Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

Objective:To explore the mechanisms of Qianlie Jindan Tablets(QLJD)acting on chronic nonbacterial prostatitis(CNP)in rats based on non-targeted urine metabolomics.Methods:According to the body mass index,we equally randomized 30 eight-week-old male SD rats into a blank control,a CNP model control and a QLJD medication group.We established the CNP model in the latter groups and,from the 4th day of modeling,treated the rats in the blank and model control groups intragastrically with nor-mal saline and those in the QLJD medication group with QLJD suspension,qd,for 30 successive days.Then we detected the changes in the metabolites of the rats by ultra-high-performance liquid chromatography-tandem mass spectrometry,and identified the differential metabolites in different groups by multivariate statistical analysis,followed by functional annotation of the differential metabolites.Results:Eight common metabolites were identified by metabolomics analysis,of which 5 were decreased in the CNP model controls and increased in the QLJD medication group,while the other 3 increased in the former and decreased in the latter group.Creatinine and genistein were important differential metabolites,and the arginine and proline metabolic pathways and isoflavone biosynthesis pathways were the main ones for QLJD acting on CNP.Compared with the blank controls,the model controls showed up-regulated arginine and proline metabolic pathways,increased production of creatinine,down-regulated isoflavone biosynthetic pathway and decreased produc-tion of genistein.The above changes in the model controls were all reversed in the QLJD medication group.Conclusion:QLJD acts effectively on CNP in male rats by regulating L-arginine and proline metabolic pathways,as well as the isoflavone biosynthesis pathway and naringenin metabolism.

Abstract： Objective　To analyze the value and influencing factors of cross-primer isothermal amplification technology(CPA) in clinical screening and diagnosis of tuberculosis (TB). Methods　We collected 543 inpatients in the Second Affiliated Hospital of Hainan Medical College from January 1, 2018 to December 31, 2021, including 179 patients with tuberculosis, 187 patients with pneumonia and 177 patients with other diseases. The patients' sputum, alveolar lavage fluid, pleural effusion and midstream urine were detected by CPA, smear microscopy, culture method and gene detection. The value of CPA detection in the diagnosis of tuberculosis and its influencing factors were evaluated. Statistical analysis was performed using SPSS 26.0. Results　The total positive rate of CPA was 14.4% (78/543), and the positive rate of sputum samples accounted for 29.1% (39/134). Among the 78 cases of CPA positive patients, the tuberculosis group accounted for 69.2% (54/78), followed by pneumonia group 21.8% (17/78), and other diseases group accounted for 9.0% (7/78). Taking CPA test as the reference method, the "sensitivity" of smear microscopy was lower than that of genetic testing and culture, while the "specificity" was higher than that of culture and gene testing, and the "missed diagnosis rate" of smear microscopy was higher than that of genetic testing and culture. CPA test positive was related to gender, ESR and pneumonia. There is a good agreement between CPA test and culture method and gene test (Kappa>0.9), and a moderate agreement between CPA test and smear microscopy (Kappa=0.616). Conclusions　Sputum specimen is the best choice for CPA detection, while the value of pleural effusion detection is relatively limited. Sputum, alveolar lavage fluid and midcourse urine can be used as clinical specimens for screening and diagnosis of "tuberculosis group and other disease group", while sputum can be used for screening and diagnosis of "tuberculosis group and pneumonia group". Gender, ESR and pneumonia are the influencing factors of CPA positive patients. Therefore, CPA testing is worthy of clinical promotion, but more clinical research data are needed.

With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.
Humans ; Aged ; Aged, 80 and over ; Biliary Tract Surgical Procedures ; Gallstones ; Laparoscopy ; Treatment Outcome ; Aging ; Retrospective Studies

Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.

Protein-protein interactions (PPI) are involved in a variety of biological processes, including cell-to-cell interactions, metabolism and development control. The misregulation, post-translational modification and interference of PPI are related to a variety of human diseases, making the regulation of these interactions a very attractive field of drug discovery. In recent years, the interaction between MDM2 and p53 has become a research hotspot, which plays an important role in the treatment of tumors. But unfortunately there are no such inhibitors approved all over the world. In this view, recent advances of MDM2-p53 inhibitors were briefly described and its inhibitors with potential therapeutic activities in clinical studies were introduced.

Background: Pre-existing comorbidities can predict severe disease requiring intensive care unit (ICU) admission among COVID-19 cases. We compared comorbidities, clinical features and other predictive factors between COVID-19 patients requiring ICU admission for intubation/mechanical ventilation and all other COVID-19 cases in Selangor, Malaysia. Methods: Field data collected during the COVID-19 outbreak in Selangor, Malaysia, up to 13 April 2020 were used, comprising socio-demographic characteristics, comorbidities and presenting symptoms of COVID-19 cases. ICU admission was determined from medical records. Multiple logistic regression analysis was performed to identify factors associated with ICU admission requiring intubation/mechanical ventilation among COVID-19 cases. Results: A total of 1287 COVID-19-positive cases were included for analysis. The most common comorbidities were hypertension (15.5%) and diabetes (11.0%). More than one third of cases presented with fever (43.8%) or cough (37.1%). Of the 25 cases that required intubation/mechanical ventilation, 68.0% had hypertension, 88.0% had fever, 40.0% had dyspnoea and 44.0% were lethargic. Multivariate regression showed that cases that required intubation/mechanical ventilation had significantly higher odds of being older (aged 360 years) [adjusted odds ratio (aOR) = 3.9] and having hypertension (aOR = 5.7), fever (aOR = 9.8), dyspnoea (aOR = 9.6) or lethargy (aOR = 7.9) than cases that did not require intubation/mechanical ventilation. Conclusion: The COVID-19 cases in Selangor, Malaysia requiring intubation/mechanical ventilation were significantly older, with a higher proportion of hypertension and symptoms of fever, dyspnoea and lethargy. These risk factors have been reported previously for severe COVID-19 cases, and highlight the role that ageing and underlying comorbidities play in severe outcomes to respiratory disease.

Problem: The novel coronavirus disease 2019 (COVID-19) pandemic adversely affected the preparation of Malaysia’s National Health and Morbidity Survey for 2020 because conducting it would expose data collectors and participants to an increased risk of infection. Context: The survey is nationally representative and community based and is conducted by the Institute for Public Health, part of the National Institutes of Health, to generate health-related evidence and to support the Malaysian Ministry of Health in policymaking. Its planned scope for 2020 was the seroprevalence of communicable diseases such as hepatitis B and C. Action: Additional components were added to the survey to increase its usefulness, including COVID-19 seroprevalence and facial anthropometric studies to ensure respirator fit. The survey’s scale was reduced, and data collection was changed from including only face-to-face interviews to mainly self-administered and telephone interviews. The transmission risk to participants was reduced by screening data collectors before the survey and fortnightly thereafter, using standard droplet and contact precautions, ensuring proper training and monitoring of data collectors, and implementing other administrative infection prevention measures. Outcome: Data were collected from 7 August to 11 October 2020, with 5957 participants recruited. Only 4 out of 12 components of the survey were conducted via face-to-face interview. No COVID-19 cases were reported among data collectors and participants. All participants were given their hepatitis and COVID-19 laboratory test results; 73 participants with hepatitis B and 14 with hepatitis C who had been previously undiagnosed were referred for further case management. Discussion: Preparing and conducting the National Health and Morbidity Survey during the COVID-19 pandemic required careful consideration of the risks and benefits, multiple infection prevention measures, strong leadership and strong stakeholder support to ensure there were no adverse events.

Inntroduction: The rapid spread of the Coronavirus disease 2019 (COVID-19) worldwide has led the World Health Organization to declare COVID-19 outbreak as a pandemic on March 11, 2020. As the local studies on factors leading to the absence or presence of clinical illness among the COVID-19 cases are sparse, the study aims to determine the factors associated with asymptomatic COVID19 patients in Petaling District, Selangor, Malaysia Methods: Data on COVID-19 patients were extracted from the database of confirmed cases in Petaling District Health Office, Selangor, Malaysia from 3rd February 2020 to 30th April 2020. An asymptomatic laboratory-confirmed case is a person infected with COVID-19 who does not develop any symptoms. The study included socio-demographic variables, the detailed information on clinical manifestations and co-morbidity of the patients. Descriptive and multiple logistic regression analyses were conducted to determine the factors associated with asymptomatic patients. Results: The overall COVID-19 patients in Petaling District were 434. Approximately 70% (n= 292) of the patients were symptomatic while 32.7% (n= 142) were asymptomatic. Multivple logistic regression analyses revealed that factors significantly associated with asymptomatic patients were age below 40 years old (aOR: 1.79, 95% CI 1.11, 2.86), non-Malaysians (aOR: 3.22, 95% CI 1.44, 7.19) and local cases (aOR: 2.51, 95% CI 1.42, 4.42). Gender, ethnicity, comorbidity and township were not significantly associated with asymptomatic patients. Conlcusion Approximately one-third of COVID-19 patients were asymptomatic and the risk factors identified were younger age, non-Malaysians and local cases. Rigorous epidemiological investigation is helpful in identifying COVID-19 cases among these group of people who are asymptomatic.

Objective To study protective and therapeutic measures to improve perioperative safety in extremely elderly patients with biliary diseases.Methods A retrospective case-control study was conducted.The clinical data of elderly patients with biliary diseases treated at the Department of General Surgery,Beijing Electric Power Hospital,from July 2013 to December 2018,were collected.According to age,the patients were divided into the high age (HA) group (≥80.0 years) and the middle-low age (MLA) group (60.0～79.0 years).The related indexes of perioperative safety such as preoperative coexisting diseases,functions of liver,kidney,heart and lung,surgical procedures,intraoperative blood loss,operation time,postoperative hospital stay and postoperative hospital stay were analyzed and compared between the two groups.Results Of the 372 included patients,there were 168 males and 204 females,aged 60.0 to 96.0 (72.0 ± 8.6) years.There were 69 elderly patients (37 males and 32 females) aged 80.0 to 96.0 (84.4 ±3.8) years in the HA group.There were 303 patients in the middle and lower age group (131 men and 172 women),aged 60.0 to 79.0(68.4 ±5.8) years (MLA group).(1) Preoperative coexisting diseases were significantly increased in the HA compared with the MLA group (all P ＜ 0.05),including the proportion of coexisting coronary heart disease [34.8％ (24/69) vs.18.5％ (56/303)],hypertension [68.1％ (47/69)vs.46.9％ (142/303)],chronic bronchitis with emphysema [17.4％ (12/69) vs.3.6％ (11/303)],hypoproteinemia [39.1％ (27/69) vs.26.7％ (81/303)],and anemia [42.0％ (29/69) vs.11.9％ (36/303)].(2) Laboratory examinations:the functions of liver,kidney,heart,lung and blood coagulation were significantly worse in the HA compared with the MLA group (P ＜ 0.05).(3) Surgical procedures:the proportion of open cholecystectomy with transcystic common bile duct exploration (OC + OTCBDE) was higher [17.4％ (12/69) vs.6.9％ (21/303)],while laparoscopic cholecystectomy (LC) was lower [43.5％ (30/69) vs.62.7％ (190/303)],in the HA compared with the MLA group (P ＜0.05,totally).(4) Operative effects:the intraoperative blood loss [30.0 (20.0,75.0) ml vs.20.0 (10.0,30.0) ml],operation time [90.0(72.5,137.5) min vs.77.0(55.0,115.0) min],postoperative hospital stay [10.0(6.0,18.0) d vs.7.0(4.0,11.0) d],and length of hospitalization [17.0(11.5,23.0) d vs.13.0(9.0,19.0) d] were significantly increased or prolonged in the HA compared with the MLA group (all P ＜0.05).(5) Postoperative complications:the incidence of postoperative complications was significantly higher [30.4％ (21/69) vs.12.2％ (37/303)] in the HA compared with the MLA group (P ＜ 0.05).(6) Therapeutic outcomes:there was a cure rate of 95.7％ (66/69) in the HA group,and 97.7％ (296/303)in the MLA group.No significant difference in the therapeutic effects was found between the two groups (P ＞ 0.05).Conclusions Operation in extremely elderly patients with biliary diseases is safe and feasible.The key is to take measures such as actively treating preoperative coexisting diseases,strictly mastering operative indications,reasonably selecting surgical procedures,accurately carrying out precise operation,strictly monitoring and dealing with intraoperative emergency,timely preventing and treating postoperative complications,and especially focusing on maintaining cardiopulmonary function during the perioperative period.