With the rapid development of human genomics technologies and their clinical applications， relevant ethical issues have induced complex ethical governance challenges. These challenges mainly manifest in the dilemma of reconstructing a new social contract under data open sharing， the moral conflict between the collective nature of group data and individual benefits， the problem of structural inequality under precision medicine， the risk of imbalance between costs and benefits， the dilemma of genetic modification from a eugenic perspective， and the issue of proxy consent and privacy protection. International governance practices indicate that these challenges can be addressed to some extent by improving legislation， issuing initiatives， strengthening the functions of ethics committees and corresponding institutions， and focusing on the ethicality of research projects. However， issues such as legal lag and insufficient binding force of initiatives still exist. Meanwhile， although China’s ethical governance work has made continuous progress in top-level design， international exchanges and theoretical research， specialized legislation and cross-subject collaboration mechanisms still necessitate improvement. A systematic ethical governance framework requires establishing a pre-regulatory system， refining ethical review， and promoting specialized legislation and case approval systems. It is also vital to improve genomic data governance， refine cloud platform management mechanisms， and promote hierarchical governance of the data. Furthermore， it is crucial to clarify the responsibilities of the scientific research community， standardize ethical review， strengthen public communication， and build a moral community with the collaborative cooperation of the government， medical and healthcare institutions and their technical personnel， the public， and research subjects. Through the construction of an ethical governance system for human genomics research， this ensures that genomics technologies benefit humanity without transgressing ethical boundaries， thereby achieving the safety， fairness， and sustainability of their research and application.

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Objective:To explore the impact of self-disclosure on demoralization syndrome in patients with permanent enterostomy for colorectal cancer, so as to provide reference for clinical nursing interventions for those patients.Methods:From January to May 2023, convenience sampling was used to select 207 patients with permanent enterostomy for colocrctal cancer of the Wound Ostomy Clinic of Laoshan Campus of the Affiliated Hospital of Qingdao University as the research subjects. A survey was conducted on patients using the General Information Questionnaire, Distress Disclosure Index, Social Support Rating Scale, and the Demoralization Scale Mandarin Version.Results:Among 207 patients with permanent enterostomy for colorectal cancer, the scores of self-disclosure, social support, and demoralization syndrome were 35.00 (26.00, 47.00) , 32.00 (26.00, 39.00) , and 35.00 (23.00, 47.00) , respectively. A total of 128 patients (61.8%) were in moderate demoralization, and 37 patients (17.9%) were in severe demoralization. Multiple linear regression analysis showed that place of residence, self-care of stoma, self-disclosure, and social support were the influencing factors for demoralization syndrome in patients with permanent enterostomy for colorectal cancer ( P<0.05) . Conclusions:Patients with permanent enterostomy for colorectal cancer have a high overall score of demoralization syndrome, and a high proportion of patients with moderate to severe demoralization. Medical and nursing staff should focus on patients in remote rural areas and those with poor self-care abilities to stomas, develop targeted intervention measures to improve patients' negative emotions, enhance their self-disclosure, and pay attention to strengthening social support to relieve their demoralization syndrome, thereby improving their quality of life.

Objective:To learn about the age, period, birth cohort characteristics, and incidence trends of hemorrhagic fever with renal syndrome (HFRS) nationwide.Methods:HFRS monitoring data from 2004 to 2018 were collected from the National Public Health Science Data Center (https://www.phsciencedata.cn/). The trend of incidence rate of HFRS was analyzed by joinpoint regression, and the linear trend was estimated by annual percentage change (APC) and average annual percentage change (AAPC). Bayesian Age-Period-Cohort (BAPC) analysis of the effects of age, period, and birth cohort on HFRS cases was conducted, with age, period, and birth cohort used as reference for the 40 - 44 age group, 2011, and 1968, respectively, the RR and 95% CI were calculated. Results:From 2004 to 2018, a total of 190 197 HFRS cases were reported nationwide, with an average annual incidence rate of 0.95/100 000. Among them, the highest incidence rate of HFRS was 1.93/100 000 in 2004. Since 2007, it had continued to fluctuate below 1.00/100 000, ranging from 0.66/100 000 to 0.99/100 000. Joinpoint regression fitting results showed that the overall incidence of HFRS in China was declining (AAPC = - 7.33%, 95% CI: - 8.07% - - 6.58%, P < 0.001); the APCs from 2004 to 2007, 2007 to 2009, and 2012 to 2016 were - 32.00%, - 8.74%, and - 9.02%, respectively, all showed a downward trend( P < 0.05); the APCs from 2009 to 2012 and from 2016 to 2018 were 14.69% and 11.38%, respectively, both showed an upward trend ( P < 0.05). HFRS cases were reported in all age groups, and the reported incidence rate showed a unimodal distribution with age. Among them, the highest incidence rate was in the 50 - 54 age group (1.75/100 000), and the lowest incidence rate was in the 0 - 4 age group (0.03/100 000); the proportion of cases in the age group of 60 years and above increased from 9.75% in 2004 to 25.90% in 2018, showed an increasing trend year by year (χ 2trend = 9 210.90, P<0.001). The analysis results of the BAPC model showed that in the age effect analysis, compared with the reference age group, there was no significant difference in the incidence risk among the age groups of 15 - 79 years old ( P > 0.05), while the incidence risk was lower in the age groups of 14 years old and below, and 80 years old and above ( RR < 1, P < 0.05). In the analysis of period effects, compared with the reference year, the incidence risk was higher from 2004 to 2006 and from 2012 to 2014 ( RR > 1 , P < 0.05), and lower from 2008 to 2010 and from 2017 to 2018 ( RR < 1, P < 0.05); the overall trend was consistent with the descriptive analysis of onset period. In the analysis of birth cohort effect, compared with the reference cohort, the population born between 1920 - 1935 and 1970 - 2018 had lower incidence risk ( RR < 1, P < 0.05); but the risk of disease in the population born after 2003 showed an upward trend. Conclusions:The HFRS epidemic in China has decreased from 2004 to 2018, but the downward trend in recent years is not significant. The incidence risk has increased among people born after 2003. The population aged 60 and above is a key group for further controlling the HFRS epidemic in China.

Objective:To evaluate the safety and validity of perioperative antimicrobial prophylaxis with different administration period in patients undergoing transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH).Methods:This prospective randomized controlled clinical trial was conducted on patients who underwent TURP in the Second Affiliated Hospital of Anhui Medical University from July 2022 to December 2023. The patients were randomly assigned to the experimental group and the control group in a 1∶1 ratio using a randomized block design. Inclusion criteria: age 55-78 years old, the indication of benign prostatic hyperplasia surgery, preoperative urine routine examination showed no pyuria or bacteriuria, preoperative catheterization being not reserved, postoperative pathology confirmed BPH and informed consent obtained. Exclusion criteria: severe heart, lung, brain and other diseases which could not tolerate anesthesia and surgery, complicated with bladder stones or bladder tumors, diabetic patients with poor glycemic control, immunosuppressive agents being administered. Patients in the experimental group received a single dose of cephalosporins or fluoroquinolones 30 minutes or 2 hours before surgery, while patients in the control group received a second dose 12 hours or 24 hours after the first dose. The primary outcome was the incidence of urinary tract infectious presenting fever (body temperature ≥38.5℃) within 1 week after surgery, while the white blood cell count, C-reactive protein concentration, serum heparin-binding protein concentration, red and white blood cell count in urine, the incidence of bacteriuria, pulmonary infection, and postoperative hospital stay were defined as secondary outcomes. The safety index was the incidence of adverse reactions of antibiotics.Results:A total of 180 patients were enrolled in this study, including 90 cases in each experimental group or control group. Two groups of patients had no significant difference ( P>0.05) in age [(71.7±3.9) and (69.9±4.8) years], prostate volume [55.0 ml(39.5, 62.0) and 52.5(45.5, 68.5) ml], operation time [(58.8±17.0) min vs. (60.9±16.7) min], and postoperative indwelling catheter days [3.0(3, 4) d vs. 3.8(3, 4) d]. The incidence of fever within 1 week after surgery was 7.8%(7/90) in the experimental group and 5.6%(5/90) in the control group, respectively, and the difference was not statistically significant ( P=0.550). Our data demonstrated that the white blood cell count [(10.5±1.2)×10 9/L vs. (9.7±4.1)×10 9/L], C-reactive protein concentration [(43.0±27.9) mg/L vs. (53.1±29.9) mg/L] and heparin-binding protein concentration [(44.7±19.4) ng/ml vs. (37.8±23.5) ng/ml], urine red blood cell count [4 768.2(2 387.9, 10 496.5)/μl vs. 6 577.2(3 691.5, 7 636.8) /μl], urine white blood cell count [447.1(283.9, 637.0)/μl vs 242.8(109.7, 691.8)/μl] were mildly elevated in two groups without significant difference ( P>0.05). The incidence of postoperative pulmonary infection [3.3% (3/90)] vs. 2.2% (2/90)], bacteriuria [6.7% (6/90) vs. 8.9% (8/90)], postoperative hospital stay [4.5(4.0, 5.1) days vs. 4.5(4.0, 5.5) days] also showed no significant difference ( P>0.05). While the incidence of adverse reactions of antibiotics in the experimental group 3.3% (3/90) was significantly lower than that in the control group 11.1% (10/90) ( P=0.044). Conclusions:A single-dose antibiotic administration as a perioperative antimicrobial prophylaxis is safe and effective for patients undergoing TURP who do not have preoperative pyuria or indwelling catheter.

Objective:To evaluate the safety and validity of perioperative antimicrobial prophylaxis with different administration period in patients undergoing transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH).Methods:This prospective randomized controlled clinical trial was conducted on patients who underwent TURP in the Second Affiliated Hospital of Anhui Medical University from July 2022 to December 2023. The patients were randomly assigned to the experimental group and the control group in a 1∶1 ratio using a randomized block design. Inclusion criteria: age 55-78 years old, the indication of benign prostatic hyperplasia surgery, preoperative urine routine examination showed no pyuria or bacteriuria, preoperative catheterization being not reserved, postoperative pathology confirmed BPH and informed consent obtained. Exclusion criteria: severe heart, lung, brain and other diseases which could not tolerate anesthesia and surgery, complicated with bladder stones or bladder tumors, diabetic patients with poor glycemic control, immunosuppressive agents being administered. Patients in the experimental group received a single dose of cephalosporins or fluoroquinolones 30 minutes or 2 hours before surgery, while patients in the control group received a second dose 12 hours or 24 hours after the first dose. The primary outcome was the incidence of urinary tract infectious presenting fever (body temperature ≥38.5℃) within 1 week after surgery, while the white blood cell count, C-reactive protein concentration, serum heparin-binding protein concentration, red and white blood cell count in urine, the incidence of bacteriuria, pulmonary infection, and postoperative hospital stay were defined as secondary outcomes. The safety index was the incidence of adverse reactions of antibiotics.Results:A total of 180 patients were enrolled in this study, including 90 cases in each experimental group or control group. Two groups of patients had no significant difference ( P>0.05) in age [(71.7±3.9) and (69.9±4.8) years], prostate volume [55.0 ml(39.5, 62.0) and 52.5(45.5, 68.5) ml], operation time [(58.8±17.0) min vs. (60.9±16.7) min], and postoperative indwelling catheter days [3.0(3, 4) d vs. 3.8(3, 4) d]. The incidence of fever within 1 week after surgery was 7.8%(7/90) in the experimental group and 5.6%(5/90) in the control group, respectively, and the difference was not statistically significant ( P=0.550). Our data demonstrated that the white blood cell count [(10.5±1.2)×10 9/L vs. (9.7±4.1)×10 9/L], C-reactive protein concentration [(43.0±27.9) mg/L vs. (53.1±29.9) mg/L] and heparin-binding protein concentration [(44.7±19.4) ng/ml vs. (37.8±23.5) ng/ml], urine red blood cell count [4 768.2(2 387.9, 10 496.5)/μl vs. 6 577.2(3 691.5, 7 636.8) /μl], urine white blood cell count [447.1(283.9, 637.0)/μl vs 242.8(109.7, 691.8)/μl] were mildly elevated in two groups without significant difference ( P>0.05). The incidence of postoperative pulmonary infection [3.3% (3/90)] vs. 2.2% (2/90)], bacteriuria [6.7% (6/90) vs. 8.9% (8/90)], postoperative hospital stay [4.5(4.0, 5.1) days vs. 4.5(4.0, 5.5) days] also showed no significant difference ( P>0.05). While the incidence of adverse reactions of antibiotics in the experimental group 3.3% (3/90) was significantly lower than that in the control group 11.1% (10/90) ( P=0.044). Conclusions:A single-dose antibiotic administration as a perioperative antimicrobial prophylaxis is safe and effective for patients undergoing TURP who do not have preoperative pyuria or indwelling catheter.

Objective: To explore the social functioning characteristics of children with co ocurrence of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) for intervention reference. Methods: The Chinese Version of Swanson Nolan and Pelham, Version IV Scale-Parent Form(SNAP-IV), the Chinese Version of Weiss Functional Impairment Scale-Parent(WFIRS-P), and the Questionnaire-Children with Difficulties (QCD) were applied to 192 children with ADHD, 243 children with co occurrence of ADHD and ODD, who firstly visited the Department of Children Psychological Health of Zhuhai Maternal and Child Health Care Hospital, and 118 healthy control children from a school in Zhuhai. Results: The scores of attention deficit factor in SNAP-Ⅳ scale of children in three groups were[1.9(1.7, 2.1), 1.8(1.6, 1.9), 1.0(0.6, 1.2)], the scores of hyperactive impulsivity were[1.8(1.4, 2.1), 1.6(1.1, 1.8), 0.7(0.2, 1.0)] the scores of oppositional defiant were[1.6(1.5, 1.9), 1.0(0.8,1.1), 0.8(0.5, 1.0)], the differences were statistically significant( H=268.44, 237.97, 418.66, P <0.01). The dimensions and total scores of the three groups of children s WFIRS-P scale were family[0.8(0.6, 1.1), 0.6(0.3, 0.8), 0.3(0.1, 0.6)]; learning and school[0.8(0.5, 1.1), 0.8(0.5, 1.0), 0.3(0.1, 0.5)]; life skills[1.0(0.7, 1.2), 0.8(0.6, 1.0), 0.6(0.4, 0.8)]; self management [1.0(0.3, 1.0), 0.7(0.3, 1.0), 0.3(0.0, 0.7)]; social activities [0.7(0.4, 1.0), 0.6(0.3, 0.9), 0.3(0.0, 0.4 )]; adventure activities[0.3(0.2, 0.5), 0.2(0.1, 0.4), 0.1(0.0, 0.2)]; the total score[0.8(0.6, 1.0), 0.6(0.5, 0.8), 0.4( 0.2 , 0.6)], the difference between the groups was statistically significant( H=108.82, 122.45, 60.17, 40.58, 96.17, 76.57, 138.30, P <0.01). The difference between the QCD scale scores of children in the three groups was statistically significant[30.0( 24.0 , 37.0), 32.0(27.0, 40.0), 47.0(37.0, 52.3), H=124.65, P <0.01). Multiple regression analysis showed that attention deficit, and oppositional defiant symptoms were associated with both the total WFIRS-P score and the QCD score of children( R 2= 0.40 , 0.25, P <0.05). Conclusion Children with co occurrence of ADHD and ODD have more severe deficits in all dimensions of social functioning than children with ADHD, which might be associated with attention deficit and oppositional defiant symptoms.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRAS^G12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFR^L858R and EGFR^Δ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFR^T790M showed no difference compared to classical activating mutations without EGFR^T790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRAS^G12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFR^T790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Extracellular Matrix Proteins/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Treatment Outcome

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95％ confidence interval (CI), 1.01?1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95％ CI, 1.49?2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95％ CI, 0.48?1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95％ CI, 0.39?1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A (USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95％ CI, 0.32?0.82; P=0.0077), PFS (adjusted HR, 0.51; 95％ CI, 0.38?0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95％ CI, 2.75?8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95％ CI, 1.88?6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12C mutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.

Objective:To investigate the feasibility of combination of en-bloc resection of bladder tumor (ERBT) with the NBI(narrow band imaging) flexible cystoscopy, immunotherapy and chemotherapy in bladder-preserving treatments(called as TMT) for patients with stage T 2 bladder carcinoma. Methods:We retrospectively reviewed and analyzed a series of 16 patients with pT 2N 0M 0 pathologically confirmed. All patients are male with a median age of 63yr(56, 73yr). The American Association of Anesthesiologists scored ≤Ⅱ in 12 cases and Ⅲ in 4 cases. There were 9 cases with smoking history, 5 cases with hypertension, 3 cases with diabetes, and 2 cases with heart disease. The results of preoperative tissue biopsy were all urothelial carcinoma. All patients were taken lithotomy position and performed ERBT with NBI imaging technique and thulium-laser energy platform under general anesthesia. The tumor was brown and the surrounding normal mucosa was cyan in color. The procedure was ensured with a minimal tumor margin of 1cm and minimal rection depth to the deep musculi, and with the acquirement for the en-bloc specimen of which the basal site was marked afterwards, the patients all took a full length of chemoimmunotherapy (four cycles of Tislelizumab combined with Gemcitabine and cisplatin regimens) followed by a secondary ERBT. The perioperative data from sequential operations including complications were comprehensively analyzed for evaluating the therapeutic outcome and safety. All patients received a follow-up to detect efficacy and safety of the treatment with the primary end point of pCR, downgrading rate and objective response rate. Results:All operations were successfully completed. There was no obturator reflex, severe bleeding or grade Ⅱ bladder perforation, only 4 patients got a grade Ⅰ bladder perforation. The postoperative 30-day complication occured in 2 cases(1 pt with hematuresis, 1 pt with bladder irritation). The pathologic complete response rate and tumor downstaging rate were 100%. One patient recurred during a median follow-up of 13.0 months (6, 36 months).Conclusions:The En Bloc Resection of Bladder Tumor with the narrow band imaging (NBI) flexible cystoscopy has several remarkable advantages, including a better intra-operative visual, a lower complication rate and tumor residual. The combination of ERBT with immunotherapy and chemotherapy lead to affirmative curative effect and the feasibility for clinical application is relatively high.