Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

Objective To explore the feasibility and clinical outcome of lateral cervical incision via sternocleidomastoid intermuscular approach(SMIA)in the treatment of primary hyperparathyroidism.Methods The clinical data of 64 patients with primary hyperparathyroidism who underwent unilateral parathyroid surgery in the First Affiliated Hospital,School of Medicine of Zhejiang University from January 2019 to June 2022 were retrospectively analyzed.They were divided into lateral cervical incision via sternocleidomastoid intermuscular approach group(SMIA group)and linea alba cervicalis approach group(LACA group)based on the surgical incision and access route.The differences in clinical features,surgery-related outcomes and postoperative functions of the anterior cervical region were compared between the two groups.The EQ-5D-5L scale was used to assess the subjective feeling of postoperative neck discomfort,while the Hollander Wound Assessment Scale was used to assess the clinical outcome of incision healing.Results There were no statistical differences between the two groups of patients in terms of age,gender,intraoperative bleeding,parathyroid hormone or blood calcium levels before and after surgery(P＞0.05).The duration of surgery was significantly shorter in the SMIA group than in the LACA group[(39.77±5.69)min vs.(54.41±4.66)min].There was a statistical difference between the two groups in functional protection of the anterior cervical region at 1 month and 12 months after surgery(1 month,84.67±3.74 vs.79.47±5.38,P＜0.001;12 months,93.80±2.52 vs.89.94±2.39,P＜0.001),and the SMIA group was better than the LACA group.The Hollander Incision Assessment Scale scores of the SMIA group were better than those of the LACA group at 6 months and 12 months after surgery,and the difference was statistically significant(6 months,1.93±0.58 vs.2.41±0.66,P=0.003;12 months,1.03±0.67 vs.1.74±0.62,P＜0.001).Conclusion Parathyroidectomy via sternocleidomastoid intermuscular approach through lateral cervical incision is a simple,safe and effective surgical procedure,which makes it easier to search for parathyroid lesions and shortens the surgical time compared with the traditional incision,and has obvious advantages in the protection of anterior cervical region function.

Objective:To systematically evaluate the efficacy and safety of laparoscopic transcystic approach with micro-incision of the cystic duct confluence in common bile duct exploration (LTM-CBDE) versus laparoscopic common bile duct exploration (LCBDE) for the treatment of choledocholithiasis.Methods:PubMed, Library, Embase, Cochrane, CNKI, VIP, CBMdisc, Wanfang and other databases were searched to collect relevant literature about LTM-CBDE treatment of choledocholithiasis from December 2013 to December 2023. The main observational indexes were operation time, intraoperative bleeding, drainage tube banding time, postoperative gastrointestinal function recovery time, hospitalization time and postoperative complication rate. Meta-analysis was performed using Review Manager 5.4 software.Results:A total of 15 studies were collected, including one in English and 14 in Chinese. Five were randomized controlled clinical trials and 10 were case-control studies. A total of 1 493 patients, including 690 males and 803 females, aged (53.7±9.2) years old. Among them, 732 patients underwent LTM-CBDE as the microdissection group and 761 patients underwent LCBDE as the control group. Compared with the control group, the meta-analysis showed that patients in the microdissection group had a shorter drain banding time ( MD=-3.34, 95% CI: -4.69--1.99, P<0.001), a faster recovery time of postoperative gastrointestinal function ( MD=-0.63, 95% CI: -1.00--0.25, P=0.001), a shorter hospital stay ( MD=-2.18, and 95% CI: -2.79--1.57, P<0.001), and a lower incidence of bile leak ( OR=0.36, 95% CI: 0.22-0.59, P<0.001) and overall complications ( OR=0.28, 95% CI: 0.18-0.42, P<0.001). Conclusion:LTM-CBDE is safer and more effective than LCBDE in the treatment of choledocholithiasis and deserves clinical promotion.

The COVID-19 pandemic has resulted in excess deaths worldwide. Conventional antiviral medicines have been used to relieve the symptoms, with limited therapeutic effect. In contrast, Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect. The current review aims to: 1) uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19; 2) verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis; 3) investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule; and 4) clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs. Numerous bioactive ingredients in Lianhu Qingwen, such as quercetin, naringenin, β-sitosterol, luteolin, and stigmasterol, were identified to target host cytokines, and to regulate the immune defence in response to COVID-19. Genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR) were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19. Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19. Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19. In conclusion, the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed. Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.
Humans ; COVID-19 ; Pandemics ; Drugs, Chinese Herbal/therapeutic use* ; Antiviral Agents/therapeutic use* ; COVID-19 Drug Treatment

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

BACKGROUND: Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia. In addition to systemic immune/inflammatory effects in response to tumor progression, tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss. However, the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood. METHODS: The yki -gut tumors were induced in fruit flies. Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3 (IGFBP-3) treated cells. Immunoblotting was used to display phenotypes of tumor cells and adipocytes. Quantitative polymerase chain reaction (qPCR) analysis was carried out to examine the gene expression levels such as Acc1 , Acly , and Fasn et al . RESULTS: In this study, it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes. IGFBP-3, which is highly expressed in cachectic tumor cells, antagonized insulin/IGF-like signaling (IIS) and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes. Conditioned medium from cachectic tumor cells, such as Capan-1 and C26 cells, contained excessive IGFBP-3 that potently induced lipolysis in adipocytes. Notably, neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes. Furthermore, cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS, ensuring their escape from IGFBP-3-associated growth suppression. Finally, cachectic tumor-derived ImpL2, the IGFBP-3 homolog, also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila . Most importantly, IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients, especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients. CONCLUSION Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.
Humans ; Insulin-Like Growth Factor Binding Protein 3/metabolism* ; Culture Media, Conditioned/pharmacology* ; Cachexia/pathology* ; Gastrointestinal Neoplasms ; Somatomedins/metabolism* ; Insulins/metabolism* ; Lipids

Objective:To study the efficacy and safety of EndoClot polysaccharide hemostatic system (EndoClot PHS) for heparinized arterial hemorrhage of upper digestive tract (Forrest Ⅰa) in animal model.Methods:Twelve experimental pigs were randomly divided into the test group ( n=6) and the control group ( n=6) by simple random grouping method. Gastric arterial hemorrhage models were established. Endoclot PHS and Hemospray were used to spray on the wound to stop bleeding in the test group and the control group respectively. The time of effective hemostasis, the amount of hemostatic particles used, and the blockage of the powder feeding tube and its replacement were compared between the two groups. The survival and complications of experimental pigs were observed after the operation. In 10 days after the operation, the experimental pigs were euthanized for pathological dissection. Results:Spurting or pulsatile bleeding was achieved in all experimental pigs. There were significant differences in the time of effective hemostasis (8.75±0.84 min VS 9.83±0.62 min, t=-2.53, P=0.030) and the amount of hemostatic particles used to achieve effective hemostasis (6.71±0.39 g VS 14.10±1.62 g, t=-10.86, P<0.001) between the test group and the control group. There was no significant difference in the occurence of clogging or the replacement of powder feeding pipes between the two groups (0.64±0.02 times VS 0.67±0.04 times, t=-1.64, P=0.131). In addition, the gas source of the test group was stable, and the visual field under the endoscope was clear. Neither the test group nor the control group had gastric lesions, perforation, or embolism. The blood glucose, blood routine, and liver and kidney functions were normal, and no thrombosis or embolism of the main organs occurred in either group. Conclusion:EndoClot PHS is safe and effective for heparinized upper gastrointestinal arterial hemorrhage (Forrest Ⅰa) in animal models.

Objective:To investigate the clinicopathological characteristics of papillary thyroid microcarcinoma in the isthmus (PTMCI) and the independent risk factors of central lymph node metastasis.Methods:58 consecutive patients with PTMCI admitted from Jan. 2016 to Dec. 2018 (isthmus group) were retrospectively analyzed, including 15 males and 43 females,age (42.93±12.69) years old; According to the specific location of papillary thyroid microcarcinoma (PTMC) in isthmus, PTMCI were subdivided into the right PTMCI and the left PT-MCI 67 patients with a single PTMC located in the unilateral lobe were randomly selected as a control (lobe group) , including 13 cases of male and 54 cases of female, age (47.18±11.34) years old. Index included the patient’s age, gender, tumor diameter, TPOAb, aspect ratio, microcalcification, capsular invasion, lymph node metastasis, surgical methods, operation method, and scope of lymph node dissection. SPSS 21.0 software was used for statistical analysis. The quantitative data of normal distribution was expressed as ± s,and the difference between the two groups was compared by chi-square test.The risk factors of CLNM of the isthmus group were analyzed with univariate chi-square test and multivariate Logistic regression analysis.The difference was statistically significant if P<0.05. Results:Compared with PTMC, PTMCI showed a higher rate of capsule invasion ( P=0.003) ,lymph node metastasis ( P=0.049) ,lymph node metastasis in central region ( P=0.033) ,and surgical methods between the two groups were statistically significant ( P<0.05) ;But PTMCI was significantly lower than PTMC in aspect ratio>1 ( P<0.05) . Univariate analysis showed that capsule invasion ( P=0.001) and microcalcification ( P=0.012) were risk factors for PTMCI lymph node metastasis. Multivariate Logistic regression analysis showed that capsule invasion ( P=0.016) and microcalcification ( P=0.046) were independent risk factors for central lymph node metastasis in PTMCI. Conclusions:Compared with PTMC,PTMCI indicates a higher rate of capsular invasion,lymph node metastasis in prelaryngeal and central lymph node;Compared with PTMC, PTMCI indicates a lower rate of aspect ratio>1; Capsule invasion and microcalcification are independent risk factors for central lymph node metastasis in PTMCI. For patients with the right PTMCI or the left PTMCI and also without capsular invasion and calcification,ipsilateral central lymph node dissection should be considered.

Primary liver cancer (PLC) is one of the most common malignant tumors in China. PLC is characterized by insidious onset, rapid progress, poor quality of life, and short survival time. Notably, current treatment strategies remain unsatisfactory. Traditional Chinese medicines (TCM) have been used to treat a variety of diseases, including liver diseases, for more than 2000 years. In this study, we performed a review of the use frequency and clinical efficacy of TCM in treating PLC. Relevant literature from January 1, 2009, to January 1, 2021 was retrieved from network databases of China National Knowledge Infrastructure (CNKI), Chongqing VIP, Wanfang, PubMed, and SinoMed. The most frequently used TCM and their effi-cacy in PLC treatment were summarized. Based on the inclusion and exclusion criteria, 33 articles were selected. Overall, the efficacy of the combination of TCM and Western medicines in the treatment of PLC was higher than that in the control groups (i.e. treatment with Western medicines alone) (65.11％ vs. 44.31％, P < .05). Among the 33 selected articles, 11 were investigated for TCM preparation (marketed drugs) and 22 for TCM formulas. In total, 102 types of TCM (single herbs) were used to treat PLC. The top five most frequently used TCM were Poria (14.71％), Astragali radix (13.73％), Atractylodis Macrocephalae Rhizoma (12.75％), Bupleuri radix (12.75％), and Glycyrrhizae radix et Rhizoma (11.76％). Of the 102 types of TCM, tonics were the most frequently used categories, followed by heat-clearing medicines, blood-invigorating medicines, and stasis-resolving medicines. Of 207 papers, 174 (84.06％) could not be sub-jected to statistical analysis due to research quality. Further high-quality research on herb sources, for-mula components and dosage, toxicology, and ethics of TCM is necessary. In conclusion, TCM play a promising role in the treatment and management of PLC, although further investigations are warranted.