Ulcerative colitis is a chronic relapsing inflammatory bowel disease. Modern research indicates that immune dysregulation resulting from disruptions in circadian rhythm is closely associated with its pathogenesis. Both Western chronomedicine and traditional Chinese medicine（TCM）" treatment based on temporal factors" emphasize the temporal relationship between natural rhythms and human physiology and pathology. The " midnight-noon and ebb-flow " theory represents the concrete application and deepening of TCM " treatment based on temporal factors" within the realm of chronomedicine. This article correlates the onset time of ulcerative colitis with specific periods in the " midnight-noon and ebb-flow"theory：the Mao period（05：00-07：00），when the yangming large intestine meridian of hand is dominant； the Si period（09：00-11：00），when the taiyin spleen meridian of foot is dominant； and the You period（17：00-19：00），when the shaoyin kidney meridian of foot is dominant. According to this perspective，if the disease manifests during the Mao period，the pathogenesis is attributed to dampnessheat accumulation and disorder of qi and blood. Treatment should focus on clearing heat，resolving dampness，and harmonizing qi and blood，using modified formulas such as Shaoyao Decoction or Baitouweng Decoction. If it occurs during the Si period，the pathogenesis involves spleen deficiency with dampness obstruction and disharmony of qi and blood. Treatment should focus on strengthening the spleen，eliminating dampness，and restoring qi and blood，using modified formulas such as Huangya Decoction or Shenling Baizhu Powder. If it presents during the You period，the pathogenesis is characterized by fire failing to warm earth，and consumption resulting in qi and blood leakage. Treatment should focus on warming the kidney and spleen，and securing qi and blood，using modified formulas such as Sishen Pill or Tianhun Decoction. In addition to oral administration of Chinese herbal medicine，comprehensive therapies including acupuncture，herbal enemas，and acupoint application can provide novel insights for the clinical diagnosis and treatment of ulcerative colitis.

AIM: To explore the clinical application effect of visual training equipment combined with conventional corrective treatment on children with ametropic amblyopia(AMA).METHODS: Prospective randomized control study. A total of 188 children(376 eyes)with AMA treated in our hospital from June 2021 to December 2022 were selected, and they were divided into two groups using a random number table. The conventional correction group(94 cases, 188 eyes)received conventional correction treatment, while the visual training group(94 cases, 188 eyes)received visual training equipment combined with conventional correction treatment, both lasted for 12 mo. The best corrected visual acuity, diopter, eye accommodation function, adverse reactions, amblyopia recurrence rates, and clinical efficacy were compared between the two groups at 6 and 12 mo after treatment.RESULTS:The two groups each had 8 cases(16 eyes)detached, the rate of loss to follow-up was 8.5%, and 86 cases(172 eyes)were included in each group. There were statistically significant differences in the best corrected visual acuity, diopter, amplitude of accommodation, accommodation facility and accommodative lag between the two groups of children before and after treatment(all P<0.05). The total effective rate of the visual training group(98.8%)was higher than that of the conventional correction group(91.9%; P<0.05). There was no statistically significant difference in the total effective rate of clinical efficacy between the two groups in different age groups and different degrees of amblyopia(all P>0.05). There was no statistically significant difference in the incidence of redness and swelling between the two groups(P>0.05). The recurrence rate of amblyopia in the visual training group(1.2%)was lower than that in the conventional correction group(8.1%; P<0.05).CONCLUSION: The combination of visual training equipment and conventional correction therapy has a significant clinical effect on children with AMA, which can effectively correct visual acuity, adjusting diopter and improve eye accommodation function, and recurrence rate of amblyopia is low and safety is high.

Soybean meal (SBM) prepared by soybean crushing is the most popular protein source in the poultry and livestock industries (Cai et al., 2015) due to its economic manufacture, high protein content, and good nutritional value. Despite these benefits, SBM contains various antigen proteins such as glycinin and β-conglycinin, which account for approximately 70% of the total proteins of the SBM and reduce digestibility and damage intestinal function (Peng et al., 2018). Treating SBM with proteases (neutrase, alcalase, and trypsin) or fermentation can eliminate these antigen proteins (Contesini et al., 2018). Because of its safety and rapid growth cycle, Bacillus strains are considered ideal for the fermentation industry (Yao et al., 2021). SBM fermented by Bacillus yields products with high nutritional value and low levels of antinutritional factors (ANFs), stimulating research in this area (Yuan et al., 2017). Kumari et al. (2023) demonstrated that fermentation with Bacillus species effectively degrades antigen proteins and increases crude protein content. The degradation of antigen proteins relies on protease hydrolysis. Low protease production is the major obstacle hindering the widespread use of microbial fermentation techniques.
Bacillus amyloliquefaciens/metabolism* ; Fermentation ; Glycine max/metabolism* ; Soybean Proteins/metabolism* ; Peptide Hydrolases/metabolism* ; Ribosomes/metabolism* ; Globulins ; Antigens, Plant ; Seed Storage Proteins

OBJECTIVES: To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). METHODS: We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. CONCLUSIONS HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.
Animals ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Migraine Disorders/metabolism* ; Disease Models, Animal ; Inflammation

OBJECTIVES: To investigate the mechanisms of Modified Chaihu Guizhi Decoction (MCGD) for ameliorating anxiety- and depression-like behaviors in a mouse model of chronic unpredictable mild stress (CUMS). METHODS: The main chemical constituents of MCGD were identified through literature review, and network pharmacology analysis was performed to predict the potential pharmacological mechanisms of MCGD. For in vivo validation, male C57BL/6J mice were randomized into control group, CUMS model group, fluoxetine (FLX) treatment group, and low- and high-dose MCGD treatment groups (n=15), and in all but the control group, CUMS models were established by daily exposure to two randomized stressors for 28 consecutive days. Starting from 3 days prior to modeling, MCGD and fluoxetine treatments were administered daily via gavage and intraperitoneal injection, respectively. Depression- and anxiety-like behaviors of the mice were assessed using sucrose preference test, forced swim test, open field test and elevated plus maze test. The changes in mRNA expressions of the clock genes and inflammatory markers and expressions of the JAK2/STAT3 signaling proteins were detected using RT-qPCR and Western blotting, and immunofluorescence staining was used to detect microglia activation in the mice. RESULTS: The key active compounds in MCGD identified by network pharmacology analysis included quercetin, acacetin, formononetin, nobiletin, and baicalein. GO analysis identified 607 enriched pathways, and KEGG pathway enrichment revealed significant involvement of the JAK2/STAT3 and NF-κB signaling pathways. In the mouse models of CUMS, treatment with both fluoxetine and MCGD significantly alleviated anxiety- and depression-like behaviors. MCGD treatment significantly reduced Iba1 expression, improved the inflammatory markers, reversed the decrease in clock gene circadian rhythm amplitude, and obviously downregulated the expressions of JAK2, p-STAT3, p-NF-κB, IL-1β, and IL-6 proteins. CONCLUSIONS MCGD effectively alleviates anxiety- and depression-like behaviors in CUMS mice by modulating the inflammatory pathways and inhibiting the JAK2/STAT3 signaling pathway.
Animals ; Janus Kinase 2/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; Mice, Inbred C57BL ; Anxiety/drug therapy* ; Stress, Psychological ; Disease Models, Animal

A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades; the intrinsic link between microbiota and brain function through the microbiota-gut-brain axis or other pathways has gradually been realized. However, little research has focused on viruses-entities characterized by smaller dimensions, simpler structures, greater diversity, and more intricate interactions with their surrounding milieu compared to bacteria. To date, alterations in several populations of bacteriophages and viruses have been documented in both mouse models and patients with psychiatric disorders, including schizophrenia, major depressive disorder, autism spectrum disorder, and Alzheimer's disease, accompanied by metabolic disruptions that may directly or indirectly impact brain function. In addition, eukaryotic virus infection-mediated brain dysfunction provides insights into the psychiatric pathology involving viruses. Efforts towards virus-based diagnostic and therapeutic approaches have primarily been documented. However, limitations due to the lack of large-scale cohort studies, reliability, clinical applicability, and the unclear role of viruses in microbiota interactions pose a challenge for future studies. Nevertheless, it is conceivable that investigations into viruses herald a new era in the field of precise psychiatry.
Humans ; Mental Disorders/virology* ; Animals ; Brain/virology* ; Gastrointestinal Microbiome/physiology* ; Viruses ; Virus Diseases/complications*

Proteolysis-targeting chimeras (PROTACs) represent a promising class of drugs that can target disease-causing proteins more effectively than traditional small molecule inhibitors can, potentially revolutionizing drug discovery and treatment strategies. However, the links between in vitro and in vivo data are poorly understood, hindering a comprehensive understanding of the absorption, distribution, metabolism, and excretion (ADME) of PROTACs. In this work, ¹⁴C-labeled vepdegestrant (ARV-471), which is currently in phase III clinical trials for breast cancer, was synthesized as a model PROTAC to characterize its preclinical ADME properties and simulate its clinical pharmacokinetics (PK) by establishing a physiologically based pharmacokinetics (PBPK) model. For in vitro-in vivo extrapolation (IVIVE), hepatocyte clearance correlated more closely with in vivo rat PK data than liver microsomal clearance did. PBPK models, which were initially developed and validated in rats, accurately simulate ARV-471's PK across fed and fasted states, with parameters within 1.75-fold of the observed values. Human models, informed by in vitro ADME data, closely mirrored postoral dose plasma profiles at 30 mg. Furthermore, no human-specific metabolites were identified in vitro and the metabolic profile of rats could overlap that of humans. This work presents a roadmap for developing future PROTAC medications by elucidating the correlation between in vitro and in vivo characteristics.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Objective:To investigate the predictive value of preoperative 18F-FDG PET/CT imaging for postoperative recurrence and metastasis in patients with stage Ⅰ solid and subsolid non-small cell lung cancer (NSCLC). Methods:This retrospective analysis included 139 patients (71 males, 68 females; age (62.1±9.0) years) with ⅠA1-ⅠB stage solid and subsolid NSCLC who underwent surgery and preoperative 18F-FDG PET/CT imaging at the Fourth Hospital of Hebei Medical University from December 2020 to December 2022. Patients were randomly divided into a training group and a validation group in a ratio of 7∶3, and SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG), clinical data, and disease-free survival (DFS) were collected. ROC curves were generated for the training group to determine the optimal cut-off values of SUV max, MTV, and TLG for predicting recurrence and metastasis. The Cox proportional hazards regression model was used to identify factors predicting DFS and to establish a prediction model, which was then validated in the validation group. The prognostic efficacy of the model was evaluated by using the concordance index (C-index). Results:Of 139 patients, 97 were in the training group and 42 were in the validation group, with 23 experienced recurrences during the follow-up period, including 18 in the training group and 5 in the validation group. The optimal cut-off values of SUV max, MTV and TLG for predicting tumor recurrence and metastasis in the training group were 5.85, 5.55cm 3, and 12.55g, respectively. Univariate analysis showed that SUV max (hazard ratio ( HR)=4.83, 95% CI: 1.81-12.89, P=0.002), MTV ( HR=6.90, 95% CI: 2.27-20.98, P<0.001), and TLG ( HR=5.77, 95% CI: 1.90-17.57, P=0.002) were predictive factors for postoperative recurrence and metastasis, while multivariate analysis identified MTV ( HR=4.67, 95% CI: 1.42-15.36, P=0.011) as an independent predictive factor. The prognostic C-index (95% CI) of models in training group and validation group were 0.814(0.745-0.882) and 0.810(0.624-0.995). Conclusions:Preoperative 18F-FDG PET/CT imaging has significant predictive value for postoperative recurrence and metastasis risk in patients with stage Ⅰ solid and subsolid NSCLC. MTV can be considered as an independent prognostic factor for preoperative recurrence and metastasis.

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.