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.

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.

OBJECTIVE To explore the protective mechanism of amifostine on acute radiation injury mice. METHODS Thirty C57BL/6J mice were randomly divided into normal control group， model group and amifostine group （150 mg/kg）， with 10 mice in each group. Thirty minutes before irradiation， the mice in the amifostine group were intraperitoneally injected with amifostine； normal control group and model group were given constant volume of normal saline intraperitoneally； then acute radiation injury was induced by 4 Gy X-ray radiation in both model group and amifostine group. The white blood cell count （WBC）， platelet count and red blood cell （RBC） count in mice were detected 2 hours before irradiation and on days 1， 4， 7， 10 and 14 after irradiation； the changes in the proportion of WBC （neutrophils， lymphocytes and monocytes） on the 7th day after irradiation were analyzed. The 16S rRNA high-throughput sequencing was used to analyze the structure of gut microbiota in mice feces on the 7th day after irradiation， then its correlation with WBC was analyzed. RESULTS The counts of WBC on the 1st， 4th， 7th and 10th day after irradiation， platelet count on the 10th day after irradiation and RBC count on the 1st day after irradiation in the amifostine group were significantly higher than those in model group （P＜0.05）. Compared with normal control group，β diversity of gut microbiome showed significant change， relative abundance of Firmicutes increased and that of Bacteroidetes decreased in model group. Amifostine could reverse the change in β diversity of gut microbiome， and the relative abundance of Bacteroidetes and Firmicutes. The model group consisted of four distinct species， namely Allobaculum， Erysipelotrichia， Erysipelotrichales and Erysipelotrichaceae， which were significantly negatively correlated with the proportion of peripheral blood lymphocytes （P＜0.01）； amifostine group consisted of two distinct species， namely Lactobacillus murinus and L. crispatus， which were significantly negatively correlated with the proportion of neutrophils （P＜0.05）. CONCLUSIONS Amifostine significantly improves irradiation-induced injury by regulating dysbiosis of LY201816） gut microbiota.

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 disclose phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B virus (Victoria) (BV) in the 2023-2024 influenza surveillance season in Beijing, and understand the matching with influenza vaccine component strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) in the 2023-2024 influenza surveillance season were collected from surveillance network labs in Beijing and BV strains were isolated through MDCK or chicken embryo culture. After extracting nucleic acid, HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity were conducted and the maximum likelihood method in Mega 5.0 software was used to construct the phylogenetic tree of HA gene. N-glycosylation sites of HA were performed online. Furthermore, three-dimensional structure of HA was available from SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) tests were performed to analyze antigenic characteristics of HA of BV strains.Results:Fifty-four BV strains were randomly selected to be analyzed further. Compared with the HA gene of this influenza season vaccine strain (B/Austria/1359417/2021), there are three amino acid mutations among all BV strains, two of which are located in two different antigenic determinants. Furthermore, the phylogenetic tree analysis revealed that only one subgroup of 1A.3a.2 was circulating simultaneously. All BV strains are located in Clade 1A.3a.2 subgroup, and in the same subgroup with that of the vaccine component BV strain in 2023-2024. All BV strains have the same glycosylation sites as that of the vaccine component BV strain in 2023-2024. Antigenic analysis showed that all BV strains were antigenically similar with its vaccine strain.Conclusions:In the 2023-2024 influenza surveillance season, the prevalent BV strains in the population in Beijing city are located in Clade 1A. 3a. 2 subgroup. The antigen matching between BV epidemic strains and vaccine BV components is relatively high during this surveillance season.

Objective To investigate the value of three-dimensional amide proton transfer(3D APT)imaging and multi-model diffusion weighted imaging(DWI)in evaluating the histological grade of cervical squamous cell carcinoma(CSCC).Methods A total of 54 patients with CSCC at different grades were prospectively included.All subjects underwent pelvic 3D APT and multi-b-value DWI sequences on a 3.0T MR scanner.Two radiologists blindly measured the amide proton transfer(APT)values of all continuous layers of the lesion,the apparent diffusion coefficient(ADC)of the mono-exponential-model of DWI,the ture-diffusion coefficient(D),pseudo-diffusion coefficient(D*),perfusion fraction(f)of intravoxel incoherent motion(IVIM)imaging,and the mean diffusivity(MD)and mean diffusion kurtosis(MK)values of diffusion kurtosis imaging(DKI).The receiver operating characteristic(ROC)curve was used to analyze the efficacy of each parameter in identifying different pathological grades of CSCC.Results The APT mean signal intensity(SImean),APT maximum signal intensity(SImax)and maximum mean diffusion kurtosis(MKmax)values of the high-grade group were statistically higher than those of the low-grade group,and the minimum apparent diffusion coefficient(ADCmin),minimum ture-diffusion coefficient(Dmin),and minimum mean diffusivity(MDmin)values were statistically lower than those of the low-grade group(P＜0.05).The area under the curve(AUC)increased after the combination of APT parameters and DWI parameters,which was obviously higher than that of a single parameter(P＜0.05).Conclusion Both APT and multi-model DWI are helpful to identify the degree of differentiation of CSCC,and the diagnostic value of combining the two is higher.

Objective:To analyze the clinical features and immunotherapy responsiveness of patients with myelin oligodendrocyte glycoprotein immunoglobulin G-antibody associated disease (MOGAD) with epilepsy, and display the risk factors of epilepsy in MOGAD.Methods:Eighty-nine patients with MOGAD diagnosed at the First Affiliated Hospital of Zhengzhou University between October 2019 and May 2023 were enrolled and classified into 2 groups upon MOGAD with ( n=29) or without epilepsy ( n=60). The Expanded Disability Status Scale (EDSS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used for evaluation of severity, and EDSS or CASE scores on the 30th day after first-line immunotherapy initiation lower than that on admission were defined as well treatment responsiveness. The differences of general data, clinical manifestations, cerebrospinal fluid (CSF) and peripheral blood biochemical examination results, and immunotherapy reactivity between the 2 groups were thoroughly explicated. In addition, the risk factors of epilepsy in MOGAD were analyzed by univariate and multivariate Logistic regression analysis. Results:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy were characterized by lower age of onset [24.5(10.3, 34.0) years vs 11.0(6.5, 20.0) years, Z=-2.348, P=0.019], higher percentage of male patients [43.3%(26/60) vs 75.9%(22/29), χ 2=8.326, P=0.004], higher virus infection rate [28.3%(17/60) vs 51.7%(15/29), χ 2=4.645, P=0.031], higher incidence of prodromal symptoms [11.7%(7/60) vs 34.5%(10/29), χ 2=6.586, P=0.010], higher blood-brain barrier breakdown rate [35.0%(21/60) vs 58.6%(17/29), χ 2=4.458, P=0.035], higher percentage of CSF albumin level>450 mg/L [48.3%(29/60) vs 75.9%(22/29), χ 2=6.056, P=0.014] and higher creatine kinase level [45.50(28.50, 69.75) U/L vs 57.50(41.75, 97.25) U/L, Z=-2.349, P=0.019]; more epilepsy [0(0) vs 29/29 (100.0%), χ 2=89.000, P<0.001] and disturbance of consciousness [0(0) vs 6/29(20.7%), χ 2=10.224, P=0.001] as clinical manifestations, and more cerebral cortex lesions [30/60(50.0%) vs 25/29(86.2%), χ 2=10.856, P=0.001] on magnetic resonance imaging. Nevertheless, the patients with MOGAD without epilepsy were featured with more visual impairment [23/60(38.3%) vs 3/29(10.3%), χ 2=7.406, P=0.007], limb weakness [18/60(30.0%) vs 1/29(3.4%), χ 2=8.209, P=0.004], sensory disturbance [15/60(25.0%) vs 0(0), Fisher exact probability test, P=0.002] and more cervical cord lesions [22/60(36.7%) vs 4/29(13.8%), χ 2=4.946, P=0.026] on magnetic resonance imaging. Immunotherapy responsiveness was relatively poor in the MOGAD with epilepsy group [EDSS score lower than that on admission: 15/29(51.7%) vs 46/60(76.7%), χ 2=5.641, P=0.018; CASE score lower than that on admission: 16/29(55.2%) vs 47/60(78.3%), χ 2=5.072, P=0.024] compared with the MOGAD without epilepsy group. Male was the independent risk factor of epilepsy in MOGAD ( OR=7.078, 95% CI 1.709-29.326, P=0.007). Conclusions:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy reported more male patients, lower age of onset and higher incidence of prodromal symptoms, blood-brain barrier dysfunction rate, virus infection rate, CSF albumin level and creatine kinase level; clinical phenotypes were mainly meningoencephalitis and more cerebral cortex lesions were shown on magnetic resonance imaging. MOGAD with epilepsy was closely related to poor immunotherapy responsiveness, and gender was found to be the independent risk factor for epilepsy in MOGAD.

Objective:To analyze the lympho-vascular space invasion (LVSI) in different molecular subtypes of the cancer genome atlas (TCGA) molecular subtypes of endometrial cancer (EC) and to evaluate the prognostic value of LVSI in EC patients with different molecular subtypes.Methods:A total of 258 patients diagnosed EC undergoing surgery in Peking University People′s Hospital from January 2016 to June 2022 were analyzed retrospectively. Among 258 patients, 14 cases were classified as POLE-ultramutated subtype, 43 as high-microsatellite instability (MSI-H) subtype, 155 as copy-number low (CNL) subtype, and 46 as copy-number high (CNH) subtype. Fifty-four patients were positive for LVSI, while 203 tested negative.Results:(1) The incidence of LVSI was found to be highest in the CNH subtype (32.6%,15/46), followed by the MSI-H subtype (27.9%, 12/43), the CNL subtype (16.9%, 26/154), and the POLE-ultramutated subtype (1/14), with statistically significant differences ( χ2=7.79, P=0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all P<0.05), except for the POLE-ultramutated subtype. The grade, lymph node metastasis, and the expression of nuclear antigen associated with cell proliferation (Ki-67) were significantly higher in LVSI positive patients than those in LVSI negative EC patients with both MSI-H and CNL subtypes (all P<0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all P<0.05). (3) Of the 257 EC patients, 25 cases recurred during the follow-up period, with a recurrence rate of 9.7% (25/257); among them, the recurrence rate of LVSI positive patients was 22.2% (12/54), which was significantly higher than those with LVSI negative (6.4%, 13/203; χ2=12.15, P<0.001). During the follow-up period, none of the 14 patients with POLE-ultramutated had recurrence; among CNL patients, the recurrence rate was 19.2% (5/26) in LVSI positive patients, which was significantly higher than that in LVSI negative ones (5.5%, 7/128; χ2=3.94, P=0.047); where as no difference were found in both MSI-H [recurrence rates in LVSI positive and negative patients were 2/12 and 9.7% (3/31), respectively] and CNH subtype [recurrence rates between LVSI positive and negative patients were 5/15 and 9.7% (3/31), respectively] EC patients (both P>0.05). After log-rank test, the 3-year recurrence free survival (RFS) rate were significantly lower in LVSI positive patients from CNL subtype and CNH subtype than those in LVSI negative patients (CNL: 80.8% vs 94.5%; CNH: 66.7% vs 90.3%; both P<0.05). (4) Lymph node metastasis ( HR=6.93, 95% CI: 1.15-41.65; P=0.034) had a significant effect on the 3-year RFS rate of EC patients with MSI-H subtype. Multivariate analysis revealed that PR expression ( HR=0.04, 95% CI: 0.01-0.14; P<0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. Conclusions:LVSI has the highest positivity rate in CNH subtype, followed by MSI-H subtype, CNL subtype, and the lowest positivity rate in POLE-ultramutated subtype. LVSI is significantly associated with poor prognosis in CNL subtype patients and may affect the prognosis of CNH subtype patients. However, LVSI is not an independent risk factor for recurrence across all four TCGA molecular subtypes.