Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

As a rapidly developing frontier discipline, structural biology has penetrated into every field of life science research. The course of “Structural Biology” plays an important role in expanding the knowledge system of undergraduate students and promoting students’ scientific spirit and innovation. For the high-quality training of highly skilled talents, we aimed to promote the original innovation of students, the ability of thinking, and the ability of engineering practice. The trinity education concept, including shape of the value, passing on knowledge, and ability cultivation, was applied. During the reform, we explored a step-by-step course content and searched for factors involved in ideological and political education. Based on the problem-based learning (PBL) method, a hybrid teaching model was designed to cultivate the problem-thinking and problem-solving skills of students. Meanwhile, a number of evaluation systems for students and teachers were established, which may be generally adopted for the course of “Structural Biology”. The survey data suggested that the exploration has a good effect on teaching and training and is conducive to the cultivation of research-oriented, comprehensive, innovative talents under the background of “New Engineering”.

Objective To investigate the value of unenhanced CT combined with clinical features in predicting adnexal torsion in women with abdominal pain and an adnexal mass. Methods A retrospective selection of patients with abdominal pain and an adnexal mass underwent operation in 2 tertiary hospitals from January 2018 to September 2023. The torsion group (n＝53) and non-torsion group (n＝53) were matched in a 1∶1 ratio. 15 CT signs of adnexal masses were reviewed independently by two radiologists using a double-blind method. The high-risk factors were screened using multivariate logistic regression analysis. The diagnostic values of high-risk factors for adnexal torsion were assessed using receiver operating characteristic (ROC) curves. Results According to the surgical and pathological results, the most common adnexal mass in torsion group was mature cystic teratoma (32.1%), and the most common mass in the non-torsion group was adnexal abscess (20.8%). The age, fever rate, white blood cell count, location of mass, thickened fallopian tube rate, and pelvic effusion rate were not statistically different between the two groups, the nausea and vomiting and remaining CT signs were significant different between the two groups (P＜0.05). Multivariate logistic analysis showed that nausea and vomiting (OR＝4.886), navel sign (OR＝22.733), and whirl sign (OR＝43.462) were independently associated with adnexal torsion (P＜0.05). The area under the curve (AUC) of nausea and vomiting, navel sign, and whirl sign were 0.717, 0.802, and 0.840, respectively; AUC of the combination of all three was 0.877 with 92.45% of sensitivity, 84.91% of specificity, 85.96% of positive predictive value, 91.84% of negative predictive value, and 88.68% of accuracy. Conclusions For women with abdominal pain and an adnexal mass, nausea and vomiting, navel sign, and whirl sign are help of predicting adnexal torsion, and combination value of all three is best.