Objective To establish an effective management mode, play the full role of DRGs in rational drug use, formulate the pharmaceutical clinical path, and intervene the prescription behavior of doctors, which could improve the level of rational drug use in the hospital through the management practice of rational drug use under the payment method of DRGs in a third-grade hospital. Methods A drug entering mechanism, a rational drug use supervision mechanism and an active and rational drug use data exposure mechanism based on DRGs were established, and the rational drug use indicators such as drug consumption index, average drug cost, and auxiliary drug use were accurately positioned based on the information platform, and the accurate and refined management of rational drug use was realized through the daily supervision of the office of the Pharmaceutical Affairs Committee. Results and Conclusion Under the multi-dimensional and multi-level rational drug use management based on DRGs, the effect of rational drug use was evaluated after the reform of DRGs payment method, and all the index of rational drug use in our hospital were continuously improved.

OBJECTIVE To investigate the effects of soybean isoflavones （SI） on the reproductive development of young mice. METHODS C57BL/6 young mice were randomly divided into control group， SI low-dose and high-dose groups （10， 100 mg/kg）， with 10 mice in each group （half male and half female）. The young mice in each group were given corresponding liquid intragastrically， once a day， for 2 consecutive weeks. After the last administration， the percentage of body weight increase was calculated； serum estradiol and testosterone levels， malondialdehyde （MDA） content， total antioxidant capacity （T-AOC）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activities in the reproductive organs of the young mice were determined. The histopathological changes in the reproductive organs were observed. The cell apoptosis of reproductive organs was detected. RESULTS Compared with the control group， the percentage of body weight increase in female mice was increased significantly in the SI high-dose group， while that of male mice was decreased significantly （P＜0.05 or P＜0.01）. Cystic follicles could be seen in the ovarian tissue in SI groups， a loose arrangement of spermatocytes could be seen in the testicular tissue， and partial epithelial cell shedding could be seen in epididymal tissue. The serum level of testosterone in female young mice and the serum levels of testosterone and estradiol in male young mice in SI groups， GSH-Px activity in the ovarian tissue of female young mice in the SI low-dose group， T-AOC activities in the ovarian tissue of female young mice in SI groups as well as the apoptotic rates of cells in testicular and epididymal tissue of male young mice in SI groups were increased significantly （P＜0.05 or P＜ 0.01）； the serum level of estradiol in female young mice in SI groups， SOD activity in the ovarian tissue of female young mice in the SI high-dose group， and MDA contents in the ovarian tissue of female young mice in SI groups as well as the apoptotic rates of cells in ovarian tissue of female mice in SI groups were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS SI can enhance the antioxidant stress capacity of ovarian tissue in female young mice and reduce their oxidative stress damage， but it has certain toxicity to reproductive organs in male mice.

BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.

Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.

Objective:To evaluate the efficacy of neoadjuvant chemoimmunotherapy (NACI) combined with transoral robotic surgery (TORS) in the treatment of locally advanced oropharyngeal squamous cell carcinoma (OPSCC).Methods:This was a retrospective study of 15 patients with locally advanced OPSCC who underwent TORS after neoadjuvant therapy (NAT) at the Department of Otolaryngology-Head and Neck Surgery of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2019 to February 2023. There were 12 males and 3 females, aged 31 to 74 years. Twelve cases were tonsil cancer, and 3 cases were tongue base cancer. There were 11 cases in stage Ⅲ and 4 cases in stage Ⅳ. Two patients received neoadjuvant chemotherapy and 13 patients received NACI, with 2 to 3 cycles, and all patients underwent TORS after multidisciplinary team consultation. The clinicopathological characteristics, surgical outcomes, and oncological results were summarized.Results:All surgeries were successfully completed with negative surgical margins, and no case was required conversion surgery. All patients were fed via nasogastric tubes postoperatively, with a median gastric tube stay of 7 days (range: 2-60 days). No tracheotomy was applied. There were no major complications such as postoperative bleeding. Pathological complete response (pCR) was found in 10 cases (76.9%) among the 13 patients with NACI. The follow-up time was 21 months (range: 10-47 months), and there was no death or distant metastasis. One patient with rT0N3M0 tonsil cancer had local recurrence 5 months after surgery. The 2-year overall survival and 2-year disease-free survival were respectively 100.0% and 93.3% in the 15 patients.Conclusion:NACI combined with TORS provides a safe, effective and minimally invasive treatment for patients with locally advanced oropharyngeal squamous cell carcinoma.

Objective:To investigate the preliminary efficacy of 3D printed individualized genioglossus advancement (GA) for the treatment of obstructive sleep apnea (OSA) in adults with micrognathia.Methods:The OSA patients with retropalatal and retroglossal collapses due to micrognathia underwent 3D printed individualized GA combined with Uvulopalatopharyngoplasty(UPPP) in Department of Otolaryngology, Head and Neck Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Clinical data including pre-and post-operative polysomnography (PSG), cephalometric measurements of genioglossus advancement, patient-reported symptom and surgical complications were collected. A comparison of pre-and post-operative data was conducted using paired t-tests. Results:Nineteen OSA patients with micrognathia successfully underwent 3D printed individualized GA combined with UPPP, and achieved an actual mean genioglossus advancement distance of (9.0±1.4) mm compared to the planned distance of (9.4±1.0) mm preoperatively ( t=0.81, P=0.427). Among the 14 patients followed up for more than 6 months, the mean AHI reduced by 60.4% at 6 months postoperatively, with 5 cases (5/14) cured and 5 cases (5/14) showing significant improvement, resulting in an overall surgical response rate of 10/14. All patients expressed satisfaction with their postoperative facial appearance, with 13 cases perceiving an improvement in attractiveness. Two patients reported temporary genial numbness, and one patient experienced temporary mandibular occlusal asthenia. Conclusion:The 3D printed individualized GA combined with UPPP effectively reduces AHI in adult OSA patients with micrognathia, accompanied by a low incidence of surgical complications and high patient satisfaction regarding postoperative facial appearance.

Objective To investigate the protective effects of HTD4010 against lipopolysaccharide(LPS)-induced septic cardiomyopathy(SCM)in mice and explore the mechanisms mediating its effect.Methods Forty-five male ICR mice were randomized equally into control group,LPS(10 mg/kg)group,and LPS+HTD4010 group(in which 2.5 mg/kg HTD4010 was injected subcutaneously at 1 h and 6 h after LPS injection).Cardiac function of the mice was evaluated by ultrasound,and pathological changes in the myocardial tissues were observed with HE staining.The levels of IL-6 and TNF-α in serum and myocardial tissues were detected using ELISA,and apoptosis of the cardiomyocytes was detected with TUNEL staining.The expression levels of the key proteins associated with apoptosis,autophagy and the AMPK/mTOR pathway in the myocardial tissues were detected using Western blotting.The ultrastructural changes of cardiac myocardial mitochondria was observed with transmission electron microscopy.Results LPS exposure caused severe myocardial damage in mice,characterized by myocardial fiber rupture,structural disorder,inflammatory cell infiltration,and mitochondrial damage.The LPS-treated mice exhibited significantly decreased cardiac LVEF and FS values,elevated IL-6 and TNF-αlevels in serum and myocardial tissue,and an increased myocardial cell apoptosis rate with enhanced expressions of Bax,p-62 and p-mTOR and lowered expressions of Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK(P<0.05 or 0.01).Treatment of the septic mice with HTD4010 significantly alleviated myocardial damage,increased LVEF and FS values,reduced IL-6 and TNF-α levels in serum and myocardial tissue,decreased cardiomyocyte apoptosis,lowered myocardial expressions of Bax,p-62 and p-mTOR,and increased Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK expressions(P<0.05 or 0.01).Conclusion HTD4010 can attenuate myocardial injury in SCM mice possibly by promoting autophagy via modulating the AMPK/mTOR signaling pathway.

Objective To investigate the protective effects of HTD4010 against lipopolysaccharide(LPS)-induced septic cardiomyopathy(SCM)in mice and explore the mechanisms mediating its effect.Methods Forty-five male ICR mice were randomized equally into control group,LPS(10 mg/kg)group,and LPS+HTD4010 group(in which 2.5 mg/kg HTD4010 was injected subcutaneously at 1 h and 6 h after LPS injection).Cardiac function of the mice was evaluated by ultrasound,and pathological changes in the myocardial tissues were observed with HE staining.The levels of IL-6 and TNF-α in serum and myocardial tissues were detected using ELISA,and apoptosis of the cardiomyocytes was detected with TUNEL staining.The expression levels of the key proteins associated with apoptosis,autophagy and the AMPK/mTOR pathway in the myocardial tissues were detected using Western blotting.The ultrastructural changes of cardiac myocardial mitochondria was observed with transmission electron microscopy.Results LPS exposure caused severe myocardial damage in mice,characterized by myocardial fiber rupture,structural disorder,inflammatory cell infiltration,and mitochondrial damage.The LPS-treated mice exhibited significantly decreased cardiac LVEF and FS values,elevated IL-6 and TNF-αlevels in serum and myocardial tissue,and an increased myocardial cell apoptosis rate with enhanced expressions of Bax,p-62 and p-mTOR and lowered expressions of Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK(P<0.05 or 0.01).Treatment of the septic mice with HTD4010 significantly alleviated myocardial damage,increased LVEF and FS values,reduced IL-6 and TNF-α levels in serum and myocardial tissue,decreased cardiomyocyte apoptosis,lowered myocardial expressions of Bax,p-62 and p-mTOR,and increased Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK expressions(P<0.05 or 0.01).Conclusion HTD4010 can attenuate myocardial injury in SCM mice possibly by promoting autophagy via modulating the AMPK/mTOR signaling pathway.

Background::Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI.Methods::TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. Results::TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. Conclusion::TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear. METHODS: We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups. RESULTS: Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga . CONCLUSIONS Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.
Humans ; Gastrointestinal Microbiome/genetics* ; Diabetes Mellitus, Type 2 ; Microbiota ; Bacteria/genetics* ; Fatty Acids, Volatile ; Colorectal Neoplasms/metabolism* ; Butyrates ; Feces/microbiology*