1.Screening and identification of heteroresistant Streptococcus isolates from dairy cows to gentamicin and investigation of their resistance mechanism
Jiaojiao GAO ; Xiaolan HE ; Nan ZHENG ; Xiaowei XU ; Wei SHAO ; Yankun ZHAO
Chinese Journal of Veterinary Science 2025;45(10):2170-2178
This study investigated the prevalence and potential mechanisms of gentamicin heterore-sistance in Streptococcus isolates from dairy cows.In this study,A total of 39 Streptococcus isola-ted from raw milk were collected,and the minimum inhibitory concentration(MIC)of gentamicin and other drugs on the isolates was determined by micro broth dilution method,and the K-B paper diffusion method,colony analysis profile(PAP),and resistance stability test were used to investigate the heteroresistance characteristics of Streptococcus,and the mechanism of heteroresis-tance was analyzed based on whole genome sequencing and resequencing.Seven suspected heterore-sistance strains were identified by K-B paper diffusion method,accounting for 17.95%(7/39)of the total number of suspected strains.PAP confirmed that the MIC to MNIC ratio of L147,L108 and L174 was greater than 8,and the frequency of resistant subgroups ranged from 1.38×10-5 to 8.18 × 10-5,which was greater than 1 × 10-7,confirming that they were heteroresistance strains.Resistance stability tests revealed that the resistant subpopulations of all three strains were not stably inherited.Whole-genome sequencing revealed mutations in the ribosomal target genes of aminoglycoside antibiotics,rsmA,rsmB and rsmE,compared with the reference genome,which may lead to heteroresistance to gentamicin in Streptococcus.The occurrence of heteroresistance of Streptococcus to gentamicin is high in dairy sources,so more attention should be paid to the occur-rence of heteroresistance when using gentamicin for clinical treatment.
2.Validity and reliability of the Chinese version of the Transgender Attitudes and Beliefs Scale in adults
Zhanqiang WANG ; Hanwen DONG ; Yueqian ZHANG ; Xiaolan DI ; Kebing YANG ; Rongjiang ZHAO ; Qingtao BIAN ; Yajuan NIU
Chinese Mental Health Journal 2025;39(1):87-93
Objective:To examine the validity and reliability of the Chinese version of the Transgender Atti-tudes and Beliefs Scale(TABS)in the general adult population.Methods:A total of 1 656 residents aged≥18 years were recruited by convenient sampling method,and were equally divided into sample 1 and sample 2 accord-ing to age group.The total sample was used for item analysis and internal consistency reliability test.Sample 1 was used for exploratory factor analysis,Sample 2 was used for confirmatory factor analysis,and 60 residents were se-lected for retesting at a 2-week interval.Results:The TABS Chinese version included a total of 26 items,with the content validity index(I-CVI)of each item ranging from 0.83 to 1.00,and the content validity index(S-CVI)of the scale being 0.98.Exploratory factor analysis extracted 3 common factors,namely interpersonal comfort,gender beliefs,and human value,with a cumulative total variance of 57.13%.Confirmatory factor analysis showed that the scale fit was acceptable(x2/df=2.95,RMSEA=0.05,GFI=0.92,AGFI=0.90).The Cronbach α coefficients of the total score of the scale and the scores of the 3 factors were 0.95,0.95,0.88 and 0.86.The retest reliabilities were 0.88,0.78,0.65 and 0.91.Conclusion:The Chinese version of the Transgender Attitudes and Beliefs Scale(TABS)has good validity and reliability in assessing general adults'attitudes toward the transgender community.
3.Levels of serum thymic stromal lymphopoietin and double-negative T lymphocytes in children with bronchial asthma and their clinical significance
Long ZHAO ; Jing WANG ; Cuicui LIU ; Xiaolan SHI
Journal of Chinese Physician 2025;27(7):1019-1023
Objective:To analyze the levels of serum thymic stromal lymphopoietin (TSLP) and double-negative T lymphocytes (DNT) in children with bronchial asthma and their clinical significance.Methods:The clinical data of 147 children with bronchial asthma (study group) diagnosed and treated in Xi′an Children′s Hospital from January to March 2024 were retrospectively analyzed, and the clinical data of 120 children who underwent healthy physical examination in the hospital during the same period (control group) were selected. All subjects underwent serum TSLP and DNT detection. The study group was divided into controlled group (116 cases) and uncontrolled group (31 cases) according to the asthma control level. The levels of TSLP and DNT were compared between the two groups, and the factors affecting the asthma control level in children with bronchial asthma were analyzed. Receiver operating characteristic (ROC) curve was used to analyze the value of TSLP and DNT in predicting the asthma control level in children.Results:The serum TSLP level in the study group was higher than that in the control group, and the DNT level was lower than that in the control group (all P<0.05). The TSLP level, the proportion of severe cases, and the proportion of cases with family history of asthma in the uncontrolled group were higher than those in the controlled group, while the DNT level, age, and forced expiratory volume in the first second/forced vital capacity (FEV 1/FVC) were lower than those in the controlled group (all P<0.05). Multivariate stepwise logistic regression analysis showed that TSLP level ( OR=3.656, 95% CI: 2.091-6.392) and disease severity ( OR=2.561, 95% CI: 1.230-5.330) were independent risk factors affecting asthma control level in children, while DNT level ( OR=0.233, 95% CI: 0.122-0.442) and FEV 1/FVC level ( OR=0.287, 95% CI: 0.127-0.647) were independent protective factors (all P<0.05). ROC curve analysis showed that the sensitivities of TSLP, DNT, and their combination in predicting asthma control level were 74.20%, 71.00%, and 90.30% respectively; the specificities were 75.90%, 73.30%, and 91.40% respectively; the areas under the curve (AUC) were 0.821, 0.805, and 0.923 respectively (all P<0.05). Conclusions:Serum TSLP level is abnormally increased and DNT level is abnormally decreased in children with bronchial asthma. TSLP is an independent risk factor affecting asthma control level in children, and DNT is an independent protective factor. Combined detection of TSLP and DNT can better predict the asthma control status of patients in clinical practice.
4.Comparison of the application of double tract anastomosis and single muscular flap valvuloplasty technique in laparoscopic proximal gastrectomy for digestive tract reconstruction
Hansong FAN ; Qingzhu DING ; Huina WANG ; Zhiyi CHENG ; Chuanjiang HUANG ; Guiyuan LIU ; Xiaojun ZHAO ; Xiaolan YOU
Chinese Journal of Gastrointestinal Surgery 2025;28(11):1291-1301
Objective:To explore the clinical efficacy of double tract reconstruction and single flap valvuloplasty technique in laparoscopic proximal gastrectomy.Methods:A retrospective cohort study was adopted to analyze the clinical data of 65 patients with gastric cancer who underwent radical proximal gastrectomy at Taizhou People's Hospital Affiliated to Nanjing Medical University from July 2019 to April 2024. According to the different reconstruction methods, the patients were divided into the double tract reconstruction group (double tract; n=43) and oblique anastomosis of esophageal-gastric mucosal window with single flap valvuloplasty technique group (single flap n=22). The baseline data, surgical and postoperative recovery indicators, postoperative pathological results, gastroesophageal reflux at postoperative 6 months, and nutritional status at postoperative 1 year were compared between the two groups. Results:Comparisons of operative time, gastrointestinal reconstruction time, number of lymph nodes dissected, postoperative intestinal function recovery time, total protein, plasma albumin, hemoglobin, and lymphocyte count at 1 week postoperatively, prognostic nutritional index (PNI), time to normalization of postoperative white blood cell count and C-reactive protein, length of hospital stay, hospital costs, and incidence of postoperative pulmonary infection or anastomotic leakage between the two groups showed no statistically significant differences (all P>0.05). However, compared with the double tract group, the single muscle flap group had significantly higher intraoperative blood loss ( P<0.001), higher maximum postoperative body temperature ( P=0.004), and a significantly higher proportion of patients with pleural effusion ≥2 cm ( P=0.029).No statistically significant differences were observed between the two groups in terms of tumor length, length of esophageal involvement, Siewert classification, tumor differentiation degree, neural invasion, lymphovascular invasion, number of metastatic lymph nodes, tumor T stage and N stage, or UICC TNM staging for gastric cancer (all P>0.05). Nevertheless, the minimum distance of the lower resection margin in the double tract group was significantly longer than that in the single muscle flap group, with a statistically significant difference between the groups ( P<0.001). At 6 months postoperatively, results from the Quality of Life Questionnaire-Core 30 (QLQ-C30), Quality of Life Questionnaire-Stomach 22 (QLQ-ST022), Reflux Symptom Index scores, Visick grading, and gastroscopy (Los Angeles classification) all indicated that the incidence of reflux esophagitis in the double tract group was significantly lower than that in the single muscle flap group (all P<0.001). Gastrointestinal contrast examination showed no anastomotic stenosis in either group; gastroesophageal reflux occurred in 5 cases (11.6%) in the double tract group and 4 cases (18.2%) in the single muscle flap group, with no statistically significant difference (χ2=0.524, P=0.469). Gastroscopy results revealed that the incidence of reflux esophagitis at 6 months postoperatively was 9.3% (4/43) in the double tract group and 59.1% (13/22) in the single muscle flap group, with a statistically significant difference between the two groups (χ2=18.680, P<0.001).At 1 year postoperatively, the dual-chamber group showed better performance in body mass index(BMI), proportion of a decrease in BMI, plasma albumin, and PNI compared with the single muscle flap group, with statistically significant differences (all P<0.05). There were no statistically significant differences in hemoglobin or lymphocyte count between the two groups (all P>0.05). During 1 year of follow-up, one case of anastomotic recurrence occurred in each group, with no statistically significant difference between the groups ( P=0.624). Conclusions:Both proximal gastrectomy with double-tract anastomosis and esophagogastric mucosal window oblique anastomosis combined with single muscular flap valvuloplasty for digestive tract reconstruction are safe and feasible. However, double-tract anastomosis can better prevent the occurrence of postoperative reflux esophagitis, improve the patient's postoperative nutritional status, and enhance the patient's quality of life.
5.Trajectories and influencing factors of perioperative pain catastrophizing in patients undergoing lumbar internal fixation surgery
Shaojuan TIAN ; Xiaolan ZHAO ; Dakai ZHOU ; Rui SHI ; Zhenjun ZHU
Chinese Journal of Modern Nursing 2025;31(21):2889-2894
Objective:To explore the latent trajectory class of perioperative pain catastrophizing in patients undergoing lumbar internal fixation surgery and analyze the influencing factors of these latent classes.Methods:A total of 180 patients who underwent lumbar internal fixation surgery at Xinxiang Central Hospital from January to December 2023 were selected using convenience sampling. The Pain Catastrophizing Scale (PCS) was used to assess pain catastrophizing at 1 day preoperatively and on postoperative days 3, 7, and 14. Latent Class Growth Modeling (LCGM) was employed to identify trajectory classes of pain catastrophizing, and Logistic regression analysis was used to examine their influencing factors.Results:A total of 177 patients completed the follow-up, with a follow-up rate of 98.33% (177/180) . The overall perioperative PCS score was (30.39±10.86) . PCS scores at 1 day preoperatively and on postoperative days 3, 7, and 14 were (37.63±6.23) , (33.27±6.00) , (28.55±9.02) , and (23.81±9.33) , respectively. The proportions of patients with PCS≥38 at the four times were 42.94% (76/177) , 23.16% (41/177) , 22.60% (40/177) , and 12.43% (22/177) , respectively. LCGM identified three latent trajectory classes of perioperative pain catastrophizing: "high-level declining group" (55.93%, 99/177) , "high-level fluctuating group" (28.81%, 51/177) , and "persistent high-level group" (15.25%, 27/177) . Logistic regression analysis showed that payment method, surgical duration, and preoperative PCS score were significant influencing factors of pain catastrophizing trajectory classes ( P<0.05) . Conclusions:Pain catastrophizing levels in patients undergoing lumbar internal fixation surgery peaked preoperatively. While most patients showed a declining trend postoperatively, a subset exhibited fluctuating or persistently high levels. Payment method, surgical duration, and preoperative pain catastrophizing levels significantly influenced the trajectory of pain catastrophizing, warranting attention from clinical nursing staff.
6.Effects of acupotomy on the expression of fibroblast growth factor family and its receptor in the splenius capitis muscles of rats with cervical spondylosis
Fushui LIU ; Jiaming QIAN ; Ting FANG ; Tumurbaatar KHALIUNAA ; Xiaolan ZHAO ; Jinchao ZHU ; Xiaole WANG
Chinese Journal of Tissue Engineering Research 2025;29(18):3775-3783
BACKGROUND:Acupotomy is an effective method for the treatment of cervical spondylosis with definite clinical efficacy,but its key molecular mechanism is still unclear.OBJECTIVE:To observe the effect of acupotomy intervention on the expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles of rats with cervical spondylosis,and to study the therapeutic mechanism of acupotomy in cervical spondylosis.METHODS:The Genomics Expression Omnibus Database was searched to obtain the microarray dataset GSE153761,which was compatible with the study,and a bioinformatics approach was used for the initial screening of targets,followed by animal experiments.Twenty-four 6-month-old SPF grade Sprague-Dawley rats were randomly divided into four groups.The model of cervical spondylosis was established by unbalanced dynamic and static forces in the model and acupotomy groups.The muscles and ligaments were not cut in the sham operation group.After successful modeling,acupotomy intervention was performed in the acupotomy group,once a week,3 times in total.Normal rats were selected as controls.The posteroanterior and lateral X-rays of the cervical spine were taken for modeling verification;the open-field tests were performed in all rats to observe behavioral changes;the pathological structure of the splenius capitis muscles was observed by hematoxylin-eosin staining;the mRNA and protein expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles was detected by fluorescent quantitative PCR and immunohistochemical method,respectively.RESULTS AND CONCLUSION:Bioinformatics results indicated that fibroblast growth factor family/kinase insert domain protein receptor is an important signal axis for activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.After modeling,the intervertebral space of the rats was narrowed,and the anterior and posterior borders of the vertebral body and the articular process were hyperosteogenous.In the open-field tests,the total distance and average speed in the model group were decreased after modeling(P<0.05),while the total rest time in the model group was increased(P<0.05).After treatment,the total distance and average speed in the acupotomy group were greater than those in the model group(P<0.05),while the total rest time in the acupotomy group was shorter than that in the model group(P<0.05).The pathological changes of the splenius capitis muscles indicated damage to the cervical muscle,and acupotomy improved cervical muscle strain.Compared with the normal group,The mRNA and protein expressions of fibroblast growth factor 7,fibroblast growth factor 9,fibroblast growth factor 10,fibroblast growth factor 18,and kinase insert domain protein receptor in the splenius capitis muscles were increased in the model group compared with the normal group(P<0.05).In contrast,acupotomy treatment could downregulate the above indicators(P<0.05).Thus,acupotomy may repair cervical muscle strain by regulating the expression of fibroblast growth factor 7,fibroblast growth factor 9,fibroblast growth factor 10,fibroblast growth factor 18,and kinase insert domain protein receptor,thereby improving intervertebral disc degeneration,which may be the key target for acupotomy treatment of cervical spondylosis.
7.Trends of Incidence and Age at Onset of Leukemia in Jiangsu Cancer Registration Areas from 2009 to 2019
Haiyan LU ; Xinxin DONG ; Xingxing ZHU ; Dekun ZHANG ; Yuxue YANG ; Xiaolan ZHAO ; Renqiang HAN ; Jinyi ZHOU ; Ran TAO ; Weigang MIAO ; Pengfei LUO
China Cancer 2025;34(2):125-131
[Purpose]To analyze the trends of incidence and age at onset of leukemia in Jiangsu cancer registration areas from 2009 to 2019.[Methods]The continuous monitoring data of leukemia from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province.All datasets were checked and evaluated based on data quality control criteria and were included in the analysis.Crude incidence rate(CIR),age-standardized incidence rate by Chinese standard population(ASIRC),the average annual percentage change(AAPC),the standardized average age at onset,the changes in the age structure of incidence and the changes in the birth cohort by year were calculated.[Results]The incidence rate of leukemia significantly increased from 5.22/105 in 2009 to 7.88/105 in 2019,with a significant upward trend(for CIR,AAPC=4.95%,95%CI:3.82%~6.09%;for ASIRC,AAPC=2.97%,95%CI:1.52%~4.43%).The incidence rates were in-creased in all age groups and increased with the birth cohort by years.There was a tendency of backward shift for the age composition of the population,with the increasing of composition for those over 60 years old.The mean age at onset increased from 48.62 years old in 2009 to 57.96 years old in 2019,with a backward shift in the mean age(β=0.773,P<0.001),and the mean age at onset increased with the year only in rural areas after standardization(β=0.428,P=0.017).[Conclusion]Leukemia incidence rate in Jiangsu Province increased from 2009 to 2019,and the age at onset has shifted backwards.It's important to strengthen the early prevention and control of leukemia.
8.Clinical study on transcutaneous electrical acupoint stimulation combined with skin sympathetic response to evaluate autonomic nerve preservation after laparoscopic radical gastrectomy
Qingzhu DING ; Jin GAO ; Huina WANG ; Zhiyi CHENG ; Chuanjiang HUANG ; Guiyuan LIU ; Xiaojun ZHAO ; Xing CHE ; Xiaolan YOU
Chinese Journal of Gastrointestinal Surgery 2025;28(2):178-184
Objective:This study aimed to explore the utility of transcutaneous electrical acupoint stimulation (TEAS) combined with skin sympathetic response (SSR) in assessing the effectiveness of perigastric autonomic nerve preservation during radical gastrectomy.Methods:A retrospective cohort analysis was conducted involving 221 patients who underwent laparoscopic radical gastrectomy at the Department of Gastric Surgery, Taizhou People's Hospital, affiliated with Nanjing Medical University, between June 2022 and September 2024. The cohort comprised 109 patients who underwent laparoscopic radical total gastrectomy without autonomic nerve preservation (total gastrectomy without nerve preservation group). Additionally, 112 patients underwent laparoscopic radical distal gastrectomy, including 34 patients who received autonomic nerve preservation (nerve preservation group) and 78 patients who did not (without nerve preservation group). TEAS was administered at the Zusanli and Tianshu acupoints one day before and one day after surgery, during which SSR latency and voltage amplitudes in the upper and lower extremities were recorded and compared across groups. Differences in SSR latency and voltage amplitude between the nerve preservation and non-nerve preservation groups of the distal gastrectomy cohort were also analyzed. Further, TEAS was applied at the same acupoints for 15 minutes on the 1st, 2nd, and 3rd postoperative days, and changes in intestinal sounds and intestinal functional recovery time were monitored. Surgical parameters, including operative duration, intraoperative blood loss, and harvested lymph node, were documented. Postoperative inflammatory indicators, including interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), and the incidence of anastomotic leakage, were evaluated. At three months postoperatively, gastroscopy was performed to assess residual gastric food and bile reflux. Additionally, the prognostic nutritional index (PNI) was evaluated across all patient groups.Results:Following total gastrectomy, TEAS of Zusanli combined with arms' SSR revealed a latency of (23 59.71±410.55) ms and a voltage amplitude of (0.43±1.67) mV; for the legs, latency was (2 596.88±369.01) ms and voltage amplitude was (0.25±0.08) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (2 746.47±224.37) ms and a voltage amplitude of (0.31±0.14) mV; for the legs, latency was (2 891.90±193.61) ms and voltage amplitude was (0.19±0.72) mV. Postoperative latency was significantly prolonged, and voltage amplitude was markedly reduced (all P < 0.01). In the distal gastrectomy with nerve preservation group, TEAS of Zusanli combined with arms' SSR showed a latency of (1 668.04±261.91) ms and a voltage amplitude of (0.78±0.26) mV; for the legs, latency was (1 568.86±220.09) ms and voltage amplitude was (0.61±0.24) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (1 519.36±206.99) ms and a voltage amplitude of (0.66±0.34) mV; for the legs, latency was (2 004.80±508.53) ms and voltage amplitude was (0.55±0.28) mV. In the distal gastrectomy without nerve preservation group, TEAS of Zusanli combined with arms' SSR revealed a latency of (2 385.95±710.27) ms and a voltage amplitude of (0.23±0.11) mV; for the legs, latency was (2 506.81±779.37) ms and voltage amplitude was (0.26±1.29) mV. TEAS of Tianshu combined with arms' SSR indicated a latency of (2 697.78±385.55) ms and a voltage amplitude of (0.21±0.14) mV; for the legs, latency was (2 949.14±506.61) ms and voltage amplitude was (0.17±0.11) mV. The group without nerve preservation exhibited significantly prolonged latencies and reduced voltage amplitudes (all P<0.01). No statistically significant differences were observed between the groups in operative time, intraoperative bleeding, the number of dissected lymph nodes, inflammatory indicators (IL-6, CRP, PCT) at 3 days postoperatively, or anastomotic leakage rates (all P>0.05). In the group without nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.36±0.58), (1.04±0.97), and (1.74±1.10) times/min, respectively, with bowel function recovery time of (62.24±9.91) hours. The PNI at 3 months postoperatively was (37.42±3.01). Incidences of food residue in the residual stomach and bile reflux were 21.79% (17/78) and 29.49% (23/78), respectively. In the group with nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.76±0.82), (2.03±1.34), and (3.71±1.27) times/min, respectively, with bowel function recovery time of (44.94±8.05) hours. The PNI at 3 months postoperatively was (41.34±3.40). Incidences of food residue and bile reflux were 5.88% (2/34) and 11.76% (4/34), respectively. Statistically significant differences were observed between the groups (all P < 0.05). Conclusion:TEAS of Zusanli and Tianshu combined with SSR provides an objective measure for assessing the preservation of perigastric autonomic nerves during radical gastrectomy.
9.Isorhamnetin alleviates pathological damage in influenza A virus strain PR8-induced pneumonia by activating the Nrf2/HO-1 pathway and suppressing apoptosis
Yingli XU ; Shuran LI ; Ronghua ZHAO ; Lei BAO ; Zihan GENG ; Qiyue SUN ; Bo PANG ; Xiaolan CUI ; Shanshan GUO ; Jing SUN
Science of Traditional Chinese Medicine 2025;3(1):28-39
Background: Influenza A viruses (IAVs) are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications. Isorhamnetin, an abundant natural flavonoid in fruits and medicinal plants, has recently been shown to have strong antioxidative, anti-inflammatory, and antiviral effects. Objective: This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments. Materials and methods: In the present study, the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay, cell counting kit-8 assay, real-time polymerase chain reaction, and immunofluorescence assay in vitro. Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo. Thereafter, the related protein or gene levels of factors in the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were determined by Western blot and immunofluorescence staining. Results: Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells, counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3. The in vivo experiment results showed that isorhamnetin (20 and 40 mg/kg) caused a significant decrease in the pulmonary index, ameliorated pathological damage in the lung tissue, decreased viral load and NA activity, and reduced cytokines and nuclear factors. Furthermore, isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2–associated X protein (Bax) imbalance induced by PR8, suppress activation of the MAPK pathway, and upregulate the expression of Nrf2 and HO-1. Conclusions: Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way. This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.
10.Isorhamnetin alleviates pathological damage in influenza A virus strain PR8-induced pneumonia by activating the Nrf2/HO-1 pathway and suppressing apoptosis
Yingli XU ; Shuran LI ; Ronghua ZHAO ; Lei BAO ; Zihan GENG ; Qiyue SUN ; Bo PANG ; Xiaolan CUI ; Shanshan GUO ; Jing SUN
Science of Traditional Chinese Medicine 2025;3(1):28-39
Background: Influenza A viruses (IAVs) are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications. Isorhamnetin, an abundant natural flavonoid in fruits and medicinal plants, has recently been shown to have strong antioxidative, anti-inflammatory, and antiviral effects. Objective: This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments. Materials and methods: In the present study, the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay, cell counting kit-8 assay, real-time polymerase chain reaction, and immunofluorescence assay in vitro. Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo. Thereafter, the related protein or gene levels of factors in the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were determined by Western blot and immunofluorescence staining. Results: Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells, counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3. The in vivo experiment results showed that isorhamnetin (20 and 40 mg/kg) caused a significant decrease in the pulmonary index, ameliorated pathological damage in the lung tissue, decreased viral load and NA activity, and reduced cytokines and nuclear factors. Furthermore, isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2–associated X protein (Bax) imbalance induced by PR8, suppress activation of the MAPK pathway, and upregulate the expression of Nrf2 and HO-1. Conclusions: Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way. This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.

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