ObjectiveTo investigate the effects of Simiaowan on intestinal barrier function and adenosine triphosphate （ATP） binding cassette transporter G2 （ABCG2） expression in hyperuricemic （HUA） rats， and elucidate its therapeutic mechanisms. MethodsForty male Sprague Dawley （SD） rats were randomized into a normal group， a model group， low-dose （282.6 mg·kg^-1） and high-dose （565.2 mg·kg^-1） Simiaowan groups， and a Benzbromarone （4.7 mg·kg^-1） group. The HUA model was established via intraperitoneal injection of potassium oxonate （ip） combined with oral gavage of hypoxanthine （ig） for 14 days. Following modeling， treatments were administered for 14 days. Samples were collected and weighed 4 h after final dosing. Blood uric acid and hepatic function were analyzed. Histopathological changes were evaluated by hematoxylin-eosin （HE） staining， and Chiu's scoring was conducted. Enzyme-linked immunosorbent assay （ELISA） quantified tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， diamine oxidase （DAO）， and D-lactic acid （D-LA） levels. Real-time polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry assessed the expression of Claudin-1， Occludin， occludens-1 （ZO-1）， and ABCG2 mRNAs and proteins. 16S rDNA amplicon sequencing characterized ileal microbiota. ResultsCompared with the normal group， the model group exhibited epithelial shedding in the ileal villus， structural disruption， infiltration of extensive inflammatory cells， and significantly elevated Chiu's scores （P<0.01）. The DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum were markedly increased （P<0.01）， while mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion， were significantly reduced （P<0.01）. Compared with the model group， the Simiaowan groups at all doses showed improved epithelial damage in the ileal villus， significantly lowered Chiu's scores （P<0.01）， significantly reduced DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum （P<0.01）， and upregulated mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion （P<0.01）. The 16S rDNA results showed that in the model group， the α-diversity index of the ileal microbiota was increased， and species diversity and richness were enhanced， with microbiota dysfunction observed. The community structure of the gut microbiota was significantly different from that of the normal microbiota. The abundance of probiotics was decreased， and the abundance of pathogenic bacteria was increased， with butyrate-producing bacteria showing a low abundance. In contrast， Simiaowan at all doses reduced species diversity and richness， regulated microbiota dysfunction， and promoted the shift of the structure of the gut microbiota community towards a normal one. This increased the abundance of beneficial bacteria， decreased the abundance of harmful bacteria， and restored the abundance of butyrate-producing bacteria. ConclusionSimiaowan enhances ileal uric acid excretion and further alleviates HUA by modulating the gut microbiota composition to improve the intestinal barrier and upregulate the expression of the urate transporter ABCG2 in HUA rats.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

Ecological cultivation is an important way for the sustainable production of traditional Chinese medicine in the context of the carbon peaking and carbon neutrality goals. Facility cultivation and simulative habitat cultivation modes have been developed and applied to develop the endangered Dendrobium huoshanense on the basis of protection. However, the differences in the greenhouse gas emissions and global warming potential of these cultivation modes remain unexplored, which limits the accurate assessment of carbon-friendly ecological cultivation modes of D. huoshanense. Greenhouse gas emission flux monitoring based on the static chamber method provides an effective way to solve this problem. Therefore, this study conducted a field experiment in the facility cultivation and simulative habitat cultivation modes at a D. huoshanense cultivation base in Dabie Mountains, Anhui Province. From April 2023 to March 2024, samples of greenhouse gases were collected every month, and the concentrations of CO_2, CH_4, and N_2O of the samples were then detected by gas chromatography. The greenhouse gas emission fluxes, cumulative emissions, and global warming potential were further calculated, and the following results were obtained.(1)The two cultivation modes of D. huoshanense showed significant differences in greenhouse gas emission fluxes, especially the CO_2 emission flux, with a pattern of facility cultivation>simulative habitat cultivation [(35.60±11.70)mg·m~(-2)·h~(-1) vs(2.10±4.59)mg·m~(-2)·h~(-1)].(2) The annual cumulative CO_2 emission flux in the case of facility cultivation was significantly higher than that of simulative habitat cultivation[(3 077.00±842.00)kg·hm~(-2) vs(221.00±332.00)kg·hm~(-2)], while no significant difference was found in annual cumulative CH_4 and N_2O emission fluxes.(3) The facility cultivation mode had a significantly higher global warming potential than the simulative habitat cultivation mode [(3 053.00±847.00)kg·hm~(-2) vs(196.00±362.00)kg·hm~(-2)]. Overall, the simulative habitat cultivation of D. huoshanense has obvious carbon-friendly characteristics compared with facility cultivation, which is in line with the concept of ecological cultivation of medicinal plants. This study is of great reference significance for the implementation and promotion of the ecological cultivation mode of D. huoshanense under carbon peaking and carbon neutrality goals.
Dendrobium/chemistry* ; Greenhouse Gases/metabolism* ; Carbon/analysis* ; Ecosystem ; Carbon Dioxide/metabolism* ; China ; Global Warming

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Objective:To investigate the relationship between the severity of pharyngolaryngeal sensory impairment and swallowing biomechanics as well as the risk of penetration-aspiration in patients with dysphagia following infratentorial stroke.Methods:This retrospective cross-sectional study enrolled 51 patients with dysphagia following infratentorial stroke hospitalized in the Department of Rehabilitation Medicine of The Third Affiliated Hospital of Sun Yat-sen University between January 2022 and December 2023. Participants were categorized into three groups: normal sensation group [15 males, 2 females; age range 29-76 (56.0±13.3)years], diminished sensation group[16 males, 3 females; age range 38-80(62.0±11.8)years], and absent sensation group [14 males, 1 female; age range 44-75 (60.0±9.7)years]. All patients underwent laryngoscopy and videofluoroscopic swallowing study, which included pharyngolaryngeal sensory testing and Penetration-Aspiration Scale assessment. Swallowing temporal parameters were quantitatively analyzed. Group comparisons for different variable types were conducted using the Chi-square test, one-way ANOVA, and the Kruskal-Wallis test. The correlation between sensory groups and Penetration-Aspiration Scale scores was assessed using Spearman′s correlation analysis. Logistic regression was employed to analyze the impact of pharyngolaryngeal sensory function on penetration-aspiration events.Results:Among the 51 patients, 33.33% (17/51) had normal pharyngolaryngeal sensation, while, 66.67% (34/51) exhibited sensory impairment. The normal sensation group exhibited a significantly longer laryngeal vestibule closure (LVC) time [792 (643, 1 205) ms] compared to the diminished [528 (380, 776) ms] and absent sensation groups [380 (322, 404) ms] ( H=6.502, P=0.039). Additionally, the upper esophageal sphincter opening time was longer in the normal sensation group than in the absent sensation group [528 (371, 710) ms vs 182 (0, 710) ms, H=6.003, P=0.049]. Correlation analysis indicated a significant negative correlation between the severity of sensory impairment and Penetration-Aspiration Scale scores ( r=-0.366, P=0.008). Logistic regression analysis demonstrated that greater sensory impairment was an independent risk factor for penetration-aspiration ( OR=9.29, 95%CI=1.57-54.77, P=0.014). Conclusion:Pharyngolaryngeal sensory deficits are common after infratentorial stroke dysphagia and are significantly associated with impaired swallowing biomechanics and increased aspiration risk. The severity of sensory deficit is a key determinant of penetration-aspiration risk, highlighting its value in risk stratification and therapeutic decision-making for dysphagia.

Many female patients with inflammatory bowel disease (IBD) are of reproductive age, and addressing fertility-related issues is an important part of comprehensive treatment. Although the fertility of female IBD patients does not differ significantly from that of the general population, many women with IBD opt for childlessness. This voluntary childlessness may stem from concerns about the adverse effects of IBD and its treatment on fertility, pregnancy, and newborns. A lack of in depth understanding of fertility, socioeconomic status, demographic factors, and insufficient professional medical advice may also contribute to patients' decision to choose voluntary childlessness. This article analyzes the factors influencing voluntary childlessness in female IBD patients and summarizes recommendations aimed at reducing trend, to enhance fertility awareness among female IBD patients and providing useful references for developing reasonable fertility plans.

Regarding the challenge of early identification of critically ill patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),a radiomics-clinical fusion model is proposed based on non-contrast CT images of accessory respiratory muscles to predict life-threatening conditions.A retrospective study is conducted involving 233 AECOPD patients(153 non-life-threatening and 80 life-threatening cases).Patients are divided into a training set(n=186)and a test set(n=47)at a 4:1 ratio.A total of 1 874 radiomic features are extracted from the erector spinae and pectoralis muscle regions delineated by radiologists on non-contrast CT images,and the features selection is performed using maximum relevance minimum redundancy and least absolute shrinkage and selection operator(LASSO)algorithms.Meanwhile,clinical data are analyzed with t-test and LASSO for variable screening.The selected features are input into C-support vector classification,Logistic regression,random forest,adaptive boosting(AdaBoost),and extreme gradient boosting(XGBoost)to construct radiomics model,clinical model,and fusion model.Predictive performance and clinical practicality are evaluated in the test set using receiver operating characteristic curve,area under the curve(AUC),and decision curve analysis.The radiomics-clinical fusion model built with XGBoost outperformed standalone radiomics and clinical models,achieving an AUC of 0.902(95％CI 0.846,0.994),with accuracy,sensitivity,specificity,and precision of 0.837,0.933,0.786,and 0.7,respectively.Results demonstrate that the fusion model based on the non-contrast CT radiomics of accessory respiratory muscles and clinical data exhibits promising diagnostic performance,highlighting its potential clinical significance for stratified management and preemptive critical care intervention in AECOPD patients.

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

Objective To observe the clinical efficacy of Fangxiang Wentong Powder(composed of Salviae Miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Alpiniae Officinarum Rhizoma,Piper Longum,and Corydalis Rhizoma)acupoint application combined with Kuanxiong Aerosol in treating female patients with coronary slow flow(CSF)associated angina.Methods After sample size estimation,119 female inpatients diagnosed as CSF associated angina and differentiated as chest-qi obstruction with yang deficiency and cold accumulation syndrome of traditional Chinese medicine(TCM)were collected from the cardiovascular departments of the Third People's Hospital of Fujian University of Traditional Chinese Medicine,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine),Zhanjiang First Traditional Chinese Medicine Hospital,and Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2023 to March 2024.Using a table of random numbers,the patients were divided into a treatment group(84 cases)and a control group(35 cases)in a ratio of 5∶2.The control group was treated with Isosorbide Monomitrate Sustained-Release Capsules,while the treatment group was treated with application of Fangxiang Wentong Powder on acupoints of Danzhong(CV17),Gaohuang(BL43),and Xinshu(BL15),together with sublingual administration of Kuanxiong Aerosol.The treatment course for both groups covered 7 days.Before and after treatment,the changes in the simplified Seattle Angina Questionnaire(SAQ-7)scores,Chinese Quality of Life Questionnaire for Cardiovascular Patients(CQQC)scores,6-minute walking distance(6MWD),serum C-reactive protein(CRP)level,and white blood cell-to-mean platelet volume ratio(WMR)were observed.The TCM symptom efficacy was compared between the two groups,and adverse reactions were monitored.Results(1)There were 8 patients withdrew in the treatment group for failing in completing the questionnaires,and 2 patients withdrew in the control group for suffering headaches after taking nitrates.Eventually,109 patients completed the trial,including 76 in the treatment group and 33 in the control group.(2)After 7 days of treatment,the total effective rate for TCM symptom efficacy in the treatment group was 86.84%(66/76),and that in the control group was 72.73%(24/33).The intergroup comparison(tested by the chi-square test)showed that the TCM symptom efficacy in the treatment group was significantly superior to that in the control group.(3)After treatment,both groups showed improvements in the scores of activity limitation and angina frequency items of SAQ-7,and the treatment group also showed improvements in the scores of subjective satisfaction item of SAQ-7(P＜0.05).The treatment group's improvements in the scores of activity limitation,angina frequency,and subjective satisfaction items of SAQ-7 were significantly superior to those of the control group(P＜0.05).(4)After treatment,the CQQC scores in the treatment group was significantly improved(P＜0.05),while no significant improvement was observed in the control group(P＞0.05).The improvement of CQQC scores in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,both groups showed improvements in 6MWD(P＜0.05),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05).(6)After treatment,the serum levels of inflammatory indicators of CRP and WMR in the treatment group were significantly improved(P＜0.05),while no significant improvements were presented in the control group(P＞0.05).The improvements in serum CRP level and WMR value in the treatment group were significantly superior to those in the control group(P＜0.05).(7)No adverse reactions were found in the treatment group,indicating high safety.Conclusion Fangxiang Wentong Powder acupoint application combined with Kuanxiong Aerosol is more effective than Isosorbide Monomitrate Sustained-Release Capsules,improving exercise tolerance,decreasing inflammatory factor levels,and improving the quality of life to some extent during the treatment of female patients with CSF.