ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare. Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024. Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse. Conclusion In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare. Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024. Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse. Conclusion In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare. Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024. Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse. Conclusion In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Objective To investigate the clinical efficacy of modified Fuzheng Yiliu Decoction(composed of Astragali Radix,Codonopsis Radix,Ligustri Lucidi Fructus,Hedyotis Diffusae Herba,Moutan Cortex,Visci Herba,etc.)combined with XELOX regimen(Oxaliplatin plus Capecitabine)for the treatment of postoperative patients with advanced gastric cancer of qi and yin deficiency type.Methods A total of 80 postoperative patients with advanced gastric cancer of qi and yin deficiency type were randomly divided into the Chinese medicine group and the control group,with 40 cases in each group.Both groups received chemotherapy with XELOX regimen,while the Chinese medicine group was given modified Fuzheng Yiliu Decoction.Three weeks constituted a course of treatment,the medication of Chinese medicine decoction lasted for two weeks or more in each course of treatment,and a total of 8 courses of treatment were performed.The incidence of adverse reactions during chemotherapy was monitored and changes in serum tumor markers of serum carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and alpha-fetoprotein(AFP)were observed in the two groups before and after treatment.Moreover,the patients'quality of life was assessed by the scores of Karnofsky's Performance Status(KPS)and World Health Organization Quality of Life Measurement Scale(WHOQOL-100).Long-term follow-up was carried out for the evaluation of the prognostic indicators such as overall survival and one-year and 2-year overall survival rates.Results(1)Patients in the two groups were all followed up,and the median follow-up time was 27 months(95%CI:23.59-27.86).(2)After treatment,the levels of serum CEA and AFP in the Chinese medicine group were significantly lower than those before treatment(P＜0.05 or P＜0.01),while serum CA199 tended to decrease compared with those before treatment,but the difference was not statistically significant(P＞0.05);in the control group,the levels of serum CEA,CA199,and AFP were not significantly decreased after treatment(P＞0.05).The intergroup comparison showed that the decrease of serum CEA,CA199 and AFP levels in the Chinese medicine group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)The adverse reactions during chemotherapy in the two groups mainly involved bone marrow suppression,gastrointestinal reactions and liver function abnormalities,etc.The incidences of all adverse reactions in the Chinese medicine group tended to be lower than those in the control group,but the differences were not statistically significant(P＞0.05).(4)After treatment,the KPS scores of patients in both groups were improved compared with those before treatment(P＜0.01),and the improvement in the Chinese medicine group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the scores of the four dimensions of WHOQOL-100 such as health status,mobility,life feelings,and other activities of daily life in the Chinese medicine group were significantly improved compared with the pre-treatment(P＜0.05),whereas there was no significant improvement in the control group(P＞0.05).The intergroup comparison showed that the improvement of the scores of each dimension of the WHOQOL-100 in the Chinese medicine group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(6)The median survival in the Chinese medicine group was 29.0 months(95%CI:25.95-31.70)and that in the control group was 22.0 months(95%CI:19.67-25.58),indicating that the median survival was significantly prolonged in Chinese medicine group(P＜0.01).The one-year and 2-year postoperative survival rates were 97.5%and 77.5%in the Chinese medicine group and 92.5%and 47.5%in the control group,respectively.The intergroup comparison showed that the one-year and 2-year postoperative survival rates in the Chinese medicine group were higher than those in the control group(P＜0.01).Conclusion Modified Fuzheng Yiliu Decoction can effectively alleviate the adverse reactions during adjuvant chemotherapy for postoperative patients with advanced gastric cancer of qi and yin deficiency type,improve the quality of life of patients,and prolong the survival time of patients.

Objective:To explore the early effects and safety of using a hybrid fixation strategy with 3D-printed porous tantalum metal augments to reconstruct substantial bone defects in complex primary total knee arthroplasty (TKA).Methods:A retrospective analysis was performed on the clinical data from August 2019 to September 2023, encompassing 20 patients (21 knees) with significant bone loss who underwent hybrid fixation with 3D-printed porous tantalum augments. The procedures were conducted at two medical centers: the First Affiliated Hospital, School of Medicine, Zhejiang University (11 cases) and Xiangya Hospital of Central South University (9 cases). The study cohort comprised 6 males (6 knees) and 14 females (15 knees), with a mean age of 61.05±11.23 years (range, 42-80 years). The distribution of cases was 7 on the left side and 14 on the right side. All cases were categorized as type 3 according to the Anderson Orthopaedic Research Institute (AORI) classification system. The cohort included 19 unilateral and 1 bilateral case, with 5 involving complex primary replacements (3 with Charcot arthropathy, 1 with syphilitic arthropathy, and 1 with severe valgus deformity) and 16 revision surgeries (13 for aseptic loosening and 3 for infection). Preoperative assessments included routine CT scans and digital three-dimensional reconstructions to identify large metaphyseal defects exceeding 50% of the metaphyseal area or those thicker than 10 mm. For such defects, 3D-printed standardized porous tantalum augments were implemented. In cases of extensive cavitary bone defects or severe metaphyseal defects where the medial and lateral defects collectively exceeded 80% of the metaphyseal region or where the residual bone stock was insufficient for screw fixation of standardized augments, 3D-printed personalized custom-made porous tantalum augments were employed for hybrid fixation and repair. Comparative analyses were conducted on pre- and postoperative imaging data (prosthesis positioning and complications), knee range of motion (ROM), visual analogue scale (VAS) for pain, and Knee Society score (KSS).Results:Of the cases, 17 were repaired using standardized 3D-printed porous tantalum augments, while 4 underwent repairs with customized augments for hybrid fixation. Follow-up averaged 26.5±15.0 months (range, 12-62 months). There was a significant increase in knee ROM, improving from 72.8°±31.9° preoperatively to 113.2°±6.8° at 12 months postoperatively ( P<0.05). VAS scores decreased from 6.6±1.4 preoperatively to 2.5±1.0 at 12 months postoperatively ( P<0.05). Similarly, KSS improved from 52.8±6.4 preoperatively to 80.7±7.9 at 12 months postoperatively ( P<0.05). There were no incidences of prosthesis displacement, poor bone integration, or postoperative infections. Conclusion:The hybrid fixation strategy employing 3D-printed porous tantalum augments has been found to be effective in addressing significant bone defects in TKA. The follow-up results indicate a satisfactory biological integration of the porous tantalum metal augments with the host bone, which has resulted in substantial improvements in pain relief and knee joint functionality.

AIM To study the chemical constituents from the n-butanol fraction of Siegesbeckiae glabrescens Makino.METHODS The n-butanol fraction from S.glabrescens was isolated and purified by silica gel,ODS and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Seventeen compounds were isolated and identified as orientalin B(1),ent-2-oxo-15,16,19-trihydroxypimar-8(14)-ene(2),ent-12α,16-epoxy-2β,15α,19-trihydroxypimar-8-ene(3),ent-12α,16-epoxy-2β,15α,19-trihydroxy-pimar-8(14)-ene(4),kirenol(5),benzyl-O-β-D-glucopyranoside(6),hexyl-β-glucopyranoside(7),(Z)-3-hexenyl-β-D-glucopyranoside(8),phenylethyl-O-β-D-glucopyranoside(9),(6R,9S)-3-oxo-α-ionol-β-D-glucopyranoside(10),2-methoxy-4-(2-propenyl)phenyl-β-D-glucoside(11),4-allyl-2,6-dimethoxyphenyl glucoside(12),2-hydroxy-methylphenyl-1-O-β-D-glucopyranoside(13),icarside B2(14),everlastoside D(15),(2S,4R,5S,7S,9S,10R,13S,15R)-2,7,15,16,19-pentahydroxypimar-8(14)-ene(16),and benzyl-β-D-apiofuranosyl-(1″→6′)-β-D-glucopy-ranoside(17).Compound 9 showed weak ABTS radical scavenging capability,and compound 15 had strong DPPH and ABTS radicals scavenging activities.CONCLUSION Compounds 7-9,14-15 are isolated from genus Siegesbeckia for the first time.Compounds 2-4,7-17 are first isolated from this plant.Compound 9 and 15 exhibit antioxidant activities.

Objective To deeply explore the principles of drug combinations in the treatment of vitiligo by traditional Chinese medicine master XUAN Guo-Wei by data mining technology,and to analyze the potential mechanism of action of the core drug pairs by network pharmacology.Methods The original case records of Professor XUAN Guo-Wei in treating vitiligo were compiled,and then TCM inheritance Computing Platform was used to analyze the frequency of drugs in the prescriptions,the association rules between drugs,and the core combinations of drugs by the association rule method,and the core drug pairs of Professor XUAN Guo-Wei's treatment of vitiligo were obtained based on the results of the data mining,additionally,the mechanism of the core pairs of drugs was analyzed by using the method of network pharmacology.Results A total of 243 prescriptions were collected,among which the high-frequency drugs were Glycyrrhizae Radix et Rhizoma,Tribuli Fructus,Ecliptae Herba,Cuscutae Semen,Scrophulariae Radix,Angelicae Dahuricae Radix,etc.,and the core pair was Tribuli Fructus-Ecliptae Herba.The main components of Tribuli Fructus-Ecliptae Herba for the treatment of vitiligo were quercetin,kaempferol,etc.,there were 47 targets for the intersection of the active ingredients with the disease,among which TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,and IL4 may be the core targets for the treatment of vitiligo by Tribuli Fructus-Ecliptae Herba.The main pathways of Tribuli Fructus-Ecliptae Herba drug pairs against the disease were PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.Conclusion The core drug pair of Professor XUAN Guo-Wei in the treatment of vitiligo is Tribuli Fructus-Ecliptae Herba,which involves targets such as TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,IL4,etc.,Tribuli Fructus-Ecliptae Herba drug pair maybe exert an effect in the treatment of vitiligo through PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.