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.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Objective To explore the characteristics of the inhibitory effect of Evodiamine on the proliferation of activated T cells. Methods Mononuclear cells from peripheral blood (PBMCs) were obtained from healthy donors through density gradient centrifugation, and T cells were subsequently purified by using immunomagnetic bead separation. T cell activation was induced by employing anti-human CD3 and anti-human CD28 antibodies. T cells were treated with different concentrations of EVO (0.37, 1.11, 3.33, and 10)μmol/L. Flow cytometry was applied to evaluate the proliferation index, apoptosis rate, viability, CD25 expression levels, and cell cycle distribution of T cells. The expression levels of cytokines IL-2, IL-17A, IL-4, and IL-10 were quantified by using ELISA. Results 1.11, 3.33 and 10 μmol/L EVO effectively inhibited the proliferation of activated T cells, with an IC₅₀ of (1.5±0.3)μmol/L. EVO did not induce apoptosis in activated T cells and affect the survival rate of resting T cells. EVO did not affect the expression of CD25 and the secretion of IL-2 in activated T cells. EVO arrested the T cell cycle at the G2/M phase, resulting in an increase in G2/M phase cells, and exhibited a concentration-dependent effect. EVO did not affect the secretion of IL-4, IL-10 by activated T cells, but significantly inhibited the secretion of IL-17A. Conclusion EVO did not significantly affect the activation process of T cells but inhibited T cell proliferation by arresting the cell cycle at the G2/M phase and significantly suppressed the secretion of the pro-inflammatory cytokine IL-17A, which suggests that EVO has the potential to serve as a lead compound for the development of low-toxicity and high-efficiency immunosuppressants and elucidates the mechanisms underlying the anti-inflammatory and immunomodulatory effects of the traditional Chinese medicine Evodia rutaecarpa.
Humans ; Cell Proliferation/drug effects* ; Quinazolines/pharmacology* ; T-Lymphocytes/metabolism* ; Lymphocyte Activation/drug effects* ; Apoptosis/drug effects* ; Interleukin-4/metabolism* ; Interleukin-10/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-17/metabolism* ; Interleukin-2/metabolism* ; Cell Cycle/drug effects* ; Cells, Cultured

Porcine reproductive and respiratory syndrome (PRRS), caused by the porcine reproductive and respiratory syndrome virus (PRRSV), is one of the major diseases threatening the swine industry. This study aims to rationally design and optimize natural antimicrobial peptides to identify antiviral candidates with potent inhibitory activity against PRRSV, thereby establishing a foundation for the development of novel preventive and therapeutic agents targeting PRRS. In this study, with cecropin D (CD) as the parent peptide, three derivatives (CD-2, CD-3, and CD-4) were designed through amino acid substitutions. CD and derived peptides were obtained by solid-phase peptide synthesis. MS and reversed-phase (RP)-HPLC were employed for sequence identification, purification, and purity analysis. The secondary structures of the peptides were investigated by circular dichroism spectroscopy. CellTiter 96^® AQueous one solution cell proliferation assay was used to evaluate the cytotoxicity of the peptides. The inhibitory activities and mechanisms of the peptides against PRRSV were studied by Western blotting, RT-qPCR, and indirect immunofluorescence assay. The MS and RP-HPLC results showed that CD and derived peptides were successfully synthesized, with the purity reaching up to 95%. Circular dichroism analysis revealed that the CD derivatives exhibited more stable and abundant α-helices in a cell membrane-mimicking environment. The MTS assay indicated that all tested peptides at 100 μg/mL had negligible cytotoxicity. The experimental results of the action phase of the peptide against PRRSV demonstrated that the derived peptides significantly enhanced antiviral activities at the viral entry stage compared with the parent peptide. This enhancement was attributed to the introduction of lysine, tryptophan, and phenylalanine, which increased the hydrophobicity and positive charge of the peptides. These findings provide a theoretical basis for the application and structural optimization of antiviral peptides and may offer a new strategy for preventing and controlling PRRSV.
Porcine respiratory and reproductive syndrome virus/physiology* ; Animals ; Swine ; Antiviral Agents/chemistry* ; Porcine Reproductive and Respiratory Syndrome/virology* ; Virus Internalization/drug effects* ; Antimicrobial Peptides/chemistry*

Objective To investigate the effect of respiratory training based on core stability training on feedforward control in pa-tients with chronic nonspecific low back pain(CNLBP). Methods A total of 60 patients with CNLBP in Jiaxing Second Hospital from January,2022 to March,2023 were ran-domly divided into control group(n=30)and experimental group(n=30).Both groups received health educa-tion,physical factor therapy and core stability training,while the experimental group received respiratory training in addition,for four weeks.Visual Analogue Scale(VAS)score,Japanese Orthopaedic Association low back pain(JOA)score and Oswestry Dysfunction Index(ODI)were compared between two groups before and after treat-ment,while surface electromyography was used to detect the root mean square(RMS)and integrated electromy-ography(iEMG)of transversus abdominis,multifidus and triceps(movement muscles),and the activation se-quence and relative activation time of transversus abdominis,multifidus and triceps were calculated. Results After treatment,the scores of VAS,JOA and ODI improved significantly in both groups(|t|>8.515,P<0.001),and the scores were better in the experimental group than in the control group(|t|>2.089,P<0.05).RMS and iEMG of transversus abdominis and multifidus improved significantly after treatment in both groups(|t|>18.831,P<0.001),and were significantly better in the experimental group(|t|>3.481,P<0.05).The transversus abdominis and multifidus in both groups were activated before the movement muscles,and the relative activation time of transversus abdominis and multifidus increased in negative(|t|>48.115,P<0.001),the experimental group being better(|t|>3.229,P<0.05). Conclusion Combination of core stability training and respiratory training is beneficial in reducing the pain of patients with CNLBP,reducing the lumbar dysfunction,improving the order of muscle activation,and strengthening feed-forward control.

Objective:To understand and compare the clinical characteristics of children and adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.5 and BA.2 subtypes in Shanghai City.Methods:The clinical data of 524 children hospitalized with coronavirus disease 2019(COVID-19) at the Children′s Hospital of Fudan University during the period of BA.5 predominance from December 1, 2022 to January 20, 2023 were collected, which included age, gender, clinical symptoms and laboratory examination results. And the clinical data of household close contacts were also collected. The clinical data of children and their household contacts infected with Omicron BA.2 subtypes during the period of BA.2 predominance from April 4 to April 30, 2022 were collected and compared.The clinical characteristic of critical and non-critical cases, child and adult cases during the period of BA.5 predominance were compared.Statistical analyses were conducted using independent samples t-test, Mann-Whitney U test, chi-square test or Fisher′s exact test. Results:The age of 524 hospitalized children was five days to 16 years old. Among them, 301(57.4%) were male and 223(42.6%) were female. Additionally, there were 29 critical cases (5.5%) and 495 non-critical cases (94.5%). Critical cases had significantly higher fever peak, more shortness of breath occurrence, more pneumonia and underlying diseases compared to non-critical cases, with statistically significant differences ( t=12.06, χ2=34.90, 10.04 and 31.10, respectively, all P<0.05). Regarding laboratory examinations, critical cases exhibited significantly higher frequencies of decreased lymphocyte count, elevated levels of C-reactive protein, procalcitonin and interleukin-6, abnormal liver function and kidney function, and abnormal creatine kinase isoenzyme compared to non-critical cases, with statistically significant differences ( χ2=8.18, Z=-4.61, Z=-4.28, Z=-5.13, χ2 =195.90, Fisher′s exact test and χ2=136.13, respectively, all P<0.05). Non-critical children cases infected with Omicron variant BA.5 subtype exhibited a higher proportion of symptomatic infections compared to adults. Among children, the occurrence rates of fever and gastrointestinal symptoms (nausea, vomiting, diarrhea) were higher, whereas among adults, the occurrence rate of cough was higher. The differences were statistically significant ( χ2=11.16, 11.83, 8.50 and 28.14, respectively, all P<0.05).From December 1, 2022 to January 20, 2023, a total of 588 children cases and 791 adult cases were collected, while from April 4 to April 30, 2022, a total of 355 children cases and 755 adult cases were collected.In the children group, the occurrence rates of cough, convulsions and critical cases were higher in BA.5 subtype-infected children compared to those infected with the BA.2 subtype, with statistically significant differences ( χ2=37.95, 40.78 and 15.54, respectively, all P<0.001).In the adult group, BA.5 subtype-infected individuals had higher fever peak, longer duration of fever, and higher occurrence of fever, cough and gastrointestinal symptoms, compared to those infected with the BA.2 subtype.The differences were statistically significant ( t=-4.40, Z=-9.64, χ2=47.29, 124.09 and 29.90, respectively, all P<0.001). Conclusions:During the peak periods of BA.5 subtype of the Omicron variant in Shanghai City, critical cases have severe systemic symptoms and a higher prevalence of underlying diseases compared to non-critical cases. Among non-critical cases infected with BA.5 subtype, the proportion of symptomatic infections in children is higher than adults, with fever and gastrointestinal symptoms more common than adults, while cough symptoms are more common seen in adults.The occurrence rate of convulsions and critical cases is higher in children infected with variant BA.5 subtype compared to those infected with BA.2 subtype.The systemic symptoms are more severe in adults infected with BA.5 subtype compared to those infected with BA.2 subtype.

AIM: To compare the changes in axial length of myopic patients of different ages after wearing orthokeratology lenses with increased compression factor(ICF)or conventional compression factor(CCF)for 2 a.METHODS: Retrospective study. A total of 141 myopia patients(141 right eyes)aged 8 to 15 years who fitted with orthokeratology lenses in the General Hospital of Foshan Aier Eye Hospital from July 2020 to July 2021 were continuously included. They were divided into the CCF group(70 cases, 70 eyes)and the ICF group(71 cases, 71 eyes). The patients in the CCF group were fitted with orthokeratology lens of 0.75 DS CCF, while patients in the ICF group were fitted with orthokeratology lens of 1.25 D ICF. Taking 12 years old as a boundary, these two groups were divided into 8-11 years old and 12-15 years old group. The uncorrected visual acuity(UCVA), horizontal corneal curvature(K1)and corneal staining were recorded for all subjects after wearing lenses for 1 d, 1 wk, 1, 6 mo, 1 and 2 a. The axial length(AL)was recorded after wearing lenses for 6 mo, 1 and 2 a, and the complication and corneal epithelial staining were observed during lens wearing.RESULTS:The improvement of UCVA in the ICF group was faster than that in the CCF group, which were statistical significant after wearing lenses for 1 d, 1 wk and 1 mo, respectively(all P<0.001); however, there was no statistical significance between the two groups after 6 mo, 1 and 2 a(all P>0.05); K1 of the ICF group decreased faster than that of the CCF group, and there were statistical significance at 1 d, 1 wk, and 1 mo after wearing lenses(all P<0.05); there was no statistical significance at 6 mo, 1 and 2 a(all P>0.05). The axial length growth of patients aged 8-11 years old in the ICF group and CCF group was 0.35±0.17 and 0.48±0.26 mm, respectively(P=0.010), after wearing lenses for 2 a, and the axial length growth of patients aged 12-15 years old in the ICF group and CCF group was 0.16±0.15 and 0.31±0.29 mm, respectively(P=0.011). During the follow-up period, corneal spotting occurred in 6 eyes(8.5%)in the ICF group, and 7 eyes(10%)in the CCF group(P>0.05), all of which were grade 1 spotting.CONCLUSION:Wearing ICF orthokeratology lens is more effective than wearing CCF lenses in controlling the growth of axial length, with faster shaping and more obvious improvement in UCVA, especially for the prevention of high myopia in children under 12 years. Therefore, young children can give priority to wearing lenses that increase the compression factor, and for children over 12 years old, the compression factor of the lens can be selectively increased according to the wearer's eye habits, health status of ocular surface and visual function.

Chronic myeloid leukemia (CML) with e6a2 transcript type is very rare in clinic,which is usually related to disease aggressiveness. Its clinical characteristics and relationship with tyrosine kinase inhibitor efficacy are still unclear. In this paper, the clinical characteristics and related laboratory tests of a patient with e6a2 fusion gene positive CML characterized by multiple osteolytic bone destruction throughout the body and eosinophil infiltration in gastrointestinal tract, lymph nodes and other organs were retrospectively analyzed, and the relevant literature was reviewed. The patient was Ph chromosome positive with chromosome +8, and the common BCR::ABL1 transcript of CML was negative, but e6a2 transcript was positive detected by RT-PCR. The patient was treated with dasatinib 100 mg/d. Three months later, the patients achieved CHR, CCyR and MR4.0. However, the e6a2 transcript is very rare in clinical practice, and more cases of e6a2 transcript need to be studied to clarify its clinical characteristics and improve the treatment effect of these rare cases.

Objective　To analyze the monitoring data of multidrug-resistant organisms (MDRO) in medical institutions across different regions of Guizhou Province in 2022, and to provide references for the prevention and control of MDRO. 　Methods　Data on the detection rates seven types of MDRO (methicillin-resistant Staphylococcus aurus, vancomycin-resistant Enterococcus faecalis, vancomycin-resistant Enterococcus faecium, carbapenem-resistant Escherichia coli, carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumanni, carbapenem-resistant Pseudomonas aeruginosa) and incidence of hospital-acquired infections in medical institutions across different cities and prefectures of Guizhou Province, 2022 were collected through the monitoring platform of the health network, and the data were analyzed. Results　Data were collected from 223 medical institutions, with an overall detection rate of MDRO of 12.73% (21 931/172 284) and an incidence of hospital-acquired infections of 0.04% (1 969/4 532 711). The detection rate and incidence of hospital-acquired infections of MDRO were different across different regions (χ2=1 871.67, P<0.001; χ2=209.91, P<0.001). The detection rate and incidence of hospital-acquired infections of MDRO in tertiary medical institutions were higher than those in secondary or inferior to secondary medical institutions (χ2=2 095.73, P<0.001; χ2=209.91, P<0.001). The detection rate and incidence of hospital-acquired infections of carbapenem-resistant Acinetobacter baumanni were the highest among MDRO, with 44.87%(5 896/13 139) and 0.015%(658/4 532 711), respectively. Conclusions　The detection rate and incidence of hospital-acquired infections of MDRO in healthcare facilities in Guizhou Province are different, with tertiary medical institutions facing greater pressure for infection control. Relevant medical institutions should focus on the prevalence trend of MDRO in the region, promptly conduct monitoring of MDRO, and take targeted measures to comprehensively prevent and control the spread of MDRO and the occurrence of nosocomial infections.