OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

Objective To validate the efficacy of the prediction model for difficulty of peroral endoscopic myotomy (POEM) through an independent cohort. Methods A total of 617 patients with achalasia who underwent POEM at the Endoscopy Center of Zhongshan Hospital, Fudan University from January 2021 to December 2023 were included. The general data of patients were collected, and the predictive value of the prediction model for POEM difficulty in the validation cohort was estimated. The stratified analysis was undergone according to the difficulty risk scores. Results In 617 consecutive patients, technical difficulty was observed in 90 cases (14.6%). The predictive model demonstrated moderate discriminatory capacity with an area under the receiver operating characteristic curve (AUC) of 0.711 (95%CI 0.643-0.780). Patients were stratified into three risk categories according to the difficulty risk scores: low-risk (＜0.1), medium-risk (0.1-0.25), and high-risk (≥0.25). The corresponding technical difficulty rates were 7.3%, 16.9%, and 51.6%, respectively. Conclusion The prediction model for POEM difficulty built by our center shows good stability and discrimination, and has good clinical application value.

AIM: To observe the clinical outcomes of Phorcides analytic engine-assisted topography-guided personalized laser assisted in situ keratomileusis(LASIK)for the treatment of myopia and astigmatism in virgin eyes with the refractive astigmatism significantly deviating from corneal topography.METHODS: Retrospective clinical study. A total of 32 cases(42 eyes)with myopia and astigmatism that received corneal topography-guided personalized LASIK in the Ophthalmology Refractive Surgery Center of the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to March 2021 were selected. The uncorrected distance visual acuity(UDVA), best corrected distance visual acuity(CDVA), refractive state and aberrations before and at 6 mo after surgery were recorded.RESULTS: There were 15 males and 17 females, with an age of 23.00(18.00, 29.25)years old; preoperative sphere was -5.75(-6.25, -4.00)D, and cylinder was -0.75(-1.38, -0.25)D. At 6 mo postoperatively, the UDVA exceeded the preoperative CDVA in 19 eyes(45%). The spherical equivalent(SEQ)of all eyes(100%)was -0.50 to +0.50 D at 6 mo postoperatively, and the postoperative SEQ of 23 eyes(55%)was -0.13 to +0.13 D. There were 33 eyes(79%)had a postoperative astigmatism ≤ 0.25 D, the target-induced astigmatism(TIA)was 0.94±0.96 D, and the surgically induced astigmatism(SIA)was 0.94±0.86 D, with no statistical significance between TIA and SIA(P>0.05). The astigmatism axial deviation ranged from -5° to +5° in 33 eyes(79%)at 6 mo postoperatively. Compared to pre-operation, the total higher-order aberrations and spherical aberrations within the central 6 mm diameter of the anterior corneal surface increased at 6 mo postoperatively(Z=-3.778, P<0.001; Z=-4.929, P<0.001); the postoperative coma aberrations had no change(Z=-1.763, P=0.078); the postoperative trefoil aberrations decreased(Z=-2.490, P=0.013). Compared to pre-operation, the Strehl ratio of the anterior corneal surface increased significantly at 6 mo after surgeries(t=-5.401, P=0.013).CONCLUSION: Using the Phorcides analytic engine to assist topography-guided personalized LASIK for the treatment of myopia and astigmatism in virgin eyes with the refractive astigmatism significantly deviating from topography-measured astigmatism can achieve good therapeutic effects. Postoperative UDVA exceeded preoperative CDVA in nearly half of the eyes, and the quality of postoperative corneal imaging was improved.

ObjectiveA qualitative analysis method was established for the composition of Astragali Radix（AR） before and after rice stir-frying. On the basis of systematic characterization of the chemical compositions in AR and stir-fried AR with rice（ARR）， the structures of their major compounds were deduced and identified， and the differential compositions between them were analyzed. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the samples of AR and ARR in positive and negative ion modes， respectively. The compounds were analyzed and identified through self-constructed databases， literature， and reference standards， etc. And the data were analyzed by chemometrics， in order to screen for the differential components between AR and ARR. ResultsA total of 123 compounds were identified in AR and ARR， including 41 flavonoids， 19 terpenoids， 26 organic acids， 8 amino acids， 5 nucleotides， 5 carbohydrates and 19 other compounds. Among them， there were 95 common components in both， 18 unique components in AR， and 10 unique components in ARR. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） results both showed that there were significant differences in the chemical constituents of AR before and after rice stir-frying， and a total of 26 constituents with differences in the content were screened out， including L-canavanine， L-pyroglutamic acid， L-phenylalanine， cis-caffeic acid， and malonylastragaloside Ⅰ. Among them， 19 constituents of ARR were down-regulated and 7 constituents were up-regulated by comparing with AR. ConclusionThis study clarifies that the chemical composition of AR and ARR is mainly composed of flavonoids， terpenoids， and organic acids， and analyzes the components with significant differences in content between the two in combination with chemometrics， and the differential components are dominated by amino acids， organic acids and terpenoids， which can provide reference for the subsequent quality control and material basis research.

Activity cliffs (ACs) are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target. ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures. Nonetheless, they also form a major source of prediction error in structure-activity relationship (SAR) models. To date, several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs. In this paper, we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet, tailored for ACs. Through extensive comparison with multiple baseline models on 30 benchmark datasets, the results showed that ACtriplet was significantly better than those deep learning (DL) models without pre-training. In addition, we explored the effect of pre-training on data representation. Finally, the case study demonstrated that our model's interpretability module could explain the prediction results reasonably. In the dilemma that the amount of data could not be increased rapidly, this innovative framework would better make use of the existing data, which would propel the potential of DL in the early stage of drug discovery and optimization.

Objective To investigate the correlation between the inflammatory burden index(IBI)and major adverse cardiovascular events(MACEs)in patients with ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI),and to assess the efficacy of IBI in predicting in-hospital and long-term MACEs.Methods This retrospective study included 465 STEMI patients who received PCI treatment in No.904 Hospital of Joint Logistics Support Force of PLA from Dec.2017 to Dec.2021.The IBI was calculated for each patient.The predictive value for in-hospital and long-term MACEs was evaluated using receiver operating characteristic(ROC)curves,and the area under curve(AUC)was calculated.The population was grouped based on the optimal IBI cut-off value for clinical characteristic analysis.Multivariate logistic regression and Cox regression analyses were used to identify factors independently associated with MACEs.The Kaplan-Meier estimator and log-rank test were used to assess the MACE risk of different IBI groups.Results The AUC value for predicting MACEs during hospitalization in STEMI patients using IBI was 0.687,and the AUC value for predicting long-term MACEs was 0.634.Multivariate logistic regression analysis revealed that a high IBI 102.33 mg/L)independently increased the risk of MACEs during hospitalization in STEMI patients(odds ratio=10.900,95％confidence interval[95％CI]4.273-29.180,P＜0.001).Multivariate Cox regression analysis further indicated that during long-term follow-up of STEMI patients,a high IBI(≥55.88 mg/L)independently predicted MACEs(hazard ratio=1.989,95％CI 1.128-3.506,P=0.018).Conclusion IBI is a valuable predictor for the occurrence of MACEs during hospitalization and long-term follow-up after PCI in STEMI patients.

Objective To explore the mechanism of Lkb1 regulated epithelial regeneration in asthma by airway organoid culture.Methods Lkb1f/f(the control group,n=10)and Scgb1a1CreER;Lkb1f/fmice(the Lkb1 knockout group,n=9)were taken to establish allergic asthma models by aerosol inhalation of ovalbumin(OVA).Bronchial lavage fluid(BALF)and lung tissue were collected.The number of inflammatory cells in BALF were counted.The amount of CLCA3 positive cells was compared by immunofluorescence staining of lung tissue sections.Club cells were selected by flow cytometry for organoid culture.The average diameter of organoids and organoid formation rate were calculated.Expression levels of goblet cell marker CLCA3,cilia cell markers FOXJ1 and AMPK in Club cells were detected by RT-PCR.Results There were no significant differences in the number of macrophages,eosinophils,neutrophils and lymphocytes in BALF between the control group and the Lkb1 knockout group.The number of CLCA3 positive cells were decreased after Lkb1 knockout.Results of organoid culture showed that the average diameter of organoids derived from Club cells and organoid formation rate were decreased after the absence of Lkb1.The expression of FOXJ1 was reduced.After Lkb1 deletion,the expression of AMPKα in Club cells were decreased and the proliferation of Club cells was inhibited.Activation of AMPK,the downstream signaling pathway of Lkb1,could attenuate the effect of Lkb1 deficiency on the regeneration of Club cells.Conclusion Lkb1 promotes the proliferation of airway progenitor cells by AMPK pathway.

Objective:To analyze clinical and histopathological diagnoses of patients with solid tumors localized on the perianal and external genitalia regions, aiming to help clinicians correctly identify benign and malignant tumors.Methods:A retrospective analysis was conducted on clinical, histopathological, and dermoscopic features, diagnosis and treatment of 389 patients diagnosed with solid tumors localized in the perianal and external genitalia regions in the Department of Dermatology, Peking University Third Hospital from January 2016 to May 2023.Results:Among the 389 patients with solid tumors in perianal and external genitalia regions, 123 were males and 266 were females, with the age being 8 - 89 (41.86 ± 16.62) years. Based on the histological classification of skin tumors, melanocytic tumors were the most common type (33.16% [129/389]), followed by other tumors (21.59%, 84/389), keratinocytic tumors (21.08%, 82/389), soft tissue and neural tumors (13.62%, 53/389), and appendageal tumors (10.54%, 41/389). There were 83.03% (323/389) of benign tumors and 16.97% (66/389) of malignant tumors. Melanocytic nevus was the most common benign tumor, mostly involving the labia majora of females and mons pubis of males. Among the malignant tumors, squamous cell carcinoma was relatively common in females (40%, 10/25), while extramammary Paget′s disease was relatively common in males (39.02%, 16/41). The initial misdiagnosis rate of Bowenoid papulosis was the highest (11/11), followed by squamous cell carcinoma (78.26%, 18/23) and basal cell carcinoma (40%, 4/10) ; there was no significant difference in the initial misdiagnosis rate between different gender groups or different age groups (both P>0.5). A total of 367 patients underwent surgical excision under local anesthesia and all showed a good prognosis; the remaining 22 with malignant tumors were treated with photodynamic therapy, extended resection, free flap transfer, etc., and experienced no recurrence during the follow-up of 3 months to more than 3 years. Conclusions:Solid tumors in the perianal and external genitalia regions were polymorphous, melanocytic tumors, keratinocytic tumors and other tumors accounted for a large proportion, while malignant tumors were relatively rare, and some were easily misdiagnosed. Most of the tumors in the regions had a good prognosis, without recurrence after the surgical resection.

Objective:To evaluate the efficacy and safety of chidamide combined with curcumin in the treatment of cutaneous T-cell lymphoma (CTCL) .Methods:Human CTCL cell lines HH and HuT-78 were cultured in vitro and treated with gradient concentrations of chidamide (0.4, 0.8, 1.6, 3.2, and 6.4 μmol/L) and curcumin (1.25, 2.5, 5, 10, and 20 μmol/L) alone or in combination, and the combination index (CI) of chidamide and curcumin for HH and HuT-78 cells was evaluated. Cultured HH/HuT-78 cells were divided into chidamide group (treated with 0.4 μmol/L chidamide), curcumin group (treated with 10 μmol/L curcumin), combination group (treated with 0.4 μmol/L chidamide + 10 μmol/L curcumin), and solvent control group (treated with dimethyl sulfoxide) ; after 48-hour treatment, the MTS assay was performed to evaluate the cell viability, flow cytometry to detect cell apoptosis and analyze cell cycle, and real-time quantitative PCR (RT-PCR) and Western blot analysis were conducted to determine the mRNA and protein expression of apoptosis-related genes nuclear factor (NF) -κB p65, B-cell lymphoma 2 (Bcl-2), and caspase-3, respectively. A tumor-bearing mouse model was established with HH cells in immunodeficient mice. These tumor-bearing mice were randomly divided into 4 groups: chidamide group (gavaged with 10 mg/kg chidamide), curcumin group (gavaged with 100 mg/kg curcumin), combination group, and solvent control group. The treatment was administered daily for 12 days, and body weight and tumor size were measured. On day 13, these mice were sacrificed, and tumor tissues were collected. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect apoptosis of tumor cells, and RT-PCR and Western blot analysis were conducted to determine the expression of apoptosis-related genes and proteins. Differences among multiple groups were analyzed using one-way analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:The CI values of chidamide (0.4 - 6.4 μmol/L) combined with curcumin (1.25 - 20 μmol/L) were all < 1, indicating a synergistic effect. After 48-hour treatment, the proliferation rates of HH and HuT-78 cells were significantly lower in the combination groups than in the chidamide groups and curcumin groups (all P < 0.05) ; HH and HuT-78 cells both showed significantly increased apoptosis rates in the combination groups compared with the chidamide groups, curcumin groups and control groups (HH cells: 70.47% ± 7.87% vs. 31.95% ± 9.43%, 37.23% ± 10.74%, 11.76% ± 5.65%, all P < 0.001; HuT-78 cells: 28.31% ± 1.70% vs. 21.29% ± 3.61%, 18.74% ± 1.82%, 3.18% ± 1.00%, all P < 0.001) ; in both HH and HuT-78 cells, the combination groups exhibited significantly increased caspase-3 mRNA expression and cleaved protein levels (all P < 0.05), but significantly decreased mRNA and protein expression of NF-κB p65 and Bcl-2 compared with the control groups, chidamide groups, and curcumin groups (all P < 0.05). On day 13 in the in vivo experiment, the tumor volume was significantly lower in the combination group (107.00 ± 43.10 mm 3) than in the control group (1 833.00 ± 281.20 mm 3), chidamide group (453.30 ± 91.71 mm 3), and curcumin group (548.50 ± 90.72 mm 3, all P < 0.05) ; the apoptosis level of tumor cells detected by TUNEL staining was significantly higher in the combination group than in the chidamide group, curcumin group, and control group (all P < 0.05) ; compared with the chidamide group, curcumin group, and control group, the combination group showed significantly increased expression of caspase-3 mRNA and cleaved caspase-3 protein (all P < 0.05), but significantly decreased mRNA and protein expression of NF-κB p65 and Bcl-2 (all P < 0.05). During the treatment period, there was no significant difference in the body weight of mice among the 4 groups ( P < 0.05) ; after sacrifice of the mice, no abnormalities were found in histopathological manifestations of their resected visceral tissues, blood routine test results, or liver and kidney function indicators. Conclusion:The combination of chidamide and curcumin had a synergistic antitumor effect on CTCL, which may be related to the inhibition of cell proliferation and induction of tumor cell apoptosis.