ObjectiveTo explore the value of the Model for End-Stage Liver Disease （MELD） 3.0 in predicting survival outcomes for patients with alcoholic cirrhosis and to establish an effective mortality prediction model. MethodsClinical data of 788 hospitalized patients who were first diagnosed with alcoholic cirrhosis at the Third Affiliated Hospital of Sun Yat-sen University between January 1， 2011 and December 31， 2019 were analyzed. Patients were followed up until December 31， 2023 and divided into survival and mortality groups based on the survival outcomes at 30 days， 90 days， 1 year， and 3 years after admission. The prognostic values of the MELD 3.0， MELD， MELD-Sodium （MELD-Na） for survival in alcoholic cirrhosis patients were assessed and compared by using the receiver operating characteristic （ROC） curve and the area under the curve （AUC）. Additional risk factors associated with mortality in alcoholic cirrhosis patients were identified， and a novel mortality prediction model based on MELD 3.0 was developed. ResultsThe AUC of the MELD 3.0 score in predicting 30-day， 90-day， 1-year， and 3-year survival was 0.823， 0.730， 0.686， and 0.658， respectively， which were superior to those of the MELD-Na （0.802， 0.708， 0.666， and 0.645， respectively） and MELD scores （0.698， 0.668， 0.654， and 0.633， respectively） （all P < 0.05）. MELD 3.0 demonstrated better performance at 30 and 90 days （AVC=0.823，0.730； both P < 0.05） than at 1 year and 3 years （AVC=0.686，0.658； both P < 0.05）. Binary logistic regression combined with LASSO regression indicated that the independent risk factors associated with the 1-year outcome included MELD 3.0， baseline ascites and hepatocellular carcinoma. A survival prediction model was then established with AUC of 0.748， sensitivity of 0.695， and specificity of 0.775. ConclusionsMELD 3.0 has a superior predictive ability for 30-day， 90-day， 1-year， and 3-year survival in patients with alcoholic cirrhosis than MELD-Na and MELD. The prediction model incorporating MELD 3.0， ascites and hepatocellular carcinoma improves the prediction of 1-year survival outcomes for alcoholic cirrhosis patients.

Objective:To study the influences of circular RNA ras homolog family member T1(CircRHOT1)on the prolifera-tion,apoptosis and immune escape of breast cancer cells by regulating the miR-187-3p/sex-determining region Y-box protein 4(SOX4)axis.Methods:Real-time quantitative PCR and Western blot were used to detect the expressions of CircRHOT1,miR-187-3p and SOX4 in human normal breast epithelial cells MCF-10A and breast cancer cells MCF-7,Hs-578T and MDA-MB-231 in vitro;MCF-7 cells cultured in vitro were randomly separated into control group,CircRHOT1 knockdown(transfected with CircRHOT1 siRNA plasmid)group,miR-187-3p mimics(transfected with miR-187-3p mimics)group,co-transfection negative control(transfected with empty plasmid and miR-187-3p inhibitor negative control)group,and CircRHOT1 knockdown+miR-187-3p inhibitor(transfected with CircRHOT1 siRNA plasmid and miR-187-3p inhibitor)group.After grouping and transfection,real-time quantitative PCR and Western blot were used to detect the expressions of CircRHOT1,miR-187-3p and SOX4 in each group;cell proliferation in each group was detected by EdU staining and plate colony formation assay;cell apoptosis in each group was detected by flow cytometry;im-munofluorescence staining was used to detect the ratio of apoptosis-related proteins Bax and Bcl-2(Bax/Bcl-2)expressions in each group.The cells of each group were co-cultured with human peripheral blood lymphocytes and transfected into groups,flow cytometry was used to detect the proportion of activated CD8+T cells in human peripheral blood lymphocytes in each group;the killing rate of human peripheral blood lymphocytes to MCF-7 cells in each group was detected by MTT assay.Dual-luciferase reporter assay was used to detect the targeted regulation of miR-187-3p and miR-187-3p on SOX4 by CircRHOT1 in MCF-7 cells.Results:Compared with human normal breast epithelial cells MCF-10A,human breast cancer MCF-7,Hs-578T and MDA-MB-231 cells had obviously higher protein and mRNA expression of CircRHOT1 and SOX4(P<0.05),and obviously lower expression of miR-187-3p(P<0.05).Com-pared with control group,the protein and mRNA expression of SOX4,EdU positive rate and colony formation rate of cells in Circ-RHOT1 knockdown group and miR-187-3p mimics group decreased(P<0.05),the expression of miR-187-3p,apoptosis rate,Bax/Bcl-2,the proportion of activated CD8+T cells in human peripheral blood lymphocytes and the killing rate on MCF-7 cells increased(P<0.05).Compared with CircRHOT1 knockdown group,there was no obvious difference in the expression of CircRHOT1 in the CircRHOT1 knockdown+miR-187-3p inhibitor group(P>0.05),the protein and mRNA expression of SOX4,EdU positive rate and colony formation rate of cells increased(P<0.05),the expression of miR-187-3p,apoptosis rate,Bax/Bcl-2,the proportion of activated CD8+T cells in human peripheral blood lymphocytes and the killing rate on MCF-7 cells decreased(P<0.05);there was no obvious difference in the indexes of cells in co-transfection negative control group(P>0.05).Conclusion:Knockdown of CircRHOT1 can reduce the expression of SOX4 by up-regulating miR-187-3p,thereby attenuating the proliferative activity of breast cancer cells and promoting their apoptosis.It can also inhibit the activation of CD8+T cells and enhance their cancer cell cytotoxicity,thereby weakening immune evasion of breast cancer cells.

Objective:To examine the correlation between serum Klotho levels and frailty in elderly people.Methods:In this cross-sectional study, 150 community-dwelling elderly people aged 65 years and over were enrolled.Subjects were divided into a frail(n=50, 33.3%), a pre-frail(n=47, 31.3%)and a non-frail(n=53, 35.3%)group based on the Fried phenotype.General participant data, routine laboratory test results, short physical performance battery(SPPB)results and human body composition data were collected.Serum Klotho protein levels were measured by an enzyme-linked immunosorbent assay.The relationship between serum Klotho protein levels and frailty was analyzed by using Spearmen's correlation analysis and Logistic regression analysis.Results:Klotho protein levels were lower in the frail group than in the non-frail group( P=0.001), whereas differences between the frail group and the pre-frail group and between the pre-frail group and the non-frail group were not statistically significant(all P>0.05).When Klotho protein levels were classified into four quartiles, i.e., Q 1, Q 2, Q 3, and Q 4, using three cut-off vales(2.28, 3.52, and 5.09 mg/L), the prevalences of frailty were 51.4%(19/37), 39.5%(15/38), 24.3%(9/37)and 18.4%(7/38), respectively.The prevalence of frailty decreased with increasing Klotho protein levels( χ2=11.204, P=0.011).Spearman correlation analysis showed that the Klotho protein level was negatively correlated with frailty( r=-0.310, P<0.001).Multivariate Logistic regression analysis results showed that age( OR=1.109, 95% CI: 1.011-1.217, P=0.028)and sarcopenia( OR=6.511, 95% CI: 1.279-33.147, P=0.024)were risk factors for frailty, while walking( OR=0.104, 95% CI: 0.033-0.326, P<0.001), a high SPPB score( OR=0.780, 95% CI: 0.627-0.970, P=0.026), and a high Klotho protein level( OR=0.752, 95% CI: 0.581-0.974, P=0.031)were protective factors against frailty. Conclusions:The serum Klotho protein level may be used as a parameter for the assessment of frailty.It is negatively correlated with frailty, suggesting that elderly people with low serum Klotho protein levels are at high risk of developing frailty.

Objective To assess the effect of ultrasonic thyroid artificial intelligence(AI)-assisted diagnostic system(AI-assisted diagnostic system)for diagnosing medullary thyroid carcinoma(MTC)compared with different physicians and taken papillary thyroid carcinoma(PTC)as the controls.Methods Totally 63 MTC,70 PTC and 62 benign thyroid nodules confirmed by pathology were enrolled.AI-assisted diagnostic system was utilized to analyze thyroid nodules and identify the likelihood of malignancy,and the probability value threshold was set at ≥0.40.All thyroid nodules were retrospectively reviewed and categorized by 3 physicians(1 senior physician,1 attending physician and 1 junior physician)according to Chinese thyroid imaging reporting and data system(C-TIRADS).The efficacy of AI-assisted diagnostic system and physicians for diagnosing MTC and PTC were evaluated.Results AI-assisted diagnostic system showed lower sensitivity,specificity,positive predictive value,negative predictive value,accuracy,and area under the curve(AUC)for diagnosing MTC and PTC compared with physicians.Significant differences of AUC were found between senior physician and AI-assisted diagnostic system,as well as between attending physician and AI-assisted diagnostic system for diagnosing MTC and PTC(all P＜0.01),while no significant difference of AUC was between junior physicians and AI-assisted diagnostic system(both P＞0.05).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy and AUC for AI-assisted diagnostic system for diagnosing MTC were all lower than those for diagnosing PTC,but the AUC was not significantly different(P＞0.05).Conclusion Ultrasonic thyroid AI-assisted diagnostic system had relatively high value for diagnosing MTC.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Objective:To investigate the differences in gene expression levels in knee chondrocytes and chondrons in vitro.Methods:The chondrocytes and chondrons were isolated from full thickness of the 8-months ( n=5) rabbit knees cartilage. Chondrons from right knee were enzymatically isolated using 0.3% dispase and 0.2% collagenase-2 with shaking for 3 hours. Chondrocytes were isolated by 0.4% Pronase and 0.025% collagenase-2 from left knee. The mRNA levels in chondrocytes and chondrons were analyzed by quantitative real-time PCR, including matrix proteins [aggrecan(Agg), collagen(Col-2), Col-6A6, Col-10, Col-11], MMPs and inhibitors (MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, TIMP-3), cytoskeletal proteins (Sox-9, vinculin, tubulin, actin), cytokines (IL-β, TNF-α). Analysis was performed using SPSS 16.0 statistical software, and the two-group comparisons were considered as significant by t-test at P<0.05. Results:Compared to the chondrocytes, the Agg [(5.78±0.90) vs (1.89±0.27), t=9.26, P<0.001], Col-2 [(6.29±0.76) vs (3.06±0.60), t=7.46, P<0.001], Col-6A6 [(0.89±0.18) vs (0.22±0.06), t=7.90, P<0.001], Col-10 [(3.83±0.76) vs (1.00±0.26), t=7.88, P<0.001] and TIMP-1 [(1.98±0.85) vs (1.03±0.34), t=2.32, P=0.049], TIMP-2[(3.46±1.50) vs (1.52±1.06), t=2.36, P=0.046], TIMP-3 [(3.96±0.50) vs (1.36±0.18), t=10.94, P<0.001], Sox-9 [(7.09±2.93) vs (3.24±0.77), t=2.84, P=0.022], vinculin [(3.42±1.69) vs (1.46±0.68), t=2.41, P=0.043], tubulin[(9.34±0.71) vs (2.35±0.80), t=14.61, P<0.001] showed higher expression in the chondrons. Compared to the chondrocytes, the MMP-1 [(1.02±0.30) vs (2.67±0.45), t=6.91, P<0.001], MMP-3 [(1.21±0.32) vs (2.52±0.79), t=3.44, P=0.009], MMP-13 [(1.23±0.34) vs (3.42±0.86), t=5.30, P=0.007], IL-1β [(1.02±0.14) vs (2.70±0.49), t=7.37, P<0.001], TNF-α [(0.99±0.08) vs (3.15±0.54), t=8.85, P<0.001] showed lower expression in the chondrons. There were no difference between chondrons and chondrocytes for Col-11, MMP-9, actin ( P>0.05). Conclusion:The gene expression of extracellular matrix components are higher and the gene expression levels of inflammatory factors and MMPs are decreased in chondrons compared with the chondrocytes, suggesting the chondrons have more multiplication potential as seeding cells for tissue-engineered cartilage.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Abstract Female stress urinary incontinence (SUI) is a major global public health problem, and its involuntary urinary leakage may seriously affect patients' quality of life. The pathophysiological changes in muscle, connective and nerve tissues induced by diabetes have been found to be strongly correlated with the development and progression of SUI. This review summarizes the association between diabetes and SUI in women and the underlying pathophysiological mechanisms, so as to provide insights into prevention of SUI among female patients with diabetes.

Objective:To study the stability and influencing factors of potassium iodate iodized salt that can be sold in Jilin Province.Methods:In November 2020, 10 large supermarkets were randomly selected in Jilin Province, and two kinds of potassium iodate iodized salts were randomly selected in each supermarket, with five copies of each kind, a total of 100 samples of iodized salt, and the iodine content was determined by spectrophotometry (iodide-starch blue light method). Iodized salt samples were classified according to different salt species (mine salt, sea salt and lake salt) and different production processes (refined salt and non-refined salt). The salt was stored at room temperature, and the iodine content in the salt was measured at 0, 10 and 20 days after opening the packaging. The iodine content attenuation rates of different salt species and different production processes were compared.Results:The mine salt, sea salt and lake salt in iodized salt samples were 45, 45 and 10 portions, respectively. The iodine contents of the 0th day of storage [(19.89 ± 1.38), (20.62 ± 1.91), (19.78 ± 1.01) mg/kg] were compared, and the difference was not statistically significant ( F = 2.57, P = 0.093). On the 10th day, the iodine content of mine salt was lower than that of sea salt and lake salt, and the differences were statistically significant ( P < 0.05); on the 20th day, the iodine content of mine salt was lower than that of sea salt, and the difference was statistically significant ( P < 0.05). There was a significant difference in the iodine content of mine salt stored at 0, 10 and 20 days ( F = 90.62, P < 0.001). The iodine content of sea salt and lake salt on the 20th day was significantly lower than that on the 0th and 10th day, and the differences were statistically significant ( P < 0.05). The iodine content attenuation rates of mine salt, sea salt and lake salt on the 0 - 10 days was compared with that on the 10 - 20 days, and the differences were statistically significant ( Z = 2.24, 2.94, 2.80, P < 0.05). There was a significant difference in the iodine content attenuation rates of mine salt, sea salt and lake salt during the 0 - 10 days of storage ( Z = 24.05, P < 0.001), there was no statistically significant difference in the iodine content attenuation rates on 10 - 20 days ( Z = 5.86, P = 0.053). There was no significant difference in iodine content attenuation rates between refined salt and non-refined salt on 0 - 10, 10 - 20 days ( Z = 1.16, 0.28, P > 0.05). There was no statistical significant difference in the iodine content attenuation rates of refined salt and non-refined salt on the 0 - 10 days compared with those of 10 - 20 days ( Z = 0.76, 1.90, P > 0.05). Conclusions:Iodine loss occurs at 20 days after opening the packaging of iodized salt in Jilin Province. The attenuation of iodine content is less affected by salt species and production processes. It is recommended to eat iodized salt within 20 days after opening the packaging.