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.

As an important strategy in antiviral drug development, nucleoside analogs (NAs) have attracted considerable attention due to their unique mechanisms of action and favorable safety profile. This review systematically summarizes recent advances in the mechanisms of action of NAs, focusing on the following four aspects: (1) Targeting viral polymerases, inhibiting viral replication through mechanisms such as non-absolute termination, delayed chain termination and induction of viral RNA mutations in addition to classical chain termination, which has been newly discovered; (2) Regulating RNA methylation modifications—for instance, competitively inhibiting methyltransferases, which significantly reduces viral replication efficiency; (3) Depleting nucleotide pools—by affecting host cell purine nucleotide synthesis pathways, thereby indirectly inhibiting viral replication; and (4) Immunomodulatory functions—including activation of the STING pathway to promote interferon production. Furthermore, this review systematically discusses the breakthrough progress in prodrug technologies for addressing key clinical challenges such as drug resistance and off-target toxicity of NAs. These advances provide crucial technical support for the clinical translation of NAs. These advances provide key technical support for the clinical translation of NAs. This review clarifies the multi-target action rules of NAs and provides a theoretical framework for the design of next-generation broad-spectrum antiviral agents.

Colitis is a common intestinal disease characterized by a chronic course, impaired quality of life and poor prognosis. Due to the anatomical specificity of the colon, the development of targeted and efficient drug delivery systems has become a research focus. With the rapid development of nanotechnology, nano drug delivery systems have been widely used in colitis treatment owing to their ease of preparation, controllable quality and excellent targeting capability. In this review, the general situation of colitis was summarized. Based on the classification of drug delivery carriers of different materials, the application progress of organic polymers, inorganic materials, biological and metallic nano drug delivery systems in colitis therapy was introduced. The potential of these four types of nano drug delivery systems was summarized and analyzed.

Biomineralization is a unique process for generating biominerals and has become a popular area of research in biomedical materials due to its excellent biocompatibility and biodegradability, as well as the simple and economical synthesis process. In this review, the fundamental concepts of biomineralization and the principles of organic matrix-induced nucleation were introduced. According to the biomimetic mineralization technology mediated by matrices such as proteins and their derivatives, nucleic acids, nanozymes, polysaccharides, organisms, polymers and metal-organic frameworks, the application progress of biomineralization technology to drug delivery by protecting active molecules, constructing drug carriers and responding to acidic environments was reviewed. The difficult problems to be solved were also summarized.

Objective:To investigate the clinical efficacy of intraoperative regional lymph-adenectomy and extended lymphadenectomy in resectable hilar cholangiocarcinoma.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 187 patients of hilar cholangiocarcinoma who were admitted to Henan University People′s Hospital from January 2014 to January 2018 were collected. There were 105 males and 82 females, aged (57±9)years. Of the 187 patients, 62 patients undergoing hilar cholangiocarcinoma resection with extended lymphadenectomy were divided into the extended group, and 125 patients under-going hilar cholangiocarcinoma resection with regional lymphadenectomy were divided into the regional group. Observation indicators:(1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) follow-up. Comparison of measurement data with normal distribu-tion between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. The Kaplan-Meier method was used to plot calculate survival rate and survival curve. The Log-rank test was used for survival analysis. Propen-sity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.1. Results:(1) Propen-sity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 187 patients, 104 patients were success-fully matched, with 52 cases in each of the extended group and the regional group. After propensity score matching, the elimination of tumor diameter, neural invasion, Bismuth classification, and TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After pro-pensity score matching, the operation time of the extended group was (341±83)minutes, the number of lymph node dissected was 12.3±4.5, the number of positive lymph node dissected was 2.2±0.7, cases of postoperative new lymphadenectasis was 17. The above indicators of the regional group were (311±73)minutes, 9.2±3.4, 1.5±0.5, 44, respectively. There were significant differences in the above indica-tors between patients of the two groups ( t=-1.99, -3.92, -5.57, χ2=31.18, P<0.05). (3) Follow-up. After propensity score matching, all 104 patients were followed up after surgery, with the follow-up time of 29(range, 3-49)months. The postoperative 3-year overall survival rate was 44.2% of the extended group, versus 30.8% of the regional group, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusions:The perioperative safety of regional lymphadenec-tomy and extended lymphadenectomy in the radical resection of hilar cholangiocarcinoma are com-parable. Extended lymphadenectomy can increase the number of positive lymph node detected and improve the postoperative survival rate of patients.

OBJECTIVE To explore the clinical characteristics of Mycoplasma pneumoniae pneumonia(MPP)after COVID-19 epidemic so as to offer help for early clinical diagnosis and treatment.METHODS The clinical data that were collected from the MPP patients who were treated in the fever clinic of the First Medical Center of Chinese PLA General Hospital from Jul.2023 to Aug.2024 were retrospectively analyzed.The results of laboratory tests for the different age groups of patients complicated with other pathogens were statistically analyzed.RESULTS Of totally 161 MPP patients who were enrolled in the study,78(48.85％)were male,and 83(51.55％)were fe-male;the average age was(32.98±14.35)years old,and the patients aged between 20 and 40 years old accoun-ted for 43.48％(70 cases).The enrolled patients were divided into the simple MPP group with 92(57.14％)ca-ses and the MPP+mixed group with 69(42.86％)cases according to the result of etiological test of sputum;the patients of MPP+mixed group were divided into the MPP+bacteria group with 42(60.87％)cases,the MPP+fungi group with 10(14.49％)cases,and the MPP+viruses group with 17(24.64％)cases.There was significant difference in the age among the groups(P＜0.05);there were no significant differences in the sex,white blood cell counts and percentage of mononuclear cells among the groups,the percentage of lymphocytes was highest in the simple MPP group,the levels of C-reactive protein(CRP)and interleukin-6(IL-6)were highest in the MPP+bacteria group,and there were significant differences(P＜0.05).All of the patients were divided into three groups:the ≤20-year-old group the＞20-40-year old group and the＞40-year-old group.There were no sig-nificant differences in the white blood cell counts,percentage of lymphocytes,percentage of mononuclear cells and IL-6 level among the three groups,and the CRP level was highest in the＞20-40-year old group(P=0.025).Ran-dom forest model analysis showed that the weight of CRP was highest(22.65％)among the clinical characteristics of the MPP patients,which played a key role in construction of model.As for other factors,the weight of age was 17.02％,the percentage of lymphocytes 15.34％,the white blood cells counts 14.86％,the percentage of mono-nuclear cells 14.39％,the IL-6 13.61％,the gender 2.13％.CONCLUSION MPP maintains common among the patients aged less than 40 years old after the COVID-19 epidemic,nearly half of the patients are complicated with the infections of other pathogens,and CRP is more helpful for the clinical diagnosis and treatment of the MPP in early stage.

OBJECTIVE To summarize the clinical characteristics and diagnosis and treatment experiences in dealing with non-severe Chlamydia psittaci pneumonia.METHODS The clinical data were collected from 34 patients who were diagnosed with non-severe C.psittaci pneumonia through quantitative polymerase chain reactiong(qPCR)for sputum in fever clinic of the First Medical Center of Chinese PLA General Hospital from Mar.2023 to Mar.2024 and were retrospectively analyzed.The clinical characteristics and treatment outcomes were evaluated.RESULTS The average age of the patients was(44.82±13.74)years old,the ratio of male to female was 1∶1.83;all of the patients had fever;major symptoms were cough(70.59％),pharyngodynia(44.12％),and flu-like symptoms(41.18％);82.35％of the patients had the history of contact with poultry.The C-reactive pro-tein(CRP)level,interleukin-6(IL-6),systemic inflammatory response index(SIRI)and aggregate index of sys-temic inflammation(AISI)were higher among the patients aged no less than 44 years old than among the patients less than 44 years old(P＜0.05);the percentage of lymphocytes of the patients aged no less than 44 years old was lower than that of the patients aged less than 44 years old(P＜0.05).As for the imaging findings,73.53％of the patients had consolidation shadows,26.47％had ground-glass opacities,and 32.35％involved both lungs.All of the patients received quinolones or tetracyclines for treatment of 7-14 days and all symptoms relieved.CT reexami-nated 1 month after the treatment showed that 55.88％of the cases had complete absorption of pulmonary infec-tious lesions,and 35.29％had partial absorption.CONCLUSIONS The patients with non-severe Chlamydia psitta-ci pneumonia are characterized by the history of contact with poultry,fever complicated with respiratory tract symptoms,rise of inflammatory markers(more significant among patients of advanced age)and lower lobe con-solidation shadow/ground-glass opacities.Early identification and standardized treatment may facilitate the favora-ble treatment outcomes.

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

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.

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