in four cases and pyelectasis in one case. Two cases chose to terminate the pregnancies, while the other three continued the pregnancies to full term. Postnatal follow-ups showed that one case was normal in growth and development with no abnormalities by renal ultrasound; one case developed polycystic kidney; one case with normal renal ultrasound findings had a speech disorder and symptoms of suspected autism at the age of three. Conclusions:The main manifestation of 17q12 microdeletion is enhanced renal parenchymal echogenicity in the fetal stage and postnatal polycystic kidney. In prenatally diagnosed cases, pedigree verification is necessary as an objective and scientific genetic counseling is helpful in pregnancy decision-making.

Objective:To retrospectively compare the clinical efficacy of two PDE3 inhibitors, oplinone and Milrinone, in order to evaluate which drug has better effects on the improvement of cardiac function, protection of renal function and adverse effects of arrhythmia.Methods:A total of 41 neonates with congenital heart disease after biventricular treatment under cardiopulmonary bypass in the Department of Cardiothoracic Surgery at Soochow University Children's Hospital during 2018-2022 were collected. The experimental group was divided into two groups: Oprilinone(25 cases) and Milinone(16 cases). A retrospective study was conducted on the incidence of renal function, cardiac function improvement and arrhythmia in the children.Results:On the first day after operation, EF in both groups decreased significantly compared with that before operation( P<0.01); On day 4 after surgery, EF in the oprilinone group was significantly higher than that on day 1 after surgery( P<0.01), Milrinone group was slightly higher than that on day 1 after surgery( P<0.05), and EF in oprilinone group was significantly higher than that in Milinone group during the same period( P<0.01); EF in Milinone group continued to increase on day 7 compared with day 4( P<0.01), but there was no significant difference between the two groups. Long-term follow-up showed that there was no significant difference in EF value in the oprilinone intervention group on day 7 after surgery( P<0.05), and the long-term EF in Milinone group was higher than that at 7 days after surgery( P<0.05). The creatinine level in the oprinone intervention group continued to decrease on the 4th and 7th day after surgery( P<0.01; P<0.05); The creatinine level of Milinone group on day 4 after surgery was significantly lower than that on day 1 after surgery( P<0.01), the decrease was not significant on the 7th day after surgery compared with the 4th day after surgery; The creatinine level in the oprilinone group was lower than that in the Milrinone group on day 7 after surgery( P<0.05). The rate of arrhythmia in children was slightly decreased in the intervention group of olplinone. There was no change in the Milinone group. Conclusion:Oplinone improved cardiac function better than Milrinone, and the recovery time to normal cardiac function was shorter. In terms of renal function protection, oplinone was stronger than Milrinone, and the protective effect of oplinone on kidney lasted longer. No significant abnormalities were found with respect to adverse reactions, such as the incidence of arrhythmia.

Objective : To investigate the influence and molecular mechanism of hypoxia-inducing factor-1 α( HIF- 1 α) gene silencing combined with methyl selenenic acid (MSA) on cervical cancer cell proliferation，apoptosis and cell migration． Methods : HeLa cells were transfected with HIF-1 interference RNA and negative control RNA．Af- ter transfection for 48 h，cells were stimulated with MSA for 24 h，and cell proliferation was determined by CCK-8 assay and colony formation．Apoptosis was determined by flow cytometry combined with Annexin V-FITC / PI．The expression levels of HIF-1α , Bcl-2 ，and E-cadherin were detected by Western blot assay． Cell migration ability was determined by Transwell assay. RNA-seq analysis was used to investigate the differentially expressed genes and differential signaling pathways. Results : Compared with the control group，interfering with HIF-1α combined with MSA significantly inhibited cell proliferation (P ＜0．01) ．Flow cytometry results showed that the combined drug group significantly induced apoptosis．Transwell results showed that interfering with HIF-1α combined with MSA inhibited HeLa cell migration．Compared with the control group，interfering with HIF-1α combined with MSA down- regulated the expression of Bcl-2 and up-regulated the expression of E-cadherin. RNA-sequencing combined with signal pathway enrichment results showed that the expression of apoptotic signal pathway and downstream genes was inhibited． Conclusion HIF-1α gene silencing combined with MSA can synergically inhibit the proliferation and induce apoptosis of cervical cancer cells，and its regulatory mechanism may be related to the expression of Bcl-2 family proteins and the inhibition of p53 signaling pathway.

OBJECTIVE： To provide reference for reasonable selection of tyrosine kinase inhibitors （TKI） in chronic myeloid leukemia （CML） patients with BCR-ABL35INS mutation. METHODS： Using “BCR-ABL insertional mutation” “ABL1 35ins mutation” “BCR-ABL c.1423_1424ins35” “ABL1 p.C475Tyrfs*11” as keywords， retrieved from CNKI， Wanfang database， Medline and COSMIC database， BCR-ABL35INS mutation CML patients were summarized and analyzed in respects of general information and treatment （treatment plan， patient compliance and drug withdrawal）， therapeutic effect （molecular biological mitigation and disease progress） and safety data （ADR） during 2007-2018. RESULTS： Totally 9 related literatures were included， involving 70 patients with BCR-ABL35INS mutation， all of them were foreign cases. Among them， 39 cases were male and 31 cases were female， with a median age of 49.2 years. The median time from the diagnosis of CML to the detection of BCR-ABL35INS mutation was 19 months. After detecting gene mutation， 39 cases were treated with imatinib （initial dose of 400 mg， po， once a day）， and molecular biological remission was achieved in 5 patients （12.9％）； 15 cases （38.5％） had molecular biological response but had disease progression； 8 patients （20.5％） had no response. Seventeen patients were treated with dasatinib （100 mg， po， once a day or 2 divided dose）， and 8 cases （47.1％） achieved molecular biological response. Twenty-one patients were treated with nilotinib （400 mg， po， 2 divided dose）， and 3 patients （14.3％） achieved molecular biological response； 2 patients achieved molecular biological response， but the disease progressed. Seven， three and seven of these patients stopped taking drugs due to adverse reactions， accounting for 17.9％， 17.6％ and 33.3％ respectively. All the ADRs were classified as grade 3-4 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events， and most of them were hematological toxicity. CONCLUSIONS： CML patients with BCR-ABL35INS mutation are less likely to achieve molecular response on imatinib therapy but are more sensitive to dashatinib. In the course of treatment， we should strengthen the monitoring of blood system and other related indicators to ensure the safety and effectiveness of drug use.

Through the systematic analysis on the primo vascular system (PVS) in recent years, we believe that in recent years, more and more studies have indicated that PVS is distributed in reticulate structure in every part of body, such as vessels, lymphangions, nerves, brain, spinal cords and internal organs, and it contains a large amount of immunocytes and has involved in the physiological or pathological process of the immunity and circulation in the body. There are the evidences to prove that in morphology and cytobiology. But, nowadays, there is no way to explain its effect characters. On the basis of the study on living matter characteristics, a breakthrough is possibly made through the systematic cooperation even though it is the difficulty to detect the life function effect. It is especially displayed in the substantial study on meridian points. Hence, the study on the law of meridian point effects on the basis of clinical practice has to be focused on in the substantial study on meridian points.

OBJECTIVE:To systematically review the effect of CYP2C19 genetic polymorphism on lansoprazole pharmacoki-netics,and provide evidence-based reference for clinical individualized medication of lansoprazole. METHODS:Retrieved from PubMed,EMBase,Web of science,Cochrane Library and CJFD,retrospective studies about the effect of CYP2C19 genetic poly-morphism on lansoprazole pharmacokinetics were collected,Meta-analysis was performed by Rev Man 5.2 software after data ex-tract and quality evaluation. RESULTS:Totally 11 retrospective studies were included,involving 200 patients. The gene type in-cluded homozygote express metabolizers (EM),heterozygous express metabolizers (HEM) and slow metabolizers (PM). Results of Meta-analysis showed CYP2C19 polymorphism significantly affected cmax,AUC,t1/2,tmax and CL/F. The cmax and AUC in group PM were higher than group HEM and group EM;CL/F in group EM was higher than group HEM and group PM;t1/2 in group PM was higher than group HEM and group EM,while there was no significant difference in the t1/2 between group HEM and group EM;tmax in HEM and group PM were higher than group EM,while there was no significant difference in the tmax between group PM and group HEM. CONCLUSIONS:CYP2C19 genetic polymorphism shows obvious effect on lansoprazole pharmacokinetics, which is the key factor for causing efficacy of lansoprazole and individual differences among adverse reactions,and clinic should take into account individualized dose regimen of lansoprazole.

OBJECTIVE:To investigate the way to provide suitable pharmacecaical care for antineophastic drug-induced ADR by clinical pharmacists. METHODS:For one case of 5-FU chemotherapy-induced neutropenia associated with fever and diarrhea, clinical pharmacists provided advices on antibacterial treatment,including imipenem/cilastatin 0.5 g,q6 h,ivgtt;norvancomycin 0.4 g,q6 h,po;levofloxacin 0.4 g,qd,ivgtt;loperamide with initial dose of 4 mg for anti-diarrheal medication,maintaining at 2 mg,q4 h. RESULTS:After 22 days of appropriate antibacterial and anti-diarrheal treatment,the patient's body temperature and he-mogram returned to normal,diarrhea stopped and β-HCG decreased to 61.58 U/L;then the patient was discharged from hospital. CONCLUSIONS:It is beneficial to optimize chemotherapy plan and ADR disposal,and ensure the safety of the treatment that clini-cal pharmacists assist physicans to optimize therapy plan and provide pharmaceutical care.

OBJECTIVE:To systematically evaluate the efficacy and safety of simvastatin vs. pravastatin in the treatment of hy-perlipidemia,and provide evidence-based reference for the clinical treatment. METHODS:PubMed,Medline,EMBase,Cochrane Library and CJFD were retrieved to collect the randomized controlled trial(RCT)of efficacy and safety of simvastatin(test group) and pravastatin (control group) in the treatment of hyperlipidemia. The methodological quality of included studies was evaluated. The Rev Man 5.2 software was chosen for data analysis. RESULTS:14 RCT involving 1 019 patients were included. Meta-analysis showed that simvastatin had more significant effect in the decreasing of TC [MD=-0.34,95%CI(-0.52,-0.16),P<0.001] and LDL-C[MD=-0.31,95%CI(-0.45,-0.17),P<0.001] than pravastatin;and simvastatin and pravastatin had the similar effect in TG[MD=-0.06,95%CI(-0.18,0.05),P=0.28)] and HDL-C[MD=0.00,95%CI(-0.04,0.04),P=0.85]. Adverse drug reaction rate results showed they were similar[OR=0.70,95%CI(0.36,1.39),P=0.31]. CONCLUSIONS:Simvastatin is more effective in lipid-lowering than pravastatin with similar safety. Due to the limited number and low quality of included studies,it remains to be further verified with more reasonably designed,multi-center and large-sample studies.

This article manages to find some methods to improve students' innovative spirit and ability with some pharmaceutical teaching practice