ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

To summarize the clinical experience of Professor LIU Jinmin in treatment for epilepsy. It is believed that main pathogenesis of epilepsy is yangming failure to close and vital activity loss control， so a therapeutic approach focused on restoring the closure of yangming and regaining vital activity was proposed for the treatment of epilepsy. For excess syndrome， the treatment focuses on draining excess and descending qi， promoting purgation and restoring spirit. When yangming dryness-heat predominates， the approach involves unblock the bowels and regulating the spirit， descending qi and reducing fire， with modified Chengqi Decoction （承气汤） as prescription； when yangming phlegm-fire predominates， the treatment focuses on clearing heat and resolving phlegm， calming mind and suppressing fright， with modified Qingxin Wendan Decoction （清心温胆汤） as prescription； when yangming blood stasis predominates， the approach involves breaking up blood stasis and promoting purgation， eliminating stasis and awakening the mind， with Taoren Chengqi Decoction （桃核承气汤） as prescription. For deficiency syndrome， the treatment emphasizes tonifying deficiency and raising qi， strengthening the stomach and nourishing the spirit. When center qi deficiency and sinking of clear qi of the nutrients from food， the approach involves replenishing and uplifting qi while nourishing vital activity， with modified Liujunzi Decoction （六君子汤） as prescription； when yin deficiency and fluid consumption， the treatment focuses on nourishing stomach and tonifying yin， promoting fluid production and calming the spirit， with modified Maimendong Decoction （麦门冬汤） combined with Yiwei Decoction （益胃汤） as prescriptions. In clinical situations of deficiency-excess complex， it is essential to distinguish the primary condition from the secondary， applying both supplementing and draining methods flexibly to achieve optimal treatment.

OBJECTIVE To study the extraction technology of Sophora flavescens-Phellodendron chinense drug pair and provide a reference for the development of new drugs for the treatment of anorectal diseases. METHODS Using the contents of total alkaloids of S. flavescens （matrine+oxymatrine）， berberine hydrochloride and total flavonoid， and extract yield as evaluation indicators， analytic hierarchy process-entropy weight method was used to calculate the weight coefficient of each indicator， and was combined with Box-Behnken design-response surface method to study the extraction technology of S. flavescens-P. chinense drug pair and verify it. RESULTS The optimal extraction technology of S. flavescens-P. chinense drug pair was immersed in 12-fold amount of 58% ethanol for 30 minutes and extracted twice， each time for 120 minutes. The relative error between the verification experimental results and the predicted value was 1.88%. CONCLUSIONS The obtained extraction technology is stable and feasible and can provide reference for the application of S. flavescens-P. chinense drug pair and development of new drugs.

Objective:To investigate the prognosis and influencing factors of endoscopic surgery for early glottic carcinoma.Methods:In this retrospective study, we applied the Cox proportional hazards regression model and the random survival forest model to analyze the clinical characteristics of 385 patients [362 males, 23 females, age ranging from 33 to 91 years (62.0±9.6)] who visited the Sixth Medical Center of the General Hospital of the People's Liberation Army from January 2009, to December 2022 and diagnosed with early glottic carcinoma, encompassing variables such as age, gender, T stage, surgical approach, pathological typing, etc. The primary evaluation indicators were overall survival(OS) and disease-free survival rates (DFS). The follow-up duration ranged from 30 to 5,557 days (with a median follow-up time of 1,596 days).Results:After a three-year follow-up, the OS rate for the 385 patients was 95.83%, while the DSF rate was 82.98%. The Cox proportional hazards regression analysis revealed age ( HR=2.35, 95% CI: 1.75 to 3.15, P<0.001) and T staging ( HR=1.59, 95% CI: 1.13 to 2.23, P=0.019) as predominant factors affecting the OS and DFS. The random survival forest model identified poor tumor differentiation, and high expression of P53 and Ki-67 as predictors of inferior prognosis. Conclusion:Endoscopic surgery for early glottic carcinoma yields favorable short-term OS and reduces short-term recurrence rates, with T-stage emerging as a pivotal factor influencing recurrence. Tumors with poor differentiation and elevated expression of P53 may be indicative of an increased risk of recurrence.

Objective:To explore the repair methods and effects of refractory wounds in patients after spinal internal fixation operation .Methods:The study was a retrospective observational study. From November 2020 to October 2023, 10 patients with refractory wounds after spinal internal fixation operation were admitted to the Department of Burns and Plastic Surgery of Changde Hospital of Xiangya School of Medicine of Central South University. They were 3 males and 7 females, aged 35 to 68 years. There were 6 cases of thoracolumbar tuberculosis, 3 cases of thoracolumbar fracture, and 1 case of recurrent sacrococcygeal chordoma with skin, soft tissue, and bone defects after radical resection. The wound areas after debridement were 6.0 cm×1.5 cm to 27.0 cm×6.5 cm. The wound repair operation was decided to perform in the primary stage or in the secondary stage according to the wound situation. Two patients with type Ⅰ wounds were treated with debridement, direct suture, and continuous irrigation and drainage with catheter after operation. Eight patients with type Ⅱ wounds were repaired with local flaps (including rotation flap with dermis-fat flap at the end), muscle flaps, or muscle flaps combined with local flaps. The flap sizes were 10.0 cm×5.0 cm to 27.0 cm×14.0 cm, and the sizes of muscle flap were 8.0 cm×5.0 cm×4.0 cm to 17.0 cm×9.5 cm×2.0 cm. The wounds in flap donor areas were sutured directly. The wound treatment methods of patients with type Ⅱ wounds were recorded. The wound healing was observed after operation. The infection and recurrence of wounds, the retention of internal fixation materials, and spinal motor function were observed during follow-up.Results:Among patients with type Ⅱ wounds, there were 3 cases applied with local flaps (including 1 case with rotation flap with dermis-fat flap at the end), 3 cases with muscle flaps (including 1 case with latissimus dorsi muscle flap and 2 cases with erector spinal muscle flaps), and 2 cases with muscle flaps (1 case with latissimus dorsi muscle flap and 1 case with erector spinal muscle flap) combined with local flaps. Only 1 case with secondary defects after radical surgery of sacrococcygeal chordoma had poor wound healing which healed after dressing change, and the wounds of the remaining 9 cases all healed well. During the follow-up of 4 to 18 months, no infection or recurrence of local wounds developed in 10 patients, the internal fixation materials were not loosening, and there was no significant limitation in spinal motor function.Conclusions:For refractory wounds after spinal internal fixation operation, according to the wound type of patients, debridement, suture, irrigation, and drainage in the primary stage, or transplantation of local flaps, muscle flaps, muscle flaps combined with local flaps are performed in the primary stage or in the secondary stage. These methods are proved to have reliable therapeutic effects, not only repairing the wounds, but also retaining the internal fixation materials.

To evaluate the advantages of using PBL case library in teaching circulatory system diseases to clinical medicine undergraduate students, a PBL case library was established and applied in teaching practice in the reform of circulatory system teaching. The PBL case library achieved the characteristics of combining theories with cases, morphology with functions, and basic knowledge with clinical knowledge. The PBL case library also realized the informatization, query, and update of cases. Preliminary application showed that the median practical score of students in the case library group was 94.00 points, which was significantly higher than the 92.00 points in the control group ( P=0.005). The average lesson preparation time for teachers in the case library group was (5.00±1.00) hours, which was significantly shorter than the (6.89±0.42) hours in the control group ( P<0.001). The difficulty score for lesson preparation among teachers in the case library group was significantly lower than that of the control group [(1.89±1.05) vs. (3.22±0.44), P<0.001]. However, there were no significant difference in theoretical scores and student satisfaction with teachers and courses. These results suggest that the construction of case library can improve practical teaching effectiveness and enhance the efficiency of lesson preparation for teachers.

Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53)， P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.

Objective:To explore the strategy of how to select an effective flap for reconstruction of the surgical defect in clavicular region after resection of malignant tumour and care for the aesthetic appearance of the flap donor site.Methods:A retrospective observational study was conducted. Twenty-three patients with soft tissue malignant tumour in clavicle region were treated, from March 2017 to April 2023, in the Department of Burn and Plastic Surgery of Changde Hospital, Xiangya School of Medicine, Central South University (the First People’s Hospital of Changde). The patients were 13 males and 10 females, aged 21 to 72 years old. Ten patients were of dermatofibrosarcoma protuberans, 6 of fibrosarcoma, 3 of squamous cell carcinoma of skin, 3 of undifferentiated pleomorphic sarcoma and 1 of mucinous adenocarcinoma. Nine patients had the first surgery and 14 were with tumour recurrence and had previousely received one or more surgery in other hospitals. The tumour size ranged from 2.0 cm×4.5 cm×1.0 cm to 10.0 cm×16.0 cm×3.0 cm. After radical resection, the sizes of surgical defect ranged from 9.0 cm×12.0 cm to 16.0 cm×22.0 cm. All the clavicular soft tissue malignancies had radical resection, and the secondary surgical defects were further modified to reduce the short and long dimensions of the defects. Flaps were selected according to the short dimension, depth and skin elasticity of the flap donor site. Of the 23 patients, 3 were treated with free inguinal flaps, 9 with ipsilateral pedicled latissimus dorsi flaps or thoracodorsal artery perforator flaps, 5 with free deep inferior epigastric artery perforator flap (DIEPF), 5 with free anterolateral thigh flap (ALTF) and 1 with free rectus abdominis flap. The modified defects sized 5.0 cm × 11.0 cm-12.0 cm×19.0 cm after the suture of margin and base of the defects (defects were reduced and modified). The flap sizes were 7.0 cm×13.0 cm-14.0 cm×23.0 cm. After surgery, the wound healing was observed through the visits of outpatient clinic, and telephone and WeChat interviews. According to the nature of the tumours, the patients were regularly reviewed at outpatient clinic to determine the local recurrence and metastasis of the tumour.Results:One pedicled latissimus dorsi myocutaneous flap was found with a greater tension after surgery. After partial removal of sutures and dressing changes, the secondary suture was performed 1 week later and the wound healed smoothly. A postoperative venous crisis was discovered in a free ALTF. It was monitored and re-anastomosed within 24 hours after surgery, and the flap survived and the wound healed smoothly. Otherwise, the rest of flaps achieved good blood supply and the wounds at the recipient and donor sites healed in one stage. In the postoperative follow-up, all flaps in the clavicular region were found good in appearance with no obvious swelling, and the donor sites healed well without scar contracture or dysfunction. One patient with a squamous cell carcinoma died of lung metastasis at 13 months after surgery. The rest of patients were found no tumour recurrence and had completed postoperative follow-up.Conclusion:After radical resection of malignant soft tissue tumours in the clavicular region, appropriate flaps were selected according to the size (short diameter) and depth of the modified defects, as well as the skin elasticity and relaxation of the flap donor site, hence to facilitate the direct suture of the flap donor site. It not only effectively reconstructs the surgical defect in clavicular region, but also minimises the damage to the flap donor site and achieves an aesthetic appearance at the flap donor site.

Objective:To explore the risk factors of hospital death in patients with acute Upper gastrointestinal bleeding, analyze the role of emergency endoscopy, and provide reference for grass-roots hospitals to carry out related work.Methods:A total of 370 patients with acute Upper gastrointestinal bleeding hospitalized in the Xinghua People′s Hospital from January to December 2022 were included, 278 of whom underwent emergency gastroscopy. The common causes and locations of acute Upper gastrointestinal bleeding were analyzed, and the influencing factors of death from acute upper gastrointestinal bleeding were analyzed by logistic regression.Results:Among 370 patients with acute Upper gastrointestinal bleeding, the majority were male [67.3%(249/370)], the median age was 70(57-78)years old, and the median hemoglobin level at admission was 72(57-96)g/L. Among them, 278 patients underwent gastroscopy, and 130 patients received blood transfusion treatment of 2(1.5-3.5)units of red blood cells transfusion. The median length of stay was 5(4-7)days. The age of the endoscopic group was younger than that of the non endoscopic group ( P<0.001), and the hemoglobin level was higher than that of the non endoscopic group ( P<0.001). The proportion of hemostatic drug use and blood transfusion was lower than that of the non endoscopic group ( P=0.027, P<0.001). In patients undergoing gastroscopy, the causes of upper gastrointestinal bleeding included 144 cases (51.8%) of ulcer related bleeding, 61 cases (22.0%) of bleeding caused by acute mucosal lesions, 27 cases (9.7%) of bleeding caused by tumors, 12 cases (4.3%) of bleeding caused by cardiac tears, 5 cases (1.8%) of bleeding caused by vascular malformations, and 29 cases (10.4%) of bleeding caused by varices. The bleeding sites included: 170 cases (61.1%) had bleeding from the stomach, 53 cases (19.1%) from the esophagus, 54 cases (19.4%) from the duodenum, and 1 case (0.4%) from gastroduodenal compound ulcer bleeding. Among all patients, 19 died in the hospital, and among 92 patients who did not undergo emergency gastroscopy, 16 died, with a mortality rate of 17.4%; Among 278 patients who underwent emergency gastroscopy, 3 died, with a mortality rate of 1.08%. Logistic single factor regression analysis found that the elderly (>70 years old), low hemoglobin (<70 g/L), blood transfusion and emergency gastroscopy were the influencing factors of hospital death in patients with acute upper gastrointestinal bleeding. Multivariate regression analysis showed that emergency gastroscopy ( OR=0.043, 95% CI: 0.010-0.198, P<0.001) could reduce the hospital death of patients with acute upper gastrointestinal bleeding. Conclusions:Acute upper gastrointestinal bleeding is common in elderly patients. On the basis of stable hemodynamics and early endoscopic examination, identifying the cause and combining traditional drugs for endoscopic hemostasis can improve the prognosis of patients and reduce the mortality of acute upper gastrointestinal bleeding.

Lung cancer is one of the most common cancers in the world, and its treatment strategy is mainly surgery combined with radiotherapy and chemotherapy. However, long-term chemotherapy will result in drug resistance, which is also one of the difficulties in the treatment of lung cancer. Ferroptosis is an iron-dependent and lipid peroxidation-driven non-apoptotic cell death cascade, occurring when there is an imbalance of redox homeostasis in the cell. Nuclear factor erythroid 2-related factor 2 (Nrf2) is key for cellular antioxidant responses. Numerous studies suggest that Nrf2 assumes an extremely important role in regulation of ferroptosis, for its various functions in iron, lipid, and amino acid metabolism, and so on. In this review, a brief overview of the research progress of ferroptosis over the past decade will be presented. In particular, the mechanism of ferroptosis and the regulation of ferroptosis by Nrf2 will be discussed, as well as the role of the Nrf2 pathway and ferroptosis in tumor drug resistance, which will provide new research directions for the treatment of drug-resistant lung cancer patients.
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Humans ; Ferroptosis ; NF-E2-Related Factor 2/genetics* ; Lung Neoplasms/genetics* ; Drug Resistance, Neoplasm ; Iron