Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

Objective:To investigate the impact of the interval between neoadjuvant immunotherapy combined with chemotherapy(nICT) and surgery on pathological outcomes and prognosis in patients.Methods:This is a retrospective cohort study. A total of 115 patients with locally advanced esophageal squamous cell carcinoma who underwent nICT followed by sequential surgery at Department of Thoracic Surgery, Peking University People′s Hospital or Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2024 were included. Among them, 99 were male and 16 were female, with an age of ( M(IQR)) 65 (11) years (range:45 to 81 years). All patients received 2 to 6 cycles of paclitaxel plus platinum-based doublet chemotherapy combined with PD-1 immune checkpoint inhibitors. The resectability of tumors was assessed based on CT scans of the chest and abdomen, and surgical approaches included Sweet surgery, Mckeown surgery, and Ivor-Lewis surgery. Patients were divided into a short-interval group (4 to <6 weeks) and a long-interval group (6 to 12 weeks) based on the interval between neoadjuvant immunochemotherapy and surgery. General patient data, surgical details, pathological response, and prognosis were collected and analyzed. Data comparisons were performed using independent sample t-test, Mann-Whitney U test, χ 2 test, or Fisher′s exact test. Multivariate logistic regression analysis was used to identify independent factors influencing pathological complete response (pCR). Survival analysis was conducted using the Kaplan-Meier method and Log-rank test. Results:There were no significant differences in baseline characteristics, neoadjuvant treatment details, surgical outcomes, or postoperative complications between the long-interval group and the short-interval group (all P>0.05). Multivariate Logistic regression analysis revealed that, among clinical factors, interval between neoadjuvant immunochemotherapy and surgery was significantly associated with pCR (long-interval group vs. short-interval group: OR=4.14, 95% CI:1.63 to 10.50, P=0.003). The pCR rate was higher in the long-interval group (43.6% vs. 17.1%, χ2=6.48, P=0.011). Survival analysis showed no significant differences in overall survival ( P=0.094) or disease-free survival ( P=0.840) between the two groups. Conclusion:Appropriately extending the surgical interval after neoadjuvant immunochemotherapy maybe lead to a higher pCR rate, without increasing surgical difficulty or damaging prognosis.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

Objective:To investigate the impact of the interval between neoadjuvant immunotherapy combined with chemotherapy(nICT) and surgery on pathological outcomes and prognosis in patients.Methods:This is a retrospective cohort study. A total of 115 patients with locally advanced esophageal squamous cell carcinoma who underwent nICT followed by sequential surgery at Department of Thoracic Surgery, Peking University People′s Hospital or Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2024 were included. Among them, 99 were male and 16 were female, with an age of ( M(IQR)) 65 (11) years (range:45 to 81 years). All patients received 2 to 6 cycles of paclitaxel plus platinum-based doublet chemotherapy combined with PD-1 immune checkpoint inhibitors. The resectability of tumors was assessed based on CT scans of the chest and abdomen, and surgical approaches included Sweet surgery, Mckeown surgery, and Ivor-Lewis surgery. Patients were divided into a short-interval group (4 to <6 weeks) and a long-interval group (6 to 12 weeks) based on the interval between neoadjuvant immunochemotherapy and surgery. General patient data, surgical details, pathological response, and prognosis were collected and analyzed. Data comparisons were performed using independent sample t-test, Mann-Whitney U test, χ 2 test, or Fisher′s exact test. Multivariate logistic regression analysis was used to identify independent factors influencing pathological complete response (pCR). Survival analysis was conducted using the Kaplan-Meier method and Log-rank test. Results:There were no significant differences in baseline characteristics, neoadjuvant treatment details, surgical outcomes, or postoperative complications between the long-interval group and the short-interval group (all P>0.05). Multivariate Logistic regression analysis revealed that, among clinical factors, interval between neoadjuvant immunochemotherapy and surgery was significantly associated with pCR (long-interval group vs. short-interval group: OR=4.14, 95% CI:1.63 to 10.50, P=0.003). The pCR rate was higher in the long-interval group (43.6% vs. 17.1%, χ2=6.48, P=0.011). Survival analysis showed no significant differences in overall survival ( P=0.094) or disease-free survival ( P=0.840) between the two groups. Conclusion:Appropriately extending the surgical interval after neoadjuvant immunochemotherapy maybe lead to a higher pCR rate, without increasing surgical difficulty or damaging prognosis.

BackgroundPrevious studies have found that patients with generalized anxiety disorder （GAD） have impaired performance in executive function， and group cognitive behavioral therapy （CBT） has been shown to be effective in alleviating negative affect in patients with GAD， while its efficacy on executive function remains unclear. ObjectiveTo explore the efficacy of group CBT on anxiety symptom and executive function in GAD patients， so as to provide references for the rehabilitation program for GAD. MethodsA total of 80 consecutive patients with GAD who were hospitalized in Sleep and Psychosomatic Medical Center of Shiyan Taihe Hospital from March 2021 to August 2022 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for GAD were enrolled， and they were assigned into study group （n=40） and control group （n=40） using random number table methods. All patients were subjected to routine medication treatment and regular health education， based on this， study group received group CBT once a week （6 weeks， 60 to 90 minutes per session）. At the enrollment and after 6 weeks of treatment， patients were assessed using Hamilton Anxiety Scale （HAMA） and Frontal Assessment Battery （FAB）. ResultsANOVA with repeated measures on HAMA score revealed a significant time effect （F=1 870.320， P<0.01）， no significant group effect and no significant time×group interaction effect （F=1.254， 0.293， P>0.05）. Significant time effect， group effect and time×group interaction effect were reported on FAB scores （F=311.190， 4.399， 7.021， P<0.05 or 0.01）. Further analysis indicated that FAB scores of both groups after treatment were higher than those at baseline （t=200.569， 115.401， P<0.01）.And the FAB score of study group was higher than that of control group after treatment （t=-3.211， P<0.01）. ConclusionGroup CBT combined with medication treatment for GAD may alleviate the anxiety symptoms and improve executive function in GAD patients. ［Funded by Shiyan Science and Technology Bureau Pilot Scientific Research Project （number， 21Y21）］

Objective:To investigate the early clinical outcomes of a minimally invasive anterolateral approach (Orthopadische chirurgie munchen, OCM) versus a conventional (posterolateral approach, PLA) hemiarthroplasty in the treatment of senior femoral neck fractures.Methods:A retrospective analysis was performed on 90 elderly patients with femoral neck fractures who received anterolateral and posterolateral approaches for hemiarthroplasty in the Second Affiliated Hospital of Soochow University from December 2019 to June 2021 and were followed up. In the OCM group, there were 45 cases, including 18 males and 27 females, aged 83.33±5.29 years (range, 76-96 years); In the PLA group, there were 45 cases, including 13 males and 32 females, aged 81.87±5.00 years (range, 75-94 years). Postoperative, surgical indices, perioperative bleeding, and soft tissue injury were assessed; pain was assessed using the visual analogue scale (VAS), and hip function was evaluated using the Harris score and the University of California at Los Angeles (UCLA) score.Results:The incision length, postoperative hospital stay, hemoglobin reduction, and occult blood loss were lower in the OCM group than in the PLA group ( P<0.05), but there was no significant difference in intraoperative bleeding and postoperative transfusion rate ( P>0.05). Serum creatine kinase and C-reactive protein levels (232.98±83.70 IU/L and 81.67±48.85 mg/L) were lower in the OCM group than in the PLA group (296.93±124.58 IU/L and 104.79±36.75 mg/L) 1 day after surgery, and the differences were statistically significant ( t=2.86, P=0.005; t=2.54, P=0.013). Postoperative pain was significantly improved in all patients, and VAS scores were lower in the OCM group than in the PLA group at 12 h, 24 h, and 48 h postoperatively ( P<0.05). The time to get out of bed after surgery was 20.73±4.99 h in the OCM group compared with 41.69±13.58 h in the PLA group, with a statistically significant difference ( t=9.71, P<0.001). Harris scores (63.31±6.21 and 75.76±4.91) and UCLA scores (1.84±0.42 and 3.69±0.76) were higher in the OCM group on the day of discharge and at 1 month postoperatively than in the PLA group (52.69±10.01 and 71.33±3.66); (1.62±0.54 and 3.16±0.80) points, all with statistically significant differences ( P<0.05). However, the differences in Harris score and UCLA score between the two groups at 6 months postoperatively were not statistically significant ( P>0.05). There were two cases of intermuscular vein thrombosis in the OCM group, with a complication rate of 4% (2/45), and one case of dislocation in the PLA group, with a complication rate of 2% (1/45), there was no significant difference between the two groups ( P=1.000). Conclusion:The minimally invasive anterolateral approach is a more ideal procedure for elderly patients with femoral neck fractures undergoing hemiarthroplasty. It has the advantages of a short incision, small soft tissue damage, low occult blood loss, early removal from bed, a short postoperative hospital stay, an improvement in pain, and a good early recovery of hip function.

OBJECTIVE: This study aimed to reveal the insomnia burden and relevant influencing factors among informal caregivers (ICs) of hospitalized patients with lung cancer. METHODS: A cross-sectional study on ICs of hospitalized patients with lung cancer was conducted from December 31, 2020 to December 31, 2021. ICs' burden was assessed using the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Linear and logistic regression models were used to identify the influencing factors. RESULTS: Among 289 ICs of hospitalized patients with lung cancer, 83 (28.72%), 53 (18.34%), and 14 (4.84%) ICs experienced mild, moderate, and severe insomnia, respectively. The scores concerning self-esteem, lack of family support, financial problems, disturbed schedule, and health problems were 4.32 ± 0.53, 2.24 ± 0.79, 2.84 ± 1.14, 3.63 ± 0.77, and 2.44 ± 0.95, respectively. ICs with higher Activities of Daily Living Scale (ADLS) scores were associated with a lower risk of insomnia, with an odd ratio ( OR) and 95% confidence interval ( CI) of 0.940 (0.898-0.983). Among the ICs, female gender ( OR = 2.597), alcohol consumption ( OR = 3.745), underlying medical conditions ( OR = 11.765), long-term caregiving experience ( OR = 37.037), and higher monthly expenses ( OR = 5.714) were associated with a high risk of insomnia. CONCLUSION Of the hospitalized patients with lung cancer, 51.9% experienced insomnia. Patients' ADL, ICs gender, alcohol consumption, underlying medical conditions, caregiving duration, and monthly expenses were influencing factors. Therefore, prompt screening and early intervention for ICs of patients with lung cancer is necessary.
Humans ; Female ; Caregivers ; Activities of Daily Living ; Cross-Sectional Studies ; Sleep Initiation and Maintenance Disorders/epidemiology* ; Lung Neoplasms/epidemiology*

ObjectiveTo investigate the effect of Qi-invigorating and blood-activating therapy on the miR216b/Beclin1 pathway in mice with atrophic precancerous lesions of gastric cancer （PLGC） and analyze its mechanism in autophagy of PLGC. MethodSeventy-five healthy male SPF KM mice were randomly divided into a blank group and a model group. Mice in the model group were given 1-methyl-3-nitroso-1-nitrosoguanidine （MNNG） solution （150 mg·L^-1） for free drinking and gavage and ranitidine solution （0.03 g·kg^-1） daily for 12 weeks. According to the random control table， mice were divided into a model group， a Qi-invigorating group （3.5 g·kg^-1 of Astragali Radix）， a blood-activating group （0.7 g·kg^-1 of Notoginseng Radix et Rhizoma powder）， a Qi-invigorating and blood-activating group （3.5 g·kg^-1 of Astragali Radix + 0.7 g·kg^-1 of Notoginseng Radix et Rhizoma powder）， and a folic acid group （2 mg·kg^-1）. The corresponding drugs were given to mice in each group for 8 weeks and then the tissues were collected. Hematoxylin-eosin （HE） staining was carried out to observe the changes in gastric mucosa. Western blot was used to detect the protein expression of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， and Beclin1. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Beclin1 and miR-216b. ResultPathological observation showed that as compared with the blank group， the intrinsic glands of gastric mucosa decreased with atrophy and intestinal metaplasia in the model group， which were improved in all treatment groups， and the improvement of the Qi-invigorating and blood-activating group was the most obvious. As compared with the blank group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of the model group was significantly decreased （P<0.05）. As compared with the model group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of each treatment group was increased （P<0.05， P<0.01）. The increase was most obvious in the Qi-invigorating and blood-activating group. As compared with the blank group， the mRNA expression of Beclin1 in the model group was decreased （P<0.05）， and that of miR216b was increased （P<0.05）. As compared with the model group， the mRNA expression of Beclin1 was increased and that of miR216b was decreased in each treatment group （P<0.05）， and the changes were the most obvious in the Qi-invigorating and blood-activating group. ConclusionThe mechanism of the Qi-invigorating and blood-activating therapy， represented by Astragali Radix and Notoginseng Radix et Rhizoma， in treating PLGC may be through inhibiting the expression of miR216b and activating Beclin1， thus promoting autophagy and repairing gastric mucosa.

This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
Animals ; Humans ; Male ; Mice ; Rats ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Phosphodiesterase 5 Inhibitors ; Plasminogen Activator Inhibitor 1