1.Effect of Dingchuan Granule (定喘颗粒) on Lung Tissue Oxidative Stress and Nrf2/Keap1/HO-1/NQO1 Pathway in Respiratory Syncytial Virus Pneumonia Model Rats
Lai ZHANG ; Xiuying ZHANG ; Chenhao WEI ; Shiyao ZHANG ; Zhaoyang LI ; Rui WANG ; Hangyu ZHAO
Journal of Traditional Chinese Medicine 2025;66(15):1588-1596
ObjectiveTo explore the potential mechanism of Dingchuan Granule (定喘颗粒, DG) in the treatment of respiratory syncytial virus (RSV) pneumonia. MethodsA total of 60 male Sprague Dawley (SD) rats were randomly divided into control group, model group, ribavirin group, DG low-dose group, DG middle-dose group, and DG high-dose group, with 10 rats in each group. Except for the control group, rats were administrated with RSV via intranasal drip. After model establishment, the DG low-, middle-, and high-dose groups were administrated via oral gavage with DG at 3.47, 6.93, and 13.86 g/(kg·d) respectively, while the ribavirin group was administrated via oral gavage with ribavirin at 15.75 mg/(kg·d). The drug was given once daily for one week. The rats in the control group and the model group were not given any drug, only subjected to the grasping action. Twenty-four hours after the last administration, the pathological changes of lung tissues were observed and scored using HE staining. The levels of serum inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), were detected by colorimetry. The protein levels of nuclear factor (erythroid derived 2)-like 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in lung tissues were measured by Western Blot. The RSV load as well as the gene expression levels of Nrf2, Keap1, HO-1, and NQO1 in lung tissues were determined by qRT-PCR. The level of reactive oxygen species (ROS) in rat lung tissues was detected using chemiluminescence. The levels of glutathione (GSH) and malondialdehyde (MDA) in rat lung tissues were measured by a microassay. ResultsCompared with the control group, other groups had significant increases in pathological score of lung tissue, RSV load, levels of ROS, MDA, serum TNF-α, IL-1β, and IL-6; decrease in GSH level, increases in expression level of Keap1 protein and its mRNA in lung tissue, and significant decrease in levels of Nrf2, HO-1, expression level of NQO1 protein and its mRNA (P<0.05). Compared with the model group, all the above-mentioned indicators in the DG low-, middle-, and high-dose groups and the ribavirin group were improved to varying degree (P<0.05). The levels of serum TNF-α, IL-1β, and IL-6 in rats of DG dose groups showed a dose-dependent pattern, the DG high-dose group exhibiting the best effect (P<0.05). The DG high-dose group was superior to the DG low- and middle-dose groups in reducing the levels of ROS and MDA, and increasing the level of GSH in lung tissues (P<0.05). The DG high-dose group and the ribavirin group had better effect than the DG middle-dose group in reducing the RSV load (P<0.05). The DG high-dose group was superior to the ribavirin group in improving the protein levels of Nrf2, Keap1, HO-1, and NQO1 (P<0.05). ConclusionDG could inhibit oxidative stress by regulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway to improve pulmonary inflammation and treat RSV pneumonia, with the DG high-dose group showing the best effect.
2.Effect of Tongxinluo Capsules on Use of Anti-ischemic Drugs in Patients with Chronic Coronary Syndrome of Qi Deficiency and Blood Stasis: A Multicenter, Prospective Cohort Study
Chenhao ZHANG ; Jia WANG ; Yiying LIU ; Xiaohe YANG ; Xuesen WANG ; Meili GAO ; Yu DONG ; Xiaotao LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):149-156
ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome (CCS) of Qi deficiency and blood stasis. MethodA multicenter,prospective cohort study was conducted,with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group (combination of traditional Chinese and western medicine) and a non-exposed group (western medicine alone),and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3,6,12 months. ResultA total of 186 patients were enrolled,with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up,the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group (P<0.01),and this difference remained statistically significant at 6 months (P<0.05) but was no longer significant at 12 months. At the 3- and 6-month follow-ups,there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However,at the 12-month follow-up,the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group (P<0.01). At the 3-month follow-up,both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline (P<0.05),with a more pronounced reduction in the exposed group (P<0.05). At the 6-month follow-up,the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline (P<0.05),while no significant changes were observed in the non-exposed group. At the 12-month follow-up,the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant (P<0.05),while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.
3.Minimally invasive aortic valve replacement with Perceval sutureless aortic bioprosthesis through upper ministernotomy or right anterior thoracotomy
Peng YANG ; Yi XIE ; Chenhao WANG ; Yu LIU ; Qianlei LANG ; Wenfan LI ; Jia HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(03):439-445
Objective To evaluate the clinical effect of minimally invasive aortic valve replacement with Perceval sutureless aortic bioprosthesis in upper ministernotomy or right anterior thoracotomy. Methods From March to November 2022, the patients with simple aortic valve disease were enrolled in the Department of Cardiovascular Surgery of West China Hospital, Sichuan University. After preoperative evaluation, Perceval sutureless bioprosthesis was successfully used to perform aortic valve replacement through the upper ministernotomy or right anterior thoracotomy. The perioperative clinical data and ultrasonic measurement data of all patients were recorded. Results A total of 5 patients with simple aortic valve disease were included, including 3 females and 2 males, with a mean age of 71.2 years. Perceval sutureless bioprosthesis was successfully implanted in 5 patients, with a success rate of 100%. There were 3 patients receiving upper ministernotomy and 2 patients receiving right anterior thoracotomy. Two patients underwent ascending aortic plasty at the same time. The mean cardiopulmonary bypass time was 61.0 min, and aortic cross-clamping time was 32.2 min. All patients were discharged successfully without perivalvular leakage, atrioventricular block or stroke. Conclusion The implantation method of Perceval sutureless bioprosthesis is simple, which can effectively reduce the perioperative risk by shortening the overall operation time, cardiopulmonary bypass time and aortic cross-clamping time. At the same time, its clinical application has promoted the development and popularization of minimally invasive aortic valve replacement, which together with Perceval sutureless bioprosthesis effectively combinates surgical effect and minimally invasive treatment, and has a good clinical application prospect because of its reliable safety and effectiveness.
4.Two-stage retrograde hybrid repair in the surgical treatment of acute aortic dissection complicated with distal malperfusion syndrome
Peng YANG ; Yi XIE ; Yu LIU ; Yu ZHANG ; Qianlei LANG ; Wenfan LI ; Chenhao WANG ; Zhenghua XIAO ; Jia HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(04):585-593
Objective To evaluate the clinical efficacy of two-stage retrograde hybrid repair for acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome. Methods From May 2019 to December 2022, the patients presented with acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome treated in the Department of Cardiovascular Surgery of West China Hospital, Sichuan University were enrolled. After preoperative evaluation, all patients underwent priority emergency interventional surgery to improve distal malperfusion, and then underwent two-stage hybrid surgery to repair proximal aortic lesions. The perioperative clinical and imaging data were retrospectively analyzed. Results Five patients were collected, including 4 males and 1 female, with a median age of 58 years. The main manifestations were lower limb ischemia and renal insufficiency in 3 patients, and poor intestinal perfusion in 2 patients. All patients were given priority to interventional surgery to implant graft stents or bare stents and necessary branch artery intervention, and then successfully performed two-stage hybrid surgery, including type Ⅰhybrid surgery for 2 patients, type Ⅱ hybrid surgery for 1 patient and type Ⅲ hybrid surgery for the other 2 patients, with a success rate of 100.0%. All patients were discharged successfully, and the function of the organs with poor perfusion returned to normal. Only 1 patient recovered to grade 4 muscle strength of the diseased lower limbs upon discharge. No adverse events such as amputation, exploratory laparotomy and intestinal resection or long-term hemodialysis occurred. Conclusion The application of two-stage retrograde hybrid repair in the surgical treatment of acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome is safe and effective, and is helpful to improve the perioperative survival rate, and clinical outcomes of such patients.
5.Cronkhite-Canada Syndrome Combined with Asymptomatic Novel Coronavirus Infection: A Case Report
Ning ZHANG ; Chenhao YANG ; Liangrui ZHOU ; Xiaohong SUN ; Xiaohong LIU ; Lin KANG ; Ji LI ; Hailong LI
Medical Journal of Peking Union Medical College Hospital 2024;15(2):406-412
This article presents a case study of a patient who had Cronkhite-Canada syndrome in combination with an asymptomatic novel coronavirus infection. The patient exhibited clinical symptoms of loss of appetite, hair and nail loss, and skin pigmentation. Digestive endoscopy revealed widespread and varying-sized polypoid changes in the mucosa of the stomach, duodenum, and colon. During the course of the illness, the patient tested positive for novel coronavirus nucleic acid. Treatment with moderate doses of prednisone resulted in the patient's hair regrowth and decreased skin hypopigmentation. The article provides a summary of the patient's diagnosis and treatment and a review of relevant literature, with the aim of enhancing clinicians' understanding of the disease.
6.3dMD photogrammetric system study of thoracic deformation after multi-rib autologous rib cartilage transplantation for auricle reconstruction
Shuang WANG ; Leren HE ; Hengyuan MA ; Binghang LI ; Dongwen JIANG ; Chenhao MA
Chinese Journal of Plastic Surgery 2024;40(10):1080-1085
Objective:To analyze the characteristics of postoperative thoracic deformation in patients who underwent multi-rib autologous rib cartilage transplantation auricle reconstruction based on 3dMD imaging system.Methods:A retrospective study was conducted using 3dMD data of the thorax from patients who underwent auricle reconstruction surgery using multiple autologous costal cartilages at the First Department of Ear Reconstruction of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from July to September 2019. The normal-side chest wall image was superimposed on the rib-harvested side chest wall for automatic registration and alignment, with distance numerical data presented in a Cartesian heat map through color mapping technology. By observing the areas where the rib-harvested side thorax had obvious deformation, the distance difference of the concave and convex peaks on the sagittal diameter was measured to judge the degree of thoracic deformation in children (≤10 mm as none; >10-20 mm as mild; >20-30 mm as moderate; >30 mm as severe).Results:A total of 42 children were included, with 27 males and 15 females, aged from 7 to 12 years old. The Cartesian heat map of thoracic deformation showed that the obvious concave area of the chest wall was located at the junction of the middle and inner one-third of the clavicle and the 7th rib, and the obvious convex area was located in the area from the nipple to the 5th rib. The measurement range of the protrusion peak in the upper chest nipple area was from -7.638 9 to -14.288 4 mm; the measurement range of the depression peak in the rib arch area was from 7.238 7 to 14.653 2 mm. The range of the distance difference between the concave and convex peaks was from 14.877 6 to 28.941 6 mm.The degree and incidence of thoracic deformation in children: mild in 5 cases; moderate in 37 cases.Conclusion:Based on the analysis with 3dMD photogrammetry, the overall characteristics of chest wall deformation in patients who underwent ear reconstruction with autologous rib cartilage grafts were the coexistence of protrusion in the upper chest nipple area and depression in the area where the rib cartilage was harvested, with changes occurring on the sagittal diameter.
7.3dMD photogrammetric system study of thoracic deformation after multi-rib autologous rib cartilage transplantation for auricle reconstruction
Shuang WANG ; Leren HE ; Hengyuan MA ; Binghang LI ; Dongwen JIANG ; Chenhao MA
Chinese Journal of Plastic Surgery 2024;40(10):1080-1085
Objective:To analyze the characteristics of postoperative thoracic deformation in patients who underwent multi-rib autologous rib cartilage transplantation auricle reconstruction based on 3dMD imaging system.Methods:A retrospective study was conducted using 3dMD data of the thorax from patients who underwent auricle reconstruction surgery using multiple autologous costal cartilages at the First Department of Ear Reconstruction of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from July to September 2019. The normal-side chest wall image was superimposed on the rib-harvested side chest wall for automatic registration and alignment, with distance numerical data presented in a Cartesian heat map through color mapping technology. By observing the areas where the rib-harvested side thorax had obvious deformation, the distance difference of the concave and convex peaks on the sagittal diameter was measured to judge the degree of thoracic deformation in children (≤10 mm as none; >10-20 mm as mild; >20-30 mm as moderate; >30 mm as severe).Results:A total of 42 children were included, with 27 males and 15 females, aged from 7 to 12 years old. The Cartesian heat map of thoracic deformation showed that the obvious concave area of the chest wall was located at the junction of the middle and inner one-third of the clavicle and the 7th rib, and the obvious convex area was located in the area from the nipple to the 5th rib. The measurement range of the protrusion peak in the upper chest nipple area was from -7.638 9 to -14.288 4 mm; the measurement range of the depression peak in the rib arch area was from 7.238 7 to 14.653 2 mm. The range of the distance difference between the concave and convex peaks was from 14.877 6 to 28.941 6 mm.The degree and incidence of thoracic deformation in children: mild in 5 cases; moderate in 37 cases.Conclusion:Based on the analysis with 3dMD photogrammetry, the overall characteristics of chest wall deformation in patients who underwent ear reconstruction with autologous rib cartilage grafts were the coexistence of protrusion in the upper chest nipple area and depression in the area where the rib cartilage was harvested, with changes occurring on the sagittal diameter.
8.Expression of GLIS3 protein in triple negative breast cancer and its influence on prognosis of patients
Chenhao LI ; Yueping LIU ; Chunxiao LI ; Guozhong CUI ; Xuchen HUANG ; Yi ZHANG ; Guoyu ZHANG ; Cuizhi GENG
Journal of Army Medical University 2024;46(13):1553-1560
Objective To observe the expression of GLIS3 in triple negative breast cancer(TNBC)and analyze its relationship with the prognosis of TNBC patients.Methods Bioinformatic analysis was applied to analyze the expression level of GLIS3 in Gene Expression Omnibus(GEO).Kaplan-Meier survival curve was plotted to evaluate the impact of GLIS3 expression on the survival rate of patients based on DNA chip data.A total of 125 patients pathologically diagnosed as TNBC in the Fourth Hospital of Hebei Medical University from January to December 2014 were enrolled by cluster random sampling.Among them,53 patients had complete tissue specimens,medical records and follow-up data.Immunohistochemical assay was used to detect the expression of GLIS3 in TNBC and adjacent tissues to tumors,while the relationships between GLIS3 protein expression in breast cancer tissues and clinicopathological parameters such as age,menstrual status,tumor size,clinical stage,histological grade,pathological type,axillary lymph node metastasis,vascular tumor thrombus,and expression of TP53 and Ki-67 were analyzed.Kaplan-Meier survival curve was plotted to analyze the effect of GLIS3 on the overall and disease-free survival of TNBC patients.Cox regression model was established to identify the risk factors impacting the prognosis of the patients.Results Analysis of GEO data showed that the expression of GLIS3 in TNBC was significantly higher than that in paracancer tissues(P<0.05).The expression of GLIS3 was notably higher in the TNBC tissue than the adjacent tissue to tumor(P<0.05).A marked augmentation of GLIS3 expression was observed in both the advanced and larger-sized tumors(P<0.05).Univariate analysis of Cox regression model revealed that lymph node metastasis,TNM stage and GLIS3 expression were all related to disease-free survival of TNBC patients(P<0.05).Univariate and multivariate analyses displayed that TNM stage was related to the overall survival of TNBC patients(P<0.05).The patients with high expression of GLIS3 had significant shorter disease-free survival time than those with low expression(P<0.05),but had no statistical difference in overall survival(P>0.05).Conclusion GLIS3 protein is highly expressed in TNBC tissues,and tumor size and TNM stage are correlated with its high expression.The high expression of GLIS3 suggests that the patients have poor prognosis and low disease-free survival rate.
9.MGMT activated by Wnt pathway promotes cisplatin tolerance through inducing slow-cycling cells and nonhomologous end joining in colorectal cancer
Zhang HAOWEI ; Li QIXIN ; Guo XIAOLONG ; Wu HONG ; Hu CHENHAO ; Liu GAIXIA ; Yu TIANYU ; Hu XIAKE ; Qiu QUANPENG ; Guo GANG ; She JUNJUN ; Chen YINNAN
Journal of Pharmaceutical Analysis 2024;14(6):863-877
Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.
10.Application of perineal single-port robot-assisted radical prostatectomy
Li XU ; Chenhao YU ; Wenjin AN ; Shibin ZHU ; Haiyi HU ; Kangxin NI ; Gonghui LI
Chinese Journal of Urology 2024;45(8):598-602
Objective:To investigate the effect of perineal single-port robot-assisted radical prostatectomy.Methods:A retrospective analysis was conducted on clinical data from 60 patients who underwent perineal single-port robot-assisted laparoscopic radical prostatectomy at our hospital between July 2019 and July 2022. The mean age of the patients was (65.9±7.6) years and the mean BMI was (24.1±2.9) kg/m 2. The median (IQR) prostate volume was 32.7 (23.8, 41.2) ml, and the median (IQR) preoperative PSA value was 8.8 (6.8, 12.6) ng/ml. Preoperative pathology revealed a Gleason score of 6 in 21 patients, Gleason score of 7 in 35 patients and Gleason score of 8 in 4 patients. There were 12 patients clinically staged as T 1 and 48 patients as T 2. A total of 18 patients underwent a total of 23 previous abdominopelvic surgeries. The patient is placed in an exaggerated lithotomy position with the head down and feet elevated approximately 15°. A 3-5 cm incision was made approximately 2 cm above on the mid-perineum between the bilateral ischial tuberosities. Next, the rectourethral muscle was divided, and the space anterior to the rectum was developed by blunt dissection. The levator ani muscles were separated to expose Denonvilliers’ fascia. Then, the disposable multi-channel laparoscopic surgical access system is inserted with a surgical wound protector. Denonvilliers’ fascia was incised transversely and the ampulla of the vas deferens, which were subsequently divided. Blunt separation is performed on both sides along the capsule of the prostate, and then, the vascular pedicles of the prostate are ligated. The membranous urethra was severed after complete urethral separation at the tip of the prostate at the urethral junction. The bladder neck was freed and dissected. The prostate and seminal vesicles were removed and a vesicourethral anastomosis is performed. A perineal drain were left in place. Preoperative and postoperative variables, complications, early urinary continence rate(Return of urinary continence status was defined as using no more than one safety pad per day) and oncological outcomes of patients were recorded. Results:All 60 surgeries were successfully completed without conversions or additional incisions. The median (IQR) total operative time was 200.0(153.8, 236.3) min, the median (IQR) console operating time was 107.5(90.0, 150.0) min and the median (IQR) estimated blood loss was 50.0(50.0, 100.0) ml. Positive surgical margins were detected in five patients (8.3%). The continence rate was 43.1%(22/51), 64.7%(33/51), 92.0%(46/50) and 98.0%(49/50), and the PSA undetectable rate was 94.6%(48/51), 98.2%(49/51), 96.6%(47/50) and 100%(50/50) at the 1, 3, 6, and 12 months after surgery. Only 1(1.7%) patient experienced biochemical recurrence 9 months after surgery. The overall complication rate was 20%, including two cases of acute respiratory distress syndrome, one case of rectal injury, one case of urinary tract injury, two cases of poor wound healing, three cases of incision infection, two cases of urinary tract infection and one case of bladder neck-urethral orifice anastomotic stricture.Conclusions:Perineal single-port robot-assisted radical prostatectomy might be safe and feasible surgical treatments for localized prostate cancer, especially for patients with a history of complex abdominal or pelvic surgery. It also showed advantages in early continence. The anatomical structure of the perineal region should be considered, and the correct incision position should be chosen. Specific incision protection measures should also be used for the incision in this particular area of the perineal region to reduce the risk of perioperative complications.

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