Objective:The study investigated the full-time Clinical Research Coordinators (CRCs) working in hospitals on their current working situation and explored affecting factors to provide suggestions for a professional and systemic clinical research workforce establishment in municipal medical institutions.Methods:A questionnaire survey was designed for CRCs in municipal hospitals in Shanghai, descriptive and one-way cross-tabulation analysis were conducted, using t-test for continuous numerical variables, rank-sum test for count variables and chi-square test for categorical variables.Results:Totaling 177 CRCs in 9 municipal hospitals in Shanghai answered the questionnaire. The average age of the respondents was 28.56±7.299 years old. Their professional background was mainly nursing and pharmacy (139/177, 87.53%), and bachelor degree (114/177, 64.41%). Averagely worked 2.50±1.632 years, the average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. The CRCs employed by hospitals mainly undertook Investigator-Initiated clinical Trial/Research projects (IITs) (26/36, 72.22%), while the CRCs employed by SMO companies mainly undertook Industry-Sponsored Clinical Trial (IST) projects (96/141, 68.09%). 85.88% (152/117) of CRCs held GCP certificates valid within three years, and the proportion of CRCs employed by hospitals held GCP certificates was lower than that of SMO companies ( P<0.05). Among the CRCs employed by hospitals, 23 (63.89%) said they had no position or were not clear about their position; The CRCs in SMO companies were mainly primary and intermediate (χ 2=84.119, P<0.05). The average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. Conclusions:With the development of clinical research, the full-time specialized CRCs in medical institutions mainly have 2 sources: from SMO/CRO companies or self-employment by medical institutions. In general, there are still problems in the CRC talent team as unclear entry standards, insufficient, lack career positioning planning, large mobility, imperfect training system, and imperfect promotion mechanism. It is suggested to unify occupational access standards and set specialty in colleges or universities. Strengthen post-service education and training system, establish multi-party collaborative training mechanism, standardize the assessment and evaluation, improve the job title promotion system, to promote the rapid development of CRC team.

Objectives:To investigate the protective effect of nicotinamide adenine dinucleotide (NAD?) against noise-induced cochlear damage and preliminarily explore its underlying transcriptional and metabolic regulatory mechanisms.Methods:During the study period (January 2023-February 2025), an oxidative stress model was established using House Ear Institute-organ of Corti 1 (HEI-OC1) cells, and cell viability was assessed using the Cell Counting Kit-8 (CCK8) assay. Flow cytometry was employed to analyze cell apoptosis. A mouse model of noise-induced hearing loss was developed, and the mice were divided into three groups: a noise-exposed saline group, a noise-exposed NAD? intervention group, and a noise-free control group. Hearing protection effects were evaluated by auditory brainstem response (ABR) and immunofluorescence. Metabolomics and transcriptomics were used to analyze the regulatory effects of NAD +on transcription and metabolism in mouse cochlea. Enzyme-linked immunosorbent assay, quantitative real-time PCR, and western blot were used to verify the differential transcription and metabolic molecules and their functions. Data were statistically analyzed with GraphPad Prism 9.3.0. Results:NAD +at concentrations ranging from 10-80 μM effectively restored cell viability and reduced apoptosis induced by H?O? in HEI-OC1 cells. NAD? intervention significantly improved 16-32 kHz ABR thresholds after noise exposure ( P<0.05), reduced outer hair cell loss rates ( P<0.05), and attenuated ribbon synapse damage ( P<0.000 1). Metabolomics analysis revealed a significant downregulation in the glycerophospholipid metabolism pathway, with decreased levels of lysophosphatidic acid (LPA) and its related metabolites. ELISA results showed that LPA levels in the NAD? intervention group were significantly lower ( P<0.05). LPA inhibitor (ATX inhibitor 1) exhibited a cell protective effect similar to that of NAD?. Transcriptomics analysis indicated a significant upregulation of key genes related to potassium ion channels, such as Kcnq4. qPCR and Western blot further confirmed the significant upregulation of Kcnq4 and its encoded protein in the NAD? intervention group ( P<0.05). In the presence of the KCNQ4 inhibitor (ML252), the protective effect of NAD? was inhibited. Conclusions:NAD? exerts effective protective effects against noise-induced cochlear injury. Its protective mechanism may be closely related to the inhibition of LPA metabolic pathway and the up-regulation of KCNQ4 channel function.

To explore the scoring level and related factors of autoimmune disease-related skin ulcers by collecting data from multiple centers, and to provide ideas and references for targeted intervention measures and management plans for clinical medical and nursing staff.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

Objective:The study investigated the full-time Clinical Research Coordinators (CRCs) working in hospitals on their current working situation and explored affecting factors to provide suggestions for a professional and systemic clinical research workforce establishment in municipal medical institutions.Methods:A questionnaire survey was designed for CRCs in municipal hospitals in Shanghai, descriptive and one-way cross-tabulation analysis were conducted, using t-test for continuous numerical variables, rank-sum test for count variables and chi-square test for categorical variables.Results:Totaling 177 CRCs in 9 municipal hospitals in Shanghai answered the questionnaire. The average age of the respondents was 28.56±7.299 years old. Their professional background was mainly nursing and pharmacy (139/177, 87.53%), and bachelor degree (114/177, 64.41%). Averagely worked 2.50±1.632 years, the average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. The CRCs employed by hospitals mainly undertook Investigator-Initiated clinical Trial/Research projects (IITs) (26/36, 72.22%), while the CRCs employed by SMO companies mainly undertook Industry-Sponsored Clinical Trial (IST) projects (96/141, 68.09%). 85.88% (152/117) of CRCs held GCP certificates valid within three years, and the proportion of CRCs employed by hospitals held GCP certificates was lower than that of SMO companies ( P<0.05). Among the CRCs employed by hospitals, 23 (63.89%) said they had no position or were not clear about their position; The CRCs in SMO companies were mainly primary and intermediate (χ 2=84.119, P<0.05). The average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. Conclusions:With the development of clinical research, the full-time specialized CRCs in medical institutions mainly have 2 sources: from SMO/CRO companies or self-employment by medical institutions. In general, there are still problems in the CRC talent team as unclear entry standards, insufficient, lack career positioning planning, large mobility, imperfect training system, and imperfect promotion mechanism. It is suggested to unify occupational access standards and set specialty in colleges or universities. Strengthen post-service education and training system, establish multi-party collaborative training mechanism, standardize the assessment and evaluation, improve the job title promotion system, to promote the rapid development of CRC team.

Objectives:To investigate the protective effect of nicotinamide adenine dinucleotide (NAD?) against noise-induced cochlear damage and preliminarily explore its underlying transcriptional and metabolic regulatory mechanisms.Methods:During the study period (January 2023-February 2025), an oxidative stress model was established using House Ear Institute-organ of Corti 1 (HEI-OC1) cells, and cell viability was assessed using the Cell Counting Kit-8 (CCK8) assay. Flow cytometry was employed to analyze cell apoptosis. A mouse model of noise-induced hearing loss was developed, and the mice were divided into three groups: a noise-exposed saline group, a noise-exposed NAD? intervention group, and a noise-free control group. Hearing protection effects were evaluated by auditory brainstem response (ABR) and immunofluorescence. Metabolomics and transcriptomics were used to analyze the regulatory effects of NAD +on transcription and metabolism in mouse cochlea. Enzyme-linked immunosorbent assay, quantitative real-time PCR, and western blot were used to verify the differential transcription and metabolic molecules and their functions. Data were statistically analyzed with GraphPad Prism 9.3.0. Results:NAD +at concentrations ranging from 10-80 μM effectively restored cell viability and reduced apoptosis induced by H?O? in HEI-OC1 cells. NAD? intervention significantly improved 16-32 kHz ABR thresholds after noise exposure ( P<0.05), reduced outer hair cell loss rates ( P<0.05), and attenuated ribbon synapse damage ( P<0.000 1). Metabolomics analysis revealed a significant downregulation in the glycerophospholipid metabolism pathway, with decreased levels of lysophosphatidic acid (LPA) and its related metabolites. ELISA results showed that LPA levels in the NAD? intervention group were significantly lower ( P<0.05). LPA inhibitor (ATX inhibitor 1) exhibited a cell protective effect similar to that of NAD?. Transcriptomics analysis indicated a significant upregulation of key genes related to potassium ion channels, such as Kcnq4. qPCR and Western blot further confirmed the significant upregulation of Kcnq4 and its encoded protein in the NAD? intervention group ( P<0.05). In the presence of the KCNQ4 inhibitor (ML252), the protective effect of NAD? was inhibited. Conclusions:NAD? exerts effective protective effects against noise-induced cochlear injury. Its protective mechanism may be closely related to the inhibition of LPA metabolic pathway and the up-regulation of KCNQ4 channel function.

Objective : To analyze the trends in mortality and life lost due to bladder cancer in Suzhou City, Jiangsu Province from 2003 to 2022, so as to provide the reference for prevention and treatment strategy of bladder cancer. Methods: The data of bladder cancer death in Suzhou City from 2003 to 2022 were collected through Suzhou Residents' Death Registration System, including age, gender, date of death and underlying cause of death. The crude mortality, standardized mortality, years of potential life lost (PYLL), standardized years of potential life lost (SPYLL), years of potential life lost rate (PYLLR), standardized years of potential life lost rate (SPYLLR) and average years of life lost (AYLL) were calculated. The average annual percent change (AAPC) was used to analyze the trends in bladder cancer death and life lost. Results: Totally 2 978 deaths occurred due to bladder cancer in Suzhou City from 2003 to 2022. The crude mortality was 2.22/105, which appeared a tendency towards a rise (AAPC=4.271%, P<0.05). The standardized mortality was 0.91/105, which appeared no significant changing trend (P>0.05). The standardized mortality was 1.58/105 in males and 0.37/105 in females, which appeared no significant tendency in males (P>0.05) and appeared a tendency towards a decline in females (AAPC=-2.331%, P<0.05). The age-specific crude mortality was low among people who aged under 45 years, began to rise among people aged over 45 years and peaked among people aged 60 years and older. The crude mortality of bladder cancer in males aged 60 years and older showed an increasing trend (AAPC=2.864%, P<0.05), but there was no significant tendency in females aged 60 years and older (P>0.05). The PYLL, SPYLL, PYLLR, SPYLLR and AYLL of bladder cancer were 5 020.00 person-years, 2 945.14 person-years, 0.04‰, 0.03‰ and 9.07 years per person. SPYLL, SPYLLR and AYLL showed an decreasing trend (AAPC=-2.867%, -3.321%, -3.738%, P<0.05). Conclusions The mortality of bladder cancer in Suzhou City appeared a tendency towards a rise from 2003 to 2022. The PYLL appeared a downward trend. Males aged 60 years and older are the key groups for the prevention and control of bladder cancer.

Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

The difference in the crystal form of the drug leads to different solubility and stability,affecting drug's the clinical efficacy and bioavailability.Therefore,in recent years,drug crystal forms have received more and more attention from researchers.By reviewing and sorting out relevant literature,this paper summarizes the research progress of drug crystallization theory in recent years from the aspects of influencing factors of drug crystal form,identification and control of drug crystal form,drug crystal form evaluation methods,and applications,aiming to provide a reference for drug crystal form control and process screening.