Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Objective To investigate the capacity of municipal and county-level Centers for Disease Control (CDC) in Shandong Province for γ radionuclides in food as well as gross α and gross β in drinking water, and to provide evidence for strengthening radiological laboratories. Method Data regarding radioactive detection capacity were collected from 16 prefecture-level cities and 136 county-level CDCs. Chi-square test and Fisher's exact tests were used to compare capacity differences across regions and between cities with and without nuclear power plants. Correlation analysis was used to evaluate the spatial equity of gross α and gross β detection capacity for drinking water. Result The detection capacity of gross α and gross β in drinking water varied significantly among counties (χ²=81.026, P<0.001），no significant difference was found between coastal and inland cities (χ²=2.021，P>0.155); Cities with nuclear power plants showed better detection capacity (χ²=20.253，P<0.01). The detection capacity for γ radionuclides in food was primarily concentrated in the prefecture-level cities that host nuclear power plants. Conclusion The overall detection capacity for radioactivity in drinking water was acceptable but spatially uneven. The capacity for monitoring radioactive contamination in food was generally weak. It is necessary to strengthen capacity building at the grassroots level.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Systemic lupus erythematosus （SLE）， a refractory autoimmune disease， is among the dominant diseases where traditional Chinese medicine （TCM） shows advantages in the field of rheumatology and immunology. The China-Japan Friendship Hospital hosted the "46^th Youth Salon on Dominant Diseases （Systemic Lupus Erythematosus）" organized by the China Association of Chinese Medicine， which led to a consensus on "the advantages， challenges， interdisciplinary approaches， and translational achievements of integrated TCM and Western medical approaches in the diagnosis and treatment of SLE." The diagnosis and treatment of SLE currently face several challenges， such as frequent misdiagnosis and missed diagnosis in the early stages， difficulty in achieving treatment targets， multiple side effects from pharmacotherapy， and the lack of management strategies for special populations， all of which hinder the fulfillment of the clinical needs of patients. Integrated TCM and Western medical approaches can improve clinical symptoms such as skin erythema， aversion to cold and cold limbs， fatigue， dry mouth， restlessness， and heat sensation in the palms and soles， thereby improving patients' quality of life. The approaches also help consolidate the efficacy of conventional Western medicine， slow disease progression， reduce relapse rates， address multi-organ involvement， and prevent or treat complications. Additionally， they enhance efficacy and reduce toxicity， prevent the side effects of Western medications， help reduce hormone use， and offer distinct advantages in the individualized intervention of special populations， contributing to the whole-process management of the disease. However， evidence-based medical support for this integrated approach remains limited， and the quality of available evidence is generally low. Common evaluation systems and modern research methodologies should be adopted to clarify the efficacy of TCM in SLE treatment. Efforts should be made to carry out high-quality evidence-based medical research， strengthen the development of fundamental and pharmacological research， and further explain the distinct advantages of TCM in the diagnosis and treatment of SLE. Future efforts should focus on advancing the integration of TCM and modern medicine， incorporating multi-omics technologies， individualized stratification， and other precision medicine concepts， in combination with artificial intelligence. Moreover， interdisciplinary collaboration should be promoted to utilize modern technology in exploring the essence of TCM theories and screening effective formulae， thereby comprehensively improving the diagnosis and treatment of SLE through integrated TCM and Western medical approaches.

Objective:To compare the changes of maximun flow rate and residual urine volume after tension-free vaginal tape(TVT)and trans-obturator tape(TOT)in the treatment of stress urinary incon-tinence in women.Methods:The clinical data of female patients with stress urinary incontinence who underwent transvaginal midsection tension-free urethral suspension in Peking University People's Hospital from January 2022 to January 2024 were retrospectively analyzed.All the patients were followed up 1 month,6 months and 12 months after surgery.Urodynamics were performed to evaluate urethral sphincter function before surgery.At the same time,B-ultrasonography was improved to determine the residual uri-nary volume of the bladder,and urgent incontinence,detrusor weakness and bladder outlet obstruction were excluded,and the diagnosis was clearly stress incontinence.Maximum flow rate and residual urinary volume were measured during follow-up,and combined with the urinary incontinence questionnaire of the International Urinary Incontinence Advisory Committee,the surgical effect was judged to be cured,im-proved or ineffective according to the degree of improvement of urinary leakage symptoms after surgery.Results:A total of 150 female patients with stress urinary incontinence were included in the study,the average age of the patients was(55.12±10.23)years old,and the follow-up time was 12 months.All patients completed postoperative follow-up,of whom 60 underwent TVT and 90 underwent TOT.The overall effective rates(cure+improvement)1,6,and 12 months after surgery in the TVT group were 93.3％(56/60),91.7％(55/60),and 91.7％(55/60),and those in the TOT group were 92.2％(83/90),90.0％(81/90),90.0％(81/90),respectively,and there was no statistical difference be-tween the two groups.The average maximum urinary flow rates 1,6,and 12 months after surgery in the TVT group were(17.21±4.22)mL/s,(18.05±5.33)mL/s,and(18.37±4.92)mL/s,and those in the TOT group were(18.21±5.32)mL/s,(19.05±4.33)mL/s,and(19.27±4.92)mL/s,re-spectively,and there was no statistical difference between the two groups.The mean residual urine volume 1,6,and 12 months after surgery in the TVT group was(13.21±5.22)mL,(18.25±5.33)mL,and(16.37±7.92)mL,and those in the TOT group was(11.21±6.32)mL,(13.05±5.33)mL,and(11.27±5.92)mL,respectively,and there was no statistical difference between the two groups.Compared with preoperative levels,there were no significant differences in the average maximum flow rate and the residual urine volume in both group at 1,6,and 12 months after surgery.Conclusion:Both TVT and TOT are effective in the treatment of stress incontinence,and have no effect on postopera-tive maximum flow rate and residual urine volume.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Objective: This study aims to investigate the anatomical relationship among the nerve roots, intervertebral space, pedicles, and intradural rootlets of the cervical spine for improving operative outcomes and exploring neuroventral decompression approach in posterior endoscopic cervical discectomy (PECD). Methods: Cervical computed tomography myelography imaging data from January 2021 to May 2023 were collected, and the RadiAnt DICOM Viewer Software was employed to conduct multiplane reconstruction. The following parameters were recorded: width of nerve root (WN), nerve root-superior pedicle distance (NSPD), nerve root-inferior pedicle distance (NIPD), and the relationship between the intervertebral space and the nerve root (shoulder, anterior, and axillary). Additionally, the descending angles between the spinal cord and the ventral (VRA) and dorsal (DRA) rootlets were measured. Results: The WN showed a gradual increase from C4 to C7, with measurements notably larger in men compared to women. The NSPD decreased gradually from the C2–3 to the C5–6 levels. However, the NIPD showed an opposite level-related change, notably larger than the NSPD at the C4–5, C5–6, and C7–T1 levels. Furthermore, significant differences in NIPD were observed between different age groups and genders. The incidence of the anterior type exhibited a gradual decrease from the C2–3 to the C5–6 levels. Conversely, the axillary type exhibited an opposite level-related change. Additionally, the VRA and DRA decreased as the level descended, with measurements significantly larger in females. Conclusion A prediction of the positional relationship between the intervertebral space and the nerve root is essential for the direct neuroventral decompression in PECD to avoid damaging the neural structures. The axillary route of the nerve root offers a safer and more effective pathway for performing direct neuroventral decompression compared to the shoulder approach.

Objective:To summarize and discuss the clinical effect of different forms of anterolateral femoral perforator flap in the repair of acute lower extremity lesions based on the theory of damage control orthopaedics (DCO).Methods:The clinical data of 33 patients with acute destructive wounds in the lower limbs admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to December 2022 were retrospectively analyzed. Under the guidance of the DCO theory, the combined injuries were treated through multidisciplinary consultation, and at the same time, first-stage debridement, bone stent restoration, limb blood transport reconstruction, nerve tendon repair and temporary vacuum sealing drainage (VSD) dressing were applied. After the systemic condition was stabilized, the wound was repaired with anterolateral femoral perforator flaps of different forms. The defect area was 8.0 cm×5.0 cm-35.0 cm×25.0 cm, and the donor flap area was closed in one stage in all cases.Results:30 cases of skin flap survived completely after operation, 2 cases had distal partial necrosis, wound healing after dressing change, 1 case had delayed complete necrosis. The follow-up time was 9-25(14.7±5.3)months. 2 patients were treated with the second stage of repair surgery due to the bloated flap. The rest were satisfied with the shape of the reconstructed flap and the donor flap area, and the ankle joint function score was good.Conclusions:DCO theory combined with anterolateral femoral perforator flap is a safe and effective way to repair the mutilated wounds of lower limbs.