OBJECTIVES: To evaluate the clinical efficacy of hospital-prepared Chinese medicine Feigan granules for influenza patients. This study has been registered at the International Traditional Medicine Clinical Trial Registry platform (ITMCTR2025000162). METHODS: A prospective observational study was conducted on influenza patients who visited the Fever Clinic of the First Affiliated Hospital, Zhejiang University School of Medicine between February and March 2024. Patients were divided into the observation group (Feigan granules combined with conventional Western medicine) and the control group (conventional Western medicine). Main symptoms (including fever, cough and sore throat) and secondary symptoms (including chest tightness, poor appetite, muscle soreness and dry mouth) were evaluated with traditional Chinese medicine (TCM) symptom scale on the first day of the patient's visit and the third day after treatment. The degrees of improvement in the TCM symptom scores before and after treatment were compared using paired rank-sum test, and the differences in the overall symptom efficacy index between two groups were compared using the Wilcoxon test. RESULTS: A total of 217 influenza patients were included. After treatment, the TCM symptom scores of both groups were significantly improved compared with those before treatment (all P<0.01). The median differences in the main symptom score before and after treatment in the observation and the control groups were 7 points (95%CI: 6.0-8.0) and 6 points (95%CI: 6.0-8.0), respectively. The median difference in the secondary symptom score was 3 points (95%CI: 2.0-4.0) in both groups. The median differences in the total score were 9 points (95%CI: 8.0-10.5) and 8 points (95%CI: 7.0-10.0) in the observation and control groups, respectively. In the subgroup with an initial cough score >2, the improvement rates of total score (97.06% vs. 92.59%) and secondary symptoms (92.31% vs. 85.11%) in observation group were significantly higher than those in the control group (P<0.05); while there was no significant difference in the improvement rate of the main symptoms (95.59% vs. 90.74%, P>0.05). CONCLUSIONS Feigan granules can improve the TCM syndromes of influenza patients, especially for patients with more severe cough.
Humans ; Prospective Studies ; Influenza, Human/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Male ; Middle Aged ; Adult ; Aged ; Adolescent ; Young Adult ; Treatment Outcome

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Aim To investigate the relationship between fibrinogen(FIB)and the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus(T2DM).Methods Hospitalized T2DM patients who underwent two or more coronary CT angiography(CCTA)examinations in the First Affiliated Hospital of Xi'an Jiaotong U-niversity from January 2015 to December 2020 were included.The subjects were divided into high FIB and low FIB groups according to the median of FIB.The differences in the progression of coronary plaque stenosis rate and other clini-cal characteristics were compared between the two groups,and the relationship between FIB level and the progression of coronary plaque stenosis rate was analyzed by Spearman's correlation analysis and Logistic regression.Results A total of 145 patients were included,73 in the high FIB group and 72 in the low FIB group at baseline,with a median follow-up time of 25(18,40)months between CCTA.The age,proportion of women,and the progression of coronary plaque ste-nosis rate were higher in the high FIB group than those in the low FIB group,and the differences were statistically signifi-cant(P＜0.05).FIB level was positively correlated with the change in coronary plaque stenosis rate(r2=0.308,P＜0.001).Multivariate Logistic regression analysis showed that FIB level was a risk factor for the progression of coronary plaque stenosis rate in patients with T2DM(OR=5.25,95％CI:1.97～14.02,P＜0.001),after adjusting for age,sex and other clinical risk factors.Conclusion High baseline FIB level is an independent risk factor for the progression of coronary plaque stenosis rate in patients with T2DM,and monitoring FIB level is beneficial to cardiovascular risk stratifica-tion in patients with T2DM.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

Objective: To investigate the preliminary screening results of Alzheimer's disease (AD) among the elderly in Ningbo City, Zhejiang Province and analyze the influencing factors, so as to provide insights into prevention and control of AD in the elderly. Methods: A multi-stage stratified proportional sampling method was used to select the registered residents aged 60 years and older in Ningbo City as subjects. Demographic characteristics, lifestyle factors, physical conditions and social activities of the subjects was evaluated with questionnaires. AD was screened using the Mini-Mental State Examination (MMSE), and factors affecting the positive rate of AD preliminary screening were identified using a multivariable logistic regression model. Results: A total of 34 027 elderly residents were investigated, with an mean age of (71.71±6.89) years. There were 15 115 males (44.42%) and 18 912 females (55.58%), 16 146 residents living in rural areas (47.45%) and 17 881 residents living in urban areas (52.55%). The positive rate of AD preliminary screening was 7.28% (2 476 cases). Multivariable logistic regression analysis showed that age (70 to 74 years, OR=1.357; 75 to 79 years, OR=1.807; 80 to 84 years, OR=2.782; 85 years and older, OR=4.907), gender (female, OR=1.118), residence (urban areas, OR=0.713), marital status (unmarried, OR=3.078; widowed/separated/divorced, OR=1.301), educational level (primary school, OR=0.629; junior high school and above, OR=0.609), occupation before retirement (others, OR=0.741), family genetic history (no, OR=0.651), household disposable monthly income (1 000 to 1 999 Yuan, OR=0.636; 2 000 to 2 999 Yuan, OR=0.569; 3 000 Yuan and above, OR=0.448), exercise (seldom, OR=0.855; regular, OR=0.780), number of chronic diseases (2~5, OR=1.328), hearing loss (no, OR=0.764), smell loss (no, OR=0.615), chronic constipation (no, OR=0.696), major negative life events (no, OR=0.804), subjective memory loss (no, OR=0.583), sleep quality (general, OR=0.640; good, OR=0.616), living style (living with spouse, OR=0.300; living alone, OR=0.315; living with children, OR=0.350) and social activities (2-3 times/week, OR=0.584; 4 times/week and more, OR=0.409) were factors affecting the positive rate of AD preliminary screening. Conclusions The positive rate of AD preliminary screening among the elderly in Ningbo City is relatively high. Age, gender, economic conditions, exercise, social activities and physical conditions were factors affecting the positive rate of AD preliminary screening.

Objective:To investigate the efficacy of tandospirone combined with venlafaxine in the treatment of comorbid anxiety and depression and its effects on neurotransmitters and related factors.Methods:A total of 92 patients with comorbid anxiety and depression who received treatment in the Second People's Hospital of Lishui between June 2019 and June 2020 were included in this study. They were randomly divided into an observation group and a control group ( n = 46/group). The control group was treated with venlafaxine, while the observation group was treated with tandospirone and venlafaxine. Before and after treatment, the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), the levels of 5-hydroxytryptamine, brain-derived neurotrophic factor, nerve growth factor, and adverse drug reactions were compared between the two groups. Results:At 4 and 8 weeks after treatment, HAMA scores in the observation group were (11.39 ± 3.11) points and (8.26 ± 2.18) points, respectively, which were significantly lower than (14.72 ± 3.57) points and (10.46 ± 2.37) points in the control group ( t = 4.77, 4.63, both P < 0.05). At 4 and 8 weeks after treatment, HAMD scores in the observation group were (15.95 ± 2.90) points and (9.33 ± 1.54) points, respectively, which were significantly lower than (17.43 ± 2.87) points and (13.28 ± 2.65) points in the control group ( t = 2.46, 8.74, both P < 0.05). After treatment, 5-hydroxytryptamine, nerve growth factor, and brain-derived neurotrophic factor levels in the observation group were (154.59 ± 45.26) μg/L, (13.62 ± 1.16) ng/L, (28.54 ± 2.33) ng/L, respectively, which were significantly higher than (129.99 ± 48.31) μg/L, (11.98 ± 1.04) ng/L, and (25.69 ± 2.51) ng/L in the control group ( t = 2.52, 7.14, 5.64, all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( χ2 = 0.81, P = 0.369). Conclusion:The adjuvant treatment with tandospirone can markedly improve anxiety and depression and protect neurological function of patients with comorbid anxiety and depression, and is highly safe.

Objective:To explore the clinical efficacy of lenalidomide combined with second-line immunochemotherapy as a salvage regimen in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 37 relapsed/refractory DLBCL patients receiving lenalidomide combined with second-line immunochemotherapy as a salvage regimen who had recurrence after autologous hematopoietic stem cell transplantation or who were not eligible for transplantation or had no intention to transplant between January 2016 and December 2020 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. Among 37 patients, 6 cases with primary central nervous system (CNS) lymphoma and 3 cases with secondary CNS lymphoma. The short-term efficacy after treatment was evaluated. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS), and log-rank test was used for subgroup comparison.Results:The median follow-up time of 37 patients was 20.4 months (2.7-37.0 months). At the end of treatment, the overall response rate (ORR) of all patients was 64.9% (24/37), the complete response (CR) rate was 45.9% (17/37), and the median duration of response (DOR) of 24 patients who responded to treatment was 17.7 months (3.6-33.6 months). The median PFS time of all patients was 11.2 months, and the 1-year PFS rate was 48.6% (95% CI 32.5%-64.7%). The median OS time of all patients was not reached, and the 1-year OS was 67.6% (95% CI 52.5%-82.7%). Among 24 responding patients, 17 cases who received lenalidomide maintenance therapy after remission tended to have a better response compared with 7 cases who did not receive lenalidomide maintenance therapy after remission, although there was no significant difference in OS and PFS between both groups (both P > 0.05). Additionally, neutropenia was the most common adverse reaction with an incidence of 81.1% (30/37). Conclusions:Lenalidomide combined with the second-line immunochemotherapy may be an effective salvage therapy for patients with relapsed/refractory DLBCL, especially for patients with CNS involvement. The patients achieving remission after salvage therapy continue to receive lenalidomide maintenance therapy and could have a better prognosis.

Objective:To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS).Methods:This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration.Results:(1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant ( P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups ( P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion:The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

Objective:To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) .Methods:This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle.Results:In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion:The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.