Objective To explore the effects of HPV16 E6 on genes and signaling pathways in cervical epithelial cells and to screen genes associated with oncogenic transformation.Methods HUCEC models infected with HPV16 E6 were constructed,and transcriptome sequencing was performed to screen for differentially expressed genes(DEGs),which were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment to analyze the differential signaling pathways.RT-qPCR was used to validate major differentially down-regulated expressed genes.After predicting the major differentially expressed proteins by molecular docking analysis,the expression of major differential genes in HUCEC cell model was verified by RT-qPCR and Western blotting.In addition,RT-qPCR and Western blotting were used to further verify the expression of major differential genes in cervical cancer cell lines,SiHa and CaSki.Results A total of 55 genes with more than two-fold differential expression were screened.The results centering on down-regulated genes showed that the negatively regulated differential gene was mainly enriched in redox processes;KEGG enrichment analysis revealed that it was mainly associated with carbohydrate metabolism and cancer.RT-qPCR results showed that the down-regulated differential expression trends of the selected 10 genes were basically consistent with the sequencing results.Molecular docking analysis predicted an interaction between DHRS2 and HPV16 E6,and RT-qPCR and Western blotting confirmed that HPV16 E6 down-regulated DHRS2 mRNA(P＜0.01)and protein(P＜0.05)and ETV5 protein expression(P＜0.01).In SiHa and CaSki cells,compared with the control group,the mRNA and protein expression of DHRS2 was downregulated and positively correlated with the trend of P53 protein expression(P＜0.05).Conclusion HPV16 E6 can mediate oncogenic transformation of cervical cells and promote cervical carcinogenesis through downregulating DHRS2 expression.

Objective:To establish an animal model of trans-sutural distraction osteogenesis in SD rats.Methods:A self-designed V-shaped distraction device(distractor)was fabricated with the traction force(N)of 0,1.3,2.2,3.0,4.3 and 5.0 corresponding to the distraction length(mm)of 5,4,3,2,1 and 0 respectively,meeting the trans-sutural distraction osteogenesis requirements in skull of 5-week-old SD rats.The distractor was plased into the sagittal suture of 12 SD rats.Continuous sampling was conducted 1,3,5 and 7 days respectively(n=3)after operation.The tissue changes in the trans-sutural distraction area were observed by HE and Masson's trichrome staining.Inflammation levels were determined using Arg-1 immunofluorescence staining.The early angiogenesis was clarified through co-staining with CD31 and EMCN.Results:A stable trans-sutural distraction osteogenesis model was estab-lished,5 mm distraction osteogenesis width was observed completely within 7 days of distraction.Significant new bone formation was observed at 7 days after operation.Arg-1 expression increased and was concentrated at the bone margins,overlapping with the areas of new bone formation.EMCN expression gradually decreased,and by day 7 CD31 was predominant,indicating the basic maturation of blood vessels.Conclusion:This study successfully constructed a stable and effective trans-sutural distraction osteogenesis animal model,and provides an experimental basis for the investigation of its early continuous histological changes.

【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.

OBJECTIVE In the context of the era of innovation and entrepreneurship, the training model of pharmaceutical talents is facing challenges. In order to cultivate overall development of pharmaceutical innovative talents, an in-depth research is carried out from multiple perspectives such as education orientation, education mode and education team. METHODS The research systematically analyzed the concept, system, orientation, channels, plan and cooperation of pharmaceutical talent training to build a new cultivation mechanism which adapts to the national strategic adjustments and social situation changes. RESULTS The research summarized the ideas and formulated a model for cultivating innovative application-oriented pharmaceutical talents which was guided by ideological and political education, oriented towards real issues in the industrial, scientific, and clinical sectors. It emphasized multi-chain collaboration, integrating high-quality resources to promote the enhancement of original innovation capabilities. CONCLUSION The research not only provides experience for the training of pharmaceutical innovative talents in the College of Pharmaceutical Sciences of Zhejiang University, but also provides references for the training of pharmaceutical talents in other universities in China.

Objective:To observe the effect of disposable flexible ureteroscopy and laser lithotripsy combined with flexible ureteroscope sheath implantation in the treatment of patients with renal calculi.Methods:Sixty patients with kidney calculi treated by disposable flexible ureteroscopy and laser lithotripsy combined with flexible ureteroscope sheath implantation in the Second Affiliated Hospital of Xi′an Medical College from February 2021 to January 2024 were retrospectively selected as the observation group, matched according to age (±5 years) and gender factors, according to the random number table method, 60 patients with kidney calculi who were treated with disposable ureteroscopy combined with laser lithotripsy at the same time were selected as the control group. The amount of intraoperative blood loss, operation time and hospital stay were recorded and compared between the two groups. Serum renal function parameters urea nitrogen and creatinine levels were measured by automatic biochemical analyzer before and 3 days after surgery, and serum inflammatory factor C-reactive protein (CRP) and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay (ELISA). The incidence of complications was recorded and compared between the two groups. Measurement data were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups. The count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Results:The intraoperative blood loss, operation time and hospital stay in the observation group [(23.2±5.9) mL, (98.8±8.5) min, (4.2±1.0) d, respectively] were all lower than those in the control group [(27.3±6.5) mL, (112.5±9.8) min, (4.7±1.3) d, respectively], the differences were statistically significant ( P<0.05). The success rate of stone removal in the observation group was 100.00% (60/60), higher than that in the control group (81.67%, 49/60), and the difference was statistically significant ( χ2=10.01, P=0.002). 3 days after surgery, the levels of serum urea nitrogen, creatinine, CRP and IL-6 in the observation group [(7.04±1.24) mmol/L, (73.21±6.87) μmol/L, (15.83±2.57) mg/L, (10.52±1.02) ng/L] were lower than those in the control group [(7.63±1.32) mmol/L, (78.59±7.52) μmol/L, (21.32±3.22) mg/L, (15.47±1.35) ng/L], the difference were statistically significant ( P<0.05). The incidence of postoperative complications in the observation group (3.33%) was lower than that in the control group (13.33%), and the difference was statistically significant ( χ2=3.93, P=0.048). Conclusion:Disposable flexible ureteroscopy and laser lithotripsy combined with flexible ureteroscope sheath implantation in the treatment of patients with renal calculi can improve the protection of renal function, improve the stone removal rate of patients, reduce postoperative blood loss and complications, shorten the operation time and hospital stay, improve inflammatory response, and have good clinical efficacy.

For the treatment of atrial fibrillation,Professor WU Wei innovatively put forward the theory of heart-blood-vessels trinity and the theory of stasis-toxin causing palpitation.It is believed that atrial fibrillation is caused by stasis and toxin,and affects the heart,blood and vessels.The core pathogenesis of atrial fibrillation is due to qi stagnation,blood stasis and toxin.The treatment for atrial fibrillation should be closely based on the pathogenesis,the therapeutic principles of treating from the perspective of stasis and together by removing toxin gradually is advocated.And the therapy of regulating qi,activating blood and removing stasis is also the way to remove toxin.The medication is based on the modified Taoren Honghua Decoction,which is mainly composed of Persicae Semen,Carthami Flos,Chuanxiong Rhizoma,Corydalis Rhizoma,Rehmanniae Radix,Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix et Rhizoma,Jujubae Fructus,Puerariae Lobatae Radix,Nardostachyos Radix et Rhizoma,Ostreae Concha,Poria,and Polygonati Odorati Rhizoma.According to the characteristics of Lingnan climate and atrial fibrillation mostly being easy to affect the emotions,the pungent drugs in the prescription are usually removed,and the specific herbal pair of Puerariae Lobatae Radix-Nardostachyos Radix et Rhizoma is added to remove toxin according to the differentiation of disease.Moreover,for the treatment of atrial fibrillation,Professor WU Wei also adopts traditional Chinese medicine(TCM)external treatment such as foot bath,acupuncture and moxibustion,and physical-breathing exercise as well as health-care methods for comprehensive regulation,relieving the toxin and restoring the original qi.During the treatment atrial fibrillation,Professor WU Wei follows the principle of precise intervention and comprehensive regulation with Chinese medicine,so as to achieve the purpose of eliminating symptoms,restoring sinus rhythm and improving physical constitution.The thoughts of Professor WU Wei for the syndrome differentiation and treatment of atrial fibrillation will provide reference for the treatment of atrial fibrillation with TCM.

Objective:To summarize and visualize the status quo,future hotspots and development trend of ED-related resear-ches in China through bibliometric analysis.Methods:We searched the Web of Science Core Collection(WOSCC)and the database of Chinese National Knowledge Infrastructure(CNKI)for ED-related studies published in China from January 1,2010 to August 14,2023.Using the CiteSpace and VOSviewer softwares,we bibliometrically analyzed and visualized the related journals,regions,institu-tions,authors,key words,co-citations and other indexes of the identified studies.Results:A total of 2,465 ED-related studies were retrieved,with an increasing number of publications year by year,relatively more in the southeast region,with Sun Yat-sen University ranking the first in the number of published articles(n=169),LIU Jihong(n=73),WANG Tao(n=71)and JIANG Rui(n=49)as the top three prolific core authors.The first two Chinese journals with the most ED-related publications were Chinese Journal of Andrology(n=320)and Journal of Sexual Medicine(n=128),and the latter was also the mostly cited(n=5 060).Keyword co-occurrence analysis showed that the highest-frequency Chinese terms included impotence,anxiety,andrology,expert consensus,ex-perience of famous doctors,acupuncture,Earthworm protein(Chinese)and hypertension,and the English terms included erectile dys-function,apoptosis,inflammation,fibrosis,risk and women.Conclusion:Recent years have wit-nessed a rapid development in ED-related studies in China,with the risk factors and patho-genic mechanisms of ED as hot topics.PDE5 inhibitors and adipose-derived stem cells for the treatment of ED have attracted long and continuous attention and will remain an important target of future research.

Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe.We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE