Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Outcome Assessment, Health Care ; Reference Standards ; Reproducibility of Results ; Research Design ; Clinical Trials as Topic

Objective:To investigate the long-term efficacy and complications of augmentation uretero-enterocystoplasty (AUEC).Methods:The clinical data of 262 patients with lower urinary tract dysfunction who underwent AUEC at our center from January 2003 to June 2022 were analyzed retrospectively. There were 193 males and 69 females, the median age was 24 (4, 67) years, the median disease duration was 12.0 (0.2, 56.0) years and the preoperative creatinine was 91.5 (68.1, 140.0) μmol/L. 320 ureters had high-grade UUTD, 216 ureters had VUR, 14 of which had low-pressure reflux.The number of low-grade VUR ureter was 22 (10.2%) and the number of high-grade VUR ureter was 194 (89.8%). Video-urodynamics showed that the maximum bladder capacity was 102 (47, 209) ml, the maximum detrusor pressure was 33.0 (15.5, 50.5) cmH 2O, and the bladder compliance was 6.4 (3.0, 12.3) ml/cmH 2O. All patients underwent AUEC. The surgical method is to cut a segment of sigmoid colon, open the sigmoid colon along the mesenteric margin, fold and suture it into " U" or " S" shaped intestinal mesh according to the principle of " detubulization" . At the same time, perform ureteroplasty and replanting, and then anastomosis the intestinal mesh with the opened bladder flap to form an expanded new bladder. Follow-up was performed via outpatient clinic or telephone. The creatinine, maximum bladder capacity, maximum detrusor pressure, bladder compliance, ureteral reflux and upper urinary tract dilatation were compared preoperatively and postoperatively. The postoperative complications were also evaluated. Results:The median follow-up time was 57.4 (4, 151) months after surgery. At 1-3 months after surgery, the maximum bladder capacity and bladder compliance increased to 303.9% and 189.9% of the preoperative level, and the maximum detrusor pressure decreased to 63.6% of the preoperative level. At 6-10 years after surgery, the maximum bladder capacity and bladder compliance increased to 490.2% and 627.9% and the maximum detrusor pressure decreased to 25.8% of the preoperative level. The UUTD of the patients was significantly reduced after surgery. The number of the high grade UUTD decreased to 116 (116/398, 29.2%) at 1-3 months and 51 (51/274, 18.6%) at 4-6 months. At 6-10 years, the number of the high-grade UUTD decreased to 4 (4/76, 5.3%) ( P<0.001), which was significantly lower than that before operation. The VUR was significantly relieved after operation, and 393 ureters had no VUR at 1-3 months, accounting for 97.8% (393/402) of the total ureters. Sustained remission of VUR was observed during follow-up. 73 ureters had no VUR at 6-10 years, accounting for 96.1% (73/76) of total ureters ( P<0.001). Patients' creatinine decreased to 79.0 (65.0-128.2) μmol/L at 1-3 months postoperatively, with a downward trend but no statistical difference, and creatinine levels were not significantly elevated at any postoperative time point compared with preoperative levels ( P>0.05). Postoperative complications included metabolic acidosis in 26 cases (9.9%), vesicoureteral anastomosis stenosis in 15 cases (5.7%), recurrent urinary tract infection in 16 cases (6.1%), and urinary calculi in 20 cases (7.6%), and intestinal obstruction requiring laparotomy in 8 cases (3.1%), all of them could be improved after treatments. Conclusions:AUEC is a safe and effective method for treating high-grade VUR or VUR with impaired anti-reflux mechanism, high-grade UUTD or UUTD with ureteral or vesicoureteral junction obstruction, and all of the complications can be improved after treatment. This technique can increase the bladder capacity and compliance, reconstruct the anti-reflux mechanism, and release upper urinary tract obstruction. It may play an important role in stabilizing and protecting the residual renal function from further deterioration.

Objective:To investigate the long term outcome of artificial urinary sphincter implantation for patients with stress urinary incontinence.Methods:The data of 46 patients who underwent artificial urethral sphincter implantation in China Rehabilitation Research Center from April 2002 to April 2022 were retrospectively analyzed.The patients’ age ranged from 19-80 years old (median 45.6 years). There were 45 males and 1 female. The history of illness was 8 months to 33 years. The patients category were urethral injuries associated urinary incontinence ( n=24), neurogenic urinary incontinence ( n=9) and post-prostatectomy incontinence ( n=13). Preoperative daily pad usage was 3.5±1.0. The impact of incontinence on the quality of life (QOL)measured by the visual analogue scale (VAS)was 7.1±1.2. All 46 patients underwent artificial urethral sphincter implantation, of which 20 patients were treated with anticholinergic drugs (5 cases) or urinary tract related surgery (urethral stenosis incision in 2 cases, sphincterectomy in 3 cases, urethral dilation in 5 cases, urethral calculus lithotripsy in 1 case, and augmentation cystoplasty in 4 cases) before artificial urethral sphincter implantation. Of the 45 male patients, 25 patients had the transperineal approach and 20 had the trans-scrotal approach. The female case had a trans-retropubic approach. Different cuffs size was used based on individual circumference of bulbar urethra (45 male cases: 4.5cm in 16 cases, 4.0cm in 29 cases; one female case: 8.0cm). Long-term surgical efficacy was evaluated. Assessments included postoperative urinary continence (socially continent: one pad per day or less; complete dry: wearing no pads), artificial urinary sphincter status and complications. The influences of patients of different etiologies, surgical approaches and cuff size on surgical results were compared. Results:The mean follow-up time was 7.1 years ranged from 6 months to 19 years. At the latest visit, 32 patients (69.6%) maintained the primary functional artificial urinary sphincter. Three patients (6.5%) had artificial urinary sphincter revisions and maintained continence with the new device. 11 patients (23.9%) removed the artificial urinary sphincter because of post-complications. Thirty-five patients were socially continent, of which 16 patients were totally dry, leading to the overall social continent rate as 76.1%(35/46). There was a significant reduction in pad usage to 1.2±0.6 diapers per day ( P<0.001). The impact of incontinence on the QOL measured by the VAS dropped to 2.6±1.9 ( P<0.001). The complication rate was 32.6%(15/46), including infections ( n=4), erosions ( n=5), mechanical failure ( n=3), dysurie ( n=2) and urethral atrophy ( n=1). There were no significant differences in social continent rate between patients with different etiologies[75.0%(18/24)vs. 66.7%(6/9) vs. 84.6%(11/13)], perioperative complications [37.5%(9/24)vs. 33.3%(3/9) vs. 23.1%(3/13)] and device re-intervention rate[37.5%(9/24) vs. 33.3%(3/9)vs. 15.4%(2/13)]. There were no statistically significant differences in postoperative complete dry rate [32%(8/25)vs. 40%(8/20), P=0.76] and postoperative device failure free rate [60%(15/25)vs. 80%(16/20), P=0.20] between trans-perineal group and trans-scrotal group. There was no statistically significant difference in postoperative social continent rate between 4.5cm cuff and 4.0 cuff[75%(12/16) vs. 65.5%(19/29), P=0.74]. Conclusions:Artificial urethral sphincter implantation is an effective treatment for stress urinary incontinence due to intrinsic sphincter deficiency. There was no difference in the continent rate and complication rate between patients of different etiologies, different surgical approaches and cuff size selection.

Objective To investigate the dynamic expression of transforming growth factor-β1 (TGF-β1) and heat shock protein 47 (HSP47) and explore their roles in the progression of hepatic fibrosis induced by Schistosoma japonicum infection. Methods Fifty female mice of the ICR strain were randomly divided into the infection group and the normal control group, of 25 mice in each group. Each mouse in the infection group was infected with 20 ± 1 cercariae of S. japonicum via the abdominal skin, while uninfected animals served as normal control. Five mice were sacrificed 4, 6, 8, 10 and 12 weeks post-infection and liver tissues were sampled. Serum HSP47 and TGF-β1 was determined using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of liver specimens were observed with hematoxylin & eosin (HE) staining. In addition, the synthesis of alpha 1 chain of type I collagen (COL1A1) was measured using Masson staining, and the mRNA expression of TGF-β1, HSP47 and COL1A1 was determined using real-time fluorescent quantitative PCR (qPCR) assay. Results During the period of S. japonicum-induced hepatic fibrosis, the serum HSP47 and TGF-β1 levels and the mRNA expression of TGF - β1, HSP47 and COL1A1 gradually increased with the progression of hepatic fibrosis. The serum levels of HSP47 and TGF-β1 were (179.26 ± 29.87) pg/mL and (22.37 ± 5.21) ng/mL 6 weeks post-infection, respectively, which were significantly greater than those [(150.29 ± 34.91) pg/mL and (18.54 ± 7.78) ng/mL, respectively] in the normal control group (both P values < 0.05). In addition, the mRNA expression of HSP47, COL1A1 and TGF-β1 was (0.86 ± 0.04), (1.17 ± 0.06) and (0.64 ± 0.13) in mouse liver specimens, which was significantly higher than that (0.23 ± 0.03, 0.20 ± 0.02 and 0.38 ± 0.02) in the normal control group (all P values < 0.01). Conclusions The expression of TGF-β1 and HSP47 during the period of S. japonicum-induced hepatic fibrosis is consistent with the progression of the hepatic fibrosis, and exhibits the same tendency with type I collagen expression. HSP47 is a novel promising diagnosis marker and therapeutic target for S. japonicum-induced hepatic fibrosis.

To evaluate the efficiency and safety between Wenxin Granule and antiarrhythmic drugs in the treatment of atrial fibrillation(AF). A total of 8 major electronic databases(CNKI, WanFang, VIP, CBM, Cochrane Library, Web of Science, PubMed, EMbase) were retrieved since the establishment of the database to January 10, 2019. Two reviewers extracted data, and assessed the methodological quality of the included studies. The Meta-analysis was made by RevMan 5.3 software. Finally, 42 studies involving 4 657 patients were included. The results of Meta-analysis showed that compared with antiarrhythmic drug, the combined administration with Wenxin Granule and antiarrhythmic drug had a better clinical efficiency(OR=3.37, 95%CI[2.69,4.22],I~2=0%,P<0.000 01)and efficacy on cardioversion(OR=2.32,95%CI[1.67,3.22],I~2=0%,P<0.000 01), with reduction in P_d(MD=-5.48,95%CI [-7.32,-3.64],I~2=0%,P<0.000 01)and P_(max)(MD=-9.91,95%CI[-12.86,-6.95],I~2=0%,P<0.000 01). The comparison between the combined application with Wenxin Granule and the single application of amiodarone showed a clinical efficiency(OR=2.89,95%CI[1.96,4.26],I~2=44%,P<0.000 01),and efficacy on sinus rhythm maintenance(OR=2.58,95%CI[1.82,3.66],I~2=3%,P<0.000 01). The comparison between the combined application with Wenxin Granule and the single application of amiodarone showed a clinical efficiency(OR=0.88,95%CI[0.53,1.46],I~2=0%,P=0.63). The combined treatment with Wenxin Granule has a better clinical efficiency in AF better than amiodarone, with no evidence for more benefits from the single administration with Wenxin Granules.
Anti-Arrhythmia Agents ; pharmacology ; Atrial Fibrillation ; drug therapy ; Combined Modality Therapy ; Drugs, Chinese Herbal ; pharmacology ; Electric Countershock ; Humans

OBJECTIVE: Mental disorders of the elderly population in China deserve attention. Social health is significantly associated with depression. This study aimed to evaluate the rate of depressive symptoms and to test the relationships between social health and depressive symptoms among a large sample of community-dwelling elderly adults. METHODS: We conducted a cross-sectional study among community-dwelling adults aged 60 years or above in Zhejiang Province, China. Face-to-face interviews were used to complete a structured questionnaire for all participants. We used the Social Health Scale for the Elderly (SHSE) to evaluate social health status and used the short form of the Geriatric Depression Scale to evaluate depressive symptoms. Multivariate logistic regression was used to evaluate the association between social health status and depressive symptoms. RESULTS: Of the total of 3757 participants included, 1887 (50.23%) were female, and the mean±standard deviation (SD) age was (70.0±8.3) years. The rate of depressive symptoms was 25.92%. The social health score was higher in non-depressed participants than in depressed participants (raw score 50.7 vs. 48.3, P<0.001). Participants with "moderate" or "good" social health had a significantly lower risk of depressive symptoms than those with "poor" social health (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.46-0.66 for moderate social health; OR=0.45, 95% CI: 0.35-0.60 for good social health). The association between social health and depressive symptoms was consistent across several subgroups. CONCLUSIONS Social health is significantly inversely associated with depressive symptoms. The SHSE may serve as an efficient screener to identify those elderly adults with social health deficits, but systematic assessment to guide intervention merits further investigation.
Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Depression/epidemiology* ; Female ; Health Status ; Humans ; Independent Living ; Logistic Models ; Male ; Middle Aged

OBJECTIVETo evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA).

METHODSThe clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed.

RESULTSThe 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×10/L, CD3T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions.

CONCLUSIONSThe children with SAA/VSAA who have an increased CD3T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.

Adolescent ; Anemia, Aplastic ; drug therapy ; genetics ; immunology ; mortality ; Child ; Child, Preschool ; Chromosome Aberrations ; Clonal Evolution ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Proportional Hazards Models ; Retrospective Studies

Objective To study the toxicokinetics of Cymermethrin and its metabolites in dog bile and provide evidence for forensic cases of identification of Cymermethrin poisoning. Methods 1/4LD50 doses of Cymermethrin were given to 6 male dogs by oral perfusion after the gallbladder fistula surgery on them,and their bile were collected at different time, in which Cymermethrin and its metabolites were extracted by Liquid-liquid extraction with dichloromethane and detected by HPLC-MS-MS. The qualitative analysis was based on retention time and MRM ions. The quantitative analysis was based on an internal standard method and calibration curve. Toxicokinetics equations of Cymermethrin and its metabolites in the bile were established from the c-t curves which were fitted by the WinNonlin toxicokinetics software meanwhie toxicokinetics parameters were obtained. Results The toxicokinetics of Cymermethrin met first-order dynamic equation. The Tmax of Cymermethrin(CYM), 3-phenoxybenzoic acid (3-PBA), 3-(2,2-Dichloroethenyl)-2,2-dimethyl-cyclopropanecarboxylate (DCVA) respectively were 1.52±0.30,1.29±0.04,0.93±0.41 h ; The Cmax of CYM, 3-PBA, DCVA respectively were 0.38±0.03,7.9±1.32,30.9±16.24 μg/mL ; The T1/2 of CYM, 3-PBA, DCVA respectively were3.93±0.71,1.36±0.11,4.49±2.81 h; Conclusion The toxicokinetics of Cymermethrin in dog bile met first-order dynamic equation ; The toxicokinetics model and parameters of Cymermethrin can provide evidence for forensic identification of Cymermethrin poisoning cases.