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 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.

Objective:To evaluate the efficacy and safety of endoscopic biliary drainage for biliary fistula.Methods:Data of consecutive 409 biliary fistula patients who were treated and diagnosed at the First Medical Center of Chinese PLA General Hospital from November 2002 to November 2022 were reviewed, and 53 patients who received endoscopic retrograde cholangiopancreatography (ERCP) drainage were finally included. General information, procedural conditions, clinical outcomes and adverse events were analyzed. The patients were categorized into two groups: the endoscopic retrograde biliary drainage (ERBD) group ( n=46) and the endoscopic nasobiliary drainage (ENBD) group ( n=7). Procedural characteristics, operation outcomes, and operation time were compared between the two groups. Results:There were 36 males and 17 females, with the age of 52.2±12.7 years, among whom 58.5% (31/53) were secondary to cholecystectomy. Clinical success was achieved in 83.0% (44/53) patients, with the operation time of 27.0 (13.5, 33.5) minutes and the treatment session of 1 (1, 2). The time to resolution was 89 (47, 161) days. The success rate of ERCP for low-grade biliary fistula was higher compared with that of high-grade biliary fistula [96.4% (27/28) VS 68.0% (17/25), χ2=7.57, P=0.006]. Bridging drainage achieved higher success rate compared with that of non-bridging drainage [91.7% (33/36) VS 64.7% (11/17), χ2=5.95, P=0.015], while different diameters of stents (≥10 Fr VS <10 Fr) achieved similar success rate [81.8% (27/33) VS 84.6% (11/13), χ2=0.05, P=0.822]. Adverse events occurred in 10 patients (18.9%), including 6 pancreatitis, 2 bleeding, 1 cholangitis and 1 death. Except for 1 death, 9 other adverse events were mild and managed with conservative treatment without interventions. There was no significant difference in clinical success rate [6/7 VS 82.6% (38/46), χ2=0.04, P=0.838] or the median operation time [28.0 min VS 23.0 min, Z=0.38, P=0.774] between ENBD group and ERBD group. Conclusion:Endoscopic biliary drainage is safe and effective for biliary fistula. ENBD and ERBD have comparable clinical efficacy. ERCP for low-grade biliary fistula may achieve a higher success rate, and bridging drainage may facilitate fistula resolution.

Objective:To investigate the predictive value of F-2-fluoro-2-deoxy-D-glucose ( 18F-FDG) PET-CT metabolic parameters for the recurrence of type 1 autoimmune pancreatitis (AIP). Methods:Eighty-six patients with type 1 AIP who met the International Consensus Diagnostic Criteria (ICDC) and underwent 18F-FDG PET-CT before interventional treatment at the PLA General Hospital between May 2009 and June 2021 were included and divided into recurrence group ( n=43) and no-recurrence group ( n=43) according to whether they recurred after treatment. The standard uptake value (SUV)≥2.5 fixed threshold was used to outline the pancreatic lesion volume of interest (VOI) in three dimensions, and the three-dimensional diameter of the lesion, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), target-to-bench ratio (TBR) and standardized uptake value ratio (SUVR) were measured to compare the clinical characteristics, biochemical indices and treatment of the two groups; univariate and multifactorial regression analysis were used to examine 18F-FDG PET/CT visual indices of pancreatic lesions and extra-pancreatic involved organs as well as metabolic parameters in the two groups. A recurrence prediction model was constructed and its predictive efficacy was assessed. Results:The proportion of patients receiving glucocorticoid maintenance therapy was significantly higher in the no-recurrence group than in the recurrence group (58% vs 23.3%), and the serum IgG4 levels before treatment were significantly higher in the recurrence group [(15 309±11 724) mg/L vs (8 816±7 169) mg/L]. The results of univariate analysis showed that the proportion of extra-pancreatic salivary gland involvement and VOI, SUVmax, SUVpeak, SUVR, TBR, MTV, and TLG were significantly higher in the recurrence group than in the no-recurrence group, and the differences were statistically significant (all P values <0.05); the results of multivariate analysis showed that VOI ( OR=1.012, 95% CI 1.001-1.023 ), SUV max ( OR=1.398, 95% CI 1.029-1.899), SUV peak ( OR=1.408, 95% CI1.002-1.978), SUVR ( OR=1.977, 95% CI1.036-3.771) and MTV ( OR=1.012, 95% CI1.000- 1.022) in the recurrence group were significantly higher than those in the no-recurrence group, and all differences were statistically significant (all P values <0.05). The prediction model was constructed by multifactorial binary logistic regression analysis of SUVR>2, MTV>36 cm 3, and IgG4>11 400 mg/L, which had an AUC of 0.800 (95% CI 0.704-0.897), sensitivity of 81.4% (95% CI 0.661-0.911), specificity of 74.4% (95% CI 0.585-0.860), and prediction accuracy of 77.9%. Conclusions:18F-FDG PET/CT metabolic parameters can be used as predictors of type 1 AIP recurrence; a multiparameter model constructed based on metabolic parameters SUVR, MTV and IgG4 has a good predictive efficacy for predicting type 1 AIP recurrence.

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 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.

Objective:To establish a simple, rapid and low-cost 2019 novel coronavirus (2019-nCoV) neutralizing antibody detection method.Methods:The 2019-nCoV RBD specific immunoglobulin G (RBD-IgG) detection method was established based on the principle of quantum dot immunochromatography(QDs), and the detection was evaluated by using of sera from coronavirus disease 2019 (COVID-19) convalescent patients ( N = 97), vaccinated donors ( N = 82) and healthy donors ( N = 299). The suitability of fingertip blood was evaluated by matching blood samples with peripheral blood ( N=54). Results:The 2019-nCoV RBD-IgG detection method based on QDs was successfully established. The detection result of QDSs had strong correlation ( Spearman r > 0.73, P < 0.000 1) and good consistency ( Kappa=0.93, P < 0.01) with the result of micro-neutralization test(MNT). The sensitivity and specificity were 92% and 99%, respectively. There was high correlation ( Spearman r =0.932 6, P < 0.000 1) and no significant difference ( P=0.102 6) between result of fingertip blood and peripheral blood. Fingertip blood can be used as a surrogate sample for testing. Conclusions:The 2019-nCoV neutralizing antibody detection method established in this study can provide an immediate, efficient and low-cost method selection for the assessment of herd immunity status, and provide technical support for the herd immunity monitoring of 2019-nCoV vaccinated population and the prevention and control of the epidemic.