Heterozygous Variants in KCNJ10 Cause Paroxysmal Kinesigenic Dyskinesia Via Haploinsufficiency.

OBJECTIVE: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients. METHODS: Whole-exome sequencing was performed for 106 PRRT2-negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila. RESULTS: Heterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2-negative probands. Both co-segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation-carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes. INTERPRETATION: Our study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024.

Effects of the nutrient inhibition on the yield of DBPFPs by Microcystis aeruginosa.

The yield of three disinfection byproduct formation potentials (DBPFPs), including trichloromethane, dichloroacetic acid and trichloroacetic acid formation potential (TCMFP, DCAAFP and TCAAFP), by Microcystis aeruginosa under the nitrate and phosphate inhibition conditions was investigated. The results showed that excessive nitrate could inhibit the growth of M. aeruginosa, but the concentration of DBPFPs in the five fractions of algal metabolites, including hydrophilic extracellular organic matter (EOM), hydrophobic EOM, hydrophilic intracellular organic matter, hydrophobic intracellular organic matter and cell debris, only decreased slightly. Accordingly, the productivity of DBPFPs by M. aeruginosa increased by approximately 40% under the nitrate inhibition condition and the increased productivity of DBPFPs mainly came from EOM. The phosphate inhibition also performed a similar pattern with a lesser extent. The nutrient inhibition did not change the proportion of these three DPBFPs, and TCMFP accounted for approximately 87% of the total DBPFPs. The inhibition could promote M. aeruginosa to secrete more metabolites. However, the cyanobacteria tended to secrete more DBPFPs under the nitrate inhibition condition, which resulted in an increased specific DBPFP, while they tended to secrete more non-DBPFPs under the phosphate inhibition condition, which resulted in a decreased specific DBPFP.

Exploration of a nomogram prediction model of 30-day survival in adult ECMO patients.

Objective: To investigate the factors of 30-day survival in ECMO patients, establish a nomogram model, and evaluate the predictive value of the model. Methods: A total of 105 patients with extracorporeal membrane oxygenation (ECMO) were admitted to the Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, from January 2018 to March 2021. Cox regression analysis screened out the risk factors. Based on the results of multivariate analysis, the nomogram model was established by using R software, and the discrimination of the model was verified by bootstrap and calibration. Results: The results showed that sex, acute physiology and chronic health evaluation (APACHE) II score, disseminated intravascular coagulation (DIC) score before ECMO initiation and average daily dose of norepinephrine were independent risk factors for prognosis. Verify that the nomogram model is verified by bootstrap internally, and the corrected C-index is C-index: 0.886, showing a good degree of discrimination. The calibration curve (calibration) showed that the nomogram model had good agreement. The decision curve analysis(DCA) curve shows good clinical validity above the two extreme curves. Kaplan-Meier curves were drawn for patients in the tertile and compared with the first and second groups. The third group predicted the worst 30-day prognosis for ECMO patients. Conclusion: The nomogram prediction model constructed based on the sex, APACHE II and DIC score, average daily dose of norepinephrine can effectively screen out the factors affecting the prognosis and provide a reference for individualized treatment of ECMO patients.

Suppression of SMOC2 alleviates myocardial fibrosis via the ILK/p38 pathway.

Background: Fibrosis of the myocardium is one of the main pathological changes of adverse cardiac remodeling, which is associated with unsatisfactory outcomes in patients with heart disease. Further investigations into the precise molecular mechanisms of cardiac fibrosis are urgently required to seek alternative therapeutic strategies for individuals suffering from heart failure. SMOC2 has been shown to be essential to exert key pathophysiological roles in various physiological processes in vivo, possibly contributing to the pathogenesis of fibrosis. A study investigating the relationship between SMOC2 and myocardial fibrosis has yet to be conducted. Methods: Mice received a continuous ISO injection subcutaneously to induce cardiac fibrosis, and down-regulation of SMOC2 was achieved by adeno-associated virus-9 (AAV9)-mediated shRNA knockdown. Neonatal fibroblasts were separated and cultured in vitro with TGFß to trigger fibrosis and infected with either sh-SMOC2 or sh-RNA as a control. The role and mechanisms of SMOC2 in myocardial fibrosis were further examined and analyzed. Results: SMOC2 knockdown partially reversed cardiac functional impairment and cardiac fibrosis in vivo after 21 consecutive days of ISO injection. We further demonstrated that targeting SMOC2 expression effectively slowed down the trans-differentiation and collagen deposition of cardiac fibroblasts stimulated by TGFß. Mechanistically, targeting SMOC2 expression inhibited the induction of ILK and p38 in vivo and in vitro, and ILK overexpression increased p38 phosphorylation activity and compromised the protective effects of sh-SMOC2-mediated cardiac fibrosis. Conclusion: Therapeutic SMOC2 silencing alleviated cardiac fibrosis through inhibition of the ILK/p38 signaling, providing a preventative and control strategy for cardiac remodeling management in clinical practice.

Identification and expression analysis of the ZRT, IRT-like protein (ZIP) gene family in Camellia sinensis (L.) O. Kuntze.

The ZRT, IRT-like protein (ZIP) family plays an essential role in the homeostasis of zinc and iron in plants. However, studies on this family are mainly limited to model species. Here, 12 CsZIPs were identified and investigated the function in Camellia sinensis, being named CsZIP1-12 and divided into four different groups based on phylogenetic relationships. These CsZIPs contained 2-9 TMDs and other conserved motifs for ZIP proteins. And CsZIPs were located in cell membrane, excepting for CsZIP4 and CsZIP6. The expression of CsZIPs were different in varieties and organs of tea plants. They were involved in the response process of abiotic stresses, such as NaCl, drought, cold and exogenous Me-JA. In addition, 31 types of promoter elements were identified in the CsZIPs, including core promoters, light responsiveness, stress responsive and other elements. The CsZIP1, CsZIP2, CsZIP4, CsZIP5, CsZIP6, CsZIP11 and CsZIP12 could be induced by zinc deficiency and 50 µM Zn treatment, but CsZIP7 and CsZIP8 were up regulated by 300 µM Zn. Heterogeneous complementation analysis showed that CsZIP1, CsZIP2, CsZIP7 and CsZIP8 could complement the Zn sensitivity of △zrc1cot1 yeast double mutant. There was a positive correlation between the expression of CsZIPs and secondary metabolites in tea plant. Together, our analysis of CsZIPs could provide comprehensive insights on the structure and function of this protein family in the regulation of zinc and ion homeostasis in the tea plant.

Performing Precise Biopsy in Naive Patients With Equivocal PI-RADS, Version 2, Score 3, Lesions: An MRI-based Nomogram to Avoid Unnecessary Surgical Intervention.

PURPOSE: The primary objective of the present study was to avoid unnecessary prostate biopsy in biopsy-naive patients with Prostate Imaging Reporting and Data System, version 2 (PI-RADS v2), score 3, lesions. MATERIALS AND METHODS: We reviewed our prospectively maintained database from January 2012 to July 2018. Logistic regression analyses were performed to test different clinical factors as predictors of clinically significant prostate cancer (CSPCa) and build nomograms. Calibration curves were used to assess the concordance between the predictive value and the true risk. Decision curves were created to measure the overall net benefit. RESULTS: The prostate cancer (PCa) and CSPCa detection rates were 37.2% (81 of 218) and 23.9% (52 of 218) in the PI-RADS v2, score 3, cohort. More PCa cases (61.7%; 50 of 81) and CSPCa cases (75%; 39 of 52) were found in the peripheral zone than in the transitional zone. Multivariate analysis showed that age, prostate-specific antigen density, lesion region, and apparent diffusion coefficient (ADC) were predictive factors for CSPCa and PCa. Internally validated calibration curves showed that the predicted risk of CSPCa was closer to the actual probability when the threshold was > 60%. Decision curves showed that a better net benefit was achieved when the model was used to guide clinical practice. CONCLUSIONS: More cases of PCa and CSPCa were seen in the peripheral zone than in the transitional zone among patients with PI-RADS v2, score 3. The positive predictive value for a positive ADC (< 900 µm2/s) for the detection of CSPCa and PCa improved with an increasing prostate-specific antigen density. Biopsy can be avoided if the equivocal lesion has a negative ADC (> 900 µm2/s) and was in the transition zone.

Auxiliary diagnostic value of T cells spot test of Mycobacterium tuberculosis infection for pulmonary and extra-pulmonary tuberculosis among the elderly / 中国血吸虫病防治杂志

Objective To evaluate the auxiliary diagnostic value of T cells spot test of Mycobacterium tuberculosis infection (T-SPOT.TB) for pulmonary and extra-pulmonary tuberculosis among the elderly. Methods A total of 173 elderly patients at ages of 60 years and older and with suspected tuberculosis that were admitted to People’s Hospital of Xinjiang Uygur Autonomous Region during the period from October 2022 through February 2024 were enrolled, and all patients underwent T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests. The etiological tests of MTB served as a gold standard, and the diagnostic values of T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests for pulmonary and extra-pulmonary tuberculosis were compared among the elderly patients. Results Of the 173 elderly patients suspected of tuberculosis, there were 44 patients definitely diagnosed with pulmonary tuberculosis, 30 cases with extra-pulmonary tuberculosis, and 99 cases without tuberculosis. The sensitivities of T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests were 86.5%, 27.0% and 54.1% for diagnosis of tuberculosis. The sensitivities of T-SPOT.TB were 86.4% and 86.7% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with an 80.8% specificity for diagnosis of tuberculosis. The sensitivities of GeneXpert MTB/RIF were 56.8% and 50.0% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with a 100.0% specificity each, and the sensitivities of acid fast staining were 31.8% and 20.0% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with a 100.0% specificity each. In addition, the areas under the receiver operating characteristic curve were 0.836, 0.635 and 0.770 for diagnosis of tuberculosis with T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests among the elderly patients, respectively. Conclusion T-SPOT.TB has a high auxiliary diagnostic value for both pulmonary and extra-pulmonary tuberculosis among elderly patients.

Visualization of the biomechanical characteristics of long-distance running landing patterns / 中国组织工程研究

BACKGROUND:In recent years,as the popularity of long-distance fitness running continues to rise,more research progress has been made on related scientific issues.Among them,the landing pattern of long-distance running is an important biomechanical research hotspot at the level of running technique. OBJECTIVE:Using CiteSpace to visualize and analyze the relevant literature,the article sorts through the last decade's literature on the subject to identify the current state,hot spots,and trends in the footprint as well as to further discuss the main research hotspots of the foot strike pattern from a biomechanical perspective. METHODS:"Foot strike pattern,""Rearfoot strike,""non-Rearfoot strike,""Forefoot strike"and"Midfoot strike"were used as keywords to search the Web of Science Core Collection database. RESULTS AND CONCLUSION:A total of 896 relevant papers were finally included.The number of articles published in a year showed an overall upward trend.The top three countries in terms of the number of publications were the United States,China and the United Kingdom;the top three institutions were Harvard University,Shanghai University of Sports and the University of Massachusetts;and the top three authors were Davis Irene S,Hamill Joseph and Fu Weijie.The keywords"barefoot running,runner,injury,footing pattern,kinesiology"appear more frequently,and the keyword clusters include"energy cost,loading rate,footing pattern,risk factors,gait analysis",and the relevant research still continues to be hot to this day.After analyzing the above data in detail,we found that the overall research intensity of foot strike pattern has remained stable in recent years,and the hotspot mainly focuses on the biomechanical research of foot strike pattern;the trend of this kind of research focuses on the influence and adaptability of different strike patterns(forefoot strike and rearfoot strike)on long-distance runners(barefoot,shoes,distance,speed,injury risk,running economy and energy consumption,etc.).Therefore,there is no"standardized optimal landing,"but there may be"individualized optimal landings."It is suggested that researchers should select the optimal landing pattern and running technique strategy according to their own habitual way,movement pattern characteristics,exercise level and task attributes.

The association between vitamin intake and the progression of metabolic dysfunction-associated fatty liver disease / 实用医学杂志

Objective There is a Few studies explored the association between vitamin intake and meta-bolic dysfunction-associated fatty liver disease(MAFLD),while the existing results were still contradictory.This study aimed to investigate the association between dietary vitamins and all-cause mortality as well as fibrosis risk in patients with MAFLD.Methods The data were extracted from the third National Health and Nutrition Examination Surveys 1988-1994.Dietary vitamins was assessed using a 24 h diet recall,including vitamin A,vitamin B6,vitamin B12,vitamin C,vitamin D,thiamin,riboflavin,folic acid and α-tocopherol.The non-alcoholic fatty liver disease fibrosis score(NFS)<-1.455 was considered as non-advanced fibrosis,while NFS≥-1.455 was considered as advanced fibrosis.Results A total of 3844 MAFLD participants were included in this study.The median time of follow-up was 310 months.1739 participants(45.3%)were deceased during the follow-up.The intake of thiamin,riboflavin,α-tocopherol,VB6,and VB12 were significantly higher in patients with NFS-determined non-advanced fibrosis(P<0.05).After adjusting,a significantly lower risk of fibrosis was found in patients with the highest quartile(>11.5 mg/d)of α-tocopherol intake compared to the lowest intake group(P = 0.031).Compared to the lowest quartile group,the risk of mortality was reduced by 0.34 folds in the group consuming the highest quartile amount(>130 mg/d)of VC(HRs:0.66,95%CI:0.51～0.85,P = 0.001).Conclusions More α-tocopherol intake reduced fibrosis grade in MAFLD patients.VC intake may reduce all-cause mortality in patients with MAFLD.

Clinical study of intensity-modulated radiation therapy combined with camrelizumab in the treatment of advanced hepatocellular carcinoma / 局解手术学杂志

Objective To investigate the efficacy and safety of intensity-modulated radiation therapy combined with camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods A total of 84 patients with advanced HCC admitted to our hospital from January to December 2020 were selected as the study objects,and were randomly divided into the observation group and the control group,with 42 cases in each group.Patients in the observation group received intensity-modulated radiation therapy combined with carrelli-zumab,and patients in the control group received intensity-modulated radiation therapy.The short-term efficacy,immune function and long-term survival rate of patietns in the two groups were compared,and the incidence of adverse reactions was recorded.Results The total effec-tive rates of the observation group 1 month and 3 months after treatment were significantly higher than those of the control group(P<0.05).The levels of CD3+,CD4+ and CD4+/CD8+ 1 month and 3 months after treatment were all increased in the two groups,while the levels of CD8+ in both two groups were decreased(P<0.05),and the levels of CD3+,CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group(P<0.05),and the levels of CD8+ in the observation group were lower than those in the control group(P<0.05).The median survival time of patients in the observation group was significantly longer than that of patients in the control group(P<0.05).The incidence of cutaneous capillary hyperplasia in the observation group was higher than that in the control group(P<0.001),and there was no significant difference in the incidence of other adverse reactions between the two groups(P>0.05),and all of adverse reactions were grades 1 to 2.Conclusion Intensity-modulated radiation therapy combined with camrelizumab has a good effect on HCC,it can improve the immune function of the body,and control the development of the disease,with good safety.

Role of NLRP3 Inflammasome in IgA Nephropathy and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

IgA nephropathy is recognized as the most common primary glomerular disease， with up to 20%-40% of patients developing end-stage kidney disease within 20 years of onset. The deposition of IgA1-containing immune complexes targeting glycosylation defects in the mesangial region and the subsequent inflammation caused by T lymphocyte activation are considered as the main causes of IgA nephropathy， and innate immunity is also involved in the pathogenesis. Nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） is a newly discovered pattern recognition receptor expressed in renal intrinsic cells such as renal tubular epithelial cells， mesangial cells， and podocytes. Activated by external stimuli， NLRP3 can form NLRP3 inflammasomes with apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC）. The NLRP3 inflammasome can activate cysteine aspartate-specific protease-1 （Caspase-1）， causing the maturation and release of interleukin-18 （IL-18） and interleukin-1β （IL-1β） involved in inflammation. Increasing evidence has suggested that NLRP3 inflammasomes are involved in the pathogenesis and progression of IgA nephropathy and associated with the damage of renal intrinsic cells such as podocytes， mesangial cells， endothelial cells， and renal tubular epithelial cells. Chinese medicine can regulate inflammatory cytokines and their signaling pathways by acting on NLRP3 inflammasomes and related molecules， exerting therapeutic effects on IgA nephropathy. This article introduces the role of NLRP3 inflammasomes in IgA nephropathy and reviews the clinical and experimental research progress of Chinese medicine intervention in IgA nephropathy via NLRP3 inflammasomes， aiming to provide a reference for further research and application of Chinese medicine intervention in the NLRP3 inflammasome as a new therapeutic target.

Chinese Medicines Combined with Hormones in the Treatment of Premature Ovarian Failure:A Network Meta-analysis / 广州中医药大学学报

Objective To screen the optimal regimen of Chinese medicine combined with hormones for the treatment of premature ovarian failure(POF)using network meta-analysis and to provide an evidence-based basis for the clinical treatment of POF.Methods The randomized controlled trials(RCTs)of Chinese medicine combined with hormones in the treatment of POF were retrieved from thhe domestic and oversea databases of CNKI,VIP,Wanfang,CBM,PubMed,Cochrane,Embase,and Web of Science.The quality of the literature was assessed using the tools for analysis of bias recommended by Cochrane Reviewer's Handbook and by Jadad scale scores.Rstudio and StataSE 15.1 statistical software were used to perform network meta-analysis and graphical presentation of the data.Results A total of 50 RCTs were included,covering 8 intervention methods.The overall risk of bias of the included studies was low,but the quality of the literature was generally low.The results of network meta-analysis showed that,in terms of the effective rate,the intervetion of 7 various Chinese medicines combined with hormone was superior to the conventional treatment(hormone replacement therapy,HRT)in the control group,and Nuangong Qiwei Powder+HRT was superior to the remaining 6 kinds of Chinese medicines combined with HRT;with reference to the values of the surface under the cumulative ranking curve(SUCRA),the efficiencies of the effective rate of the 8 intervention methods in descending order were Nuangong Qiwei Powder+ HRT(SUCRA=81.2),Zishen Yutai Pills + HRT(SUCRA=80.0),modified Zuogui Pills + HRT(SUCRA= 66.1),Ankun Zhongzi Pills + HRT(SUCRA=49.6),Kuntai Capsules + HRT(SUCRA=45.2),modified Erxian Decoction + HRT(SUCRA=39.5),Liuwei Dihuang Pills + HRT(SUCRA=37.4)and HRT(SUCRA=1.0).In terms of improving serum follicle-stimulating hormone(FSH)levels,modified Zuogui Pills + HRT was superior to the remaining 7 intervention methods;with reference to the values of the SUCRA,the efficiencies of the 8 intervention methods in descending order were modified Zuogui Pills + HRT(SUCRA=97.0),HRT(SUCRA= 77.9),Liuwei Dihuang Pills + HRT(SUCRA=76.6),Kuntai Capsules + HRT(SUCRA=46.5),Nuangong Qiwei Powder+HRT(SUCRA=38.9),Ankun Zhongzi Pills + HRT(SUCRA=29.9),modified Erxian Decoction + HRT(SUCRA=18.1),and Zishen Yutai Pills + HRT(SUCRA=15.1).Conclusion All kinds of Chinese medicines combined with HRT exert stronger effect on improving the primary outcome indicators than HRT alone for the treatment of POF.The intervention with Nuangong Qiwei Powder+HRT exerts the highest probability of the optimal regimen for enhancing the efficiency,and the intervention with Zuogui Pills + HRT exerts the highest probability of the optimal regimen for lowering the serum FSH level.However,due to the low quality of the included studies,more rigorously-designed,large sample-size,and high-quality randomized controlled trials need to be conducted in the future to provide conclusive evidence-based evidence.

Clinical efficacy of anlotinib monotherapy in second-line treatment of extensive stage small cell lung cancer with poor PS score / 国际肿瘤学杂志

Objective:To investigate the clinical efficacy and safety of anlotinib monotherapy in second-line treatment of extensive stage small cell lung cancer (ES-SCLC) with poor performance status (PS) score after treatment failure with first-line standard regimen.Methods:Thirty-three patients with ES-SCLC who failed to receive first-line standard treatment and had poor PS score were selected from Fuyang People's Hospital of Anhui Province from January 2021 to December 2022. All patients were given anrotinib 10 mg orally for second-line treatment, which was taken for 2 weeks and stopped for 1 week, with every 21 days being a cycle period, until the disease progressed or the patient became intolerable. Objective response rate (ORR), disease control rate (DCR) and adverse reactions were observed. Progression-free survival (PFS) was estimated by Kaplan-Meier method, and the influencing factors of PFS were analyzed by Cox regression model.Results:After at least 2 cycles of anlotinib monotherapy, there were no complete remission, 5 cases of partial remission, 17 cases of stable disease, 11 cases of progressive disease. ORR was 15.2% (5/33), DCR was 66.7% (22/33). The median PFS was 3.7 months (95% CI: 2.9-4.5 months). Univariate analysis showed that first-line recurrence time ( χ2=4.90, P=0.027), brain metastases ( χ2=12.42, P<0.001), liver metastases ( χ2=11.05, P=0.001) and controlling nutritional status (CONUT) score ( χ2=12.43, P<0.001) were the influential factors of PFS in ES-SCLC patients with poor PS score and first-line treatment failure of anlotinib monotherapy. Multivariate analysis showed that brain metastases ( HR=3.21, 95% CI: 1.24-8.29, P=0.016), liver metastases ( HR=2.80, 95% CI: 1.03-7.61, P=0.044) and CONUT score ( HR=2.72, 95% CI: 1.16-6.38, P=0.021) were independent influencing factors of PFS in ES-SCLC patients with first-line treatment failure of anlotinib monotherapy and poor PS score. Common adverse reactions were fatigue, hypertension, anorexia, etc. Most of the adverse reactions were grade 1-2, with the incidence of grade 3 adverse reactions being 9.1% (3/33), and no grade 4-5 adverse reactions occurred. Conclusion:The clinical efficacy of anlotinib monotherapy in second-line treatment of ES-SCLC with poor PS score and failure of first-line standard regimen is good, and the adverse reactions are controllable.

Effect of using 131I therapy or not after thyroidectomy in patients with intermediate-risk differentiated thyroid cancer / 中华核医学与分子影像杂志

The main goal of radioactive iodine (RAI) administrated for patients with indeterminate-risk differentiated thyroid cancer (DTC) is removing occult microscopic residual disease after a total thyroidectomy, aiming to reduce recurrence and metastasis, then to improve disease-free survival. This treatment is called as adjuvant therapy, which also ablates the remnant thyroid tissue together. According to the current thyroid cancer management guidelines (2015 American Thyroid Association management guidelines), intermediate-risk patients can be selectively administered RAI. By reviewing articles about DTC patients with indeterminate-risk who underwent RAI or not after thyroidectomy, this article shows that there are inconsistent opinions on 131I decreasing recurrence and improving survival. In addition, apart from unexplained hyperthyroglobulinemia as an indication for 131I therapy, no other uniform clinicalpathological characteristics are recommended.

Time-related association between fluid balance and prognosis in sepsis patients: a cohort study based on MIMIC-IV database / 中华危重病急救医学

OBJECTIVE@#To investigate time-related association between fluid balance and prognosis in sepsis patients.@*METHODS@#A retrospective cohort study was conducted based on the data of sepsis patients in the Medical Information Database for Intensive Care-IV 2.0 (MIMIC-IV 2.0) from 2008 to 2019. Sepsis patients aged ≥ 18 years who were admitted to intensive care unit (ICU) for at least 2 days were included. The daily fluid balance and cumulative fluid balance (CFB) were calculated from days 1 to 7 after ICU admission. According to CFB,the patients were divided into negative fluid balance group (CFB% < 0%), fluid balance group (0% ≤ CFB% ≤ 10%), and fluid overload group (CFB% > 10%). In-hospital mortality was the primary outcome. Multifactorial Logistic regression was used to analyze time-related association between different CFB and the risk of in-hospital mortality in patients with sepsis during 7 days after ICU admission. In addition, subgroup analysis was performed on patients with septic shock and patients with sepsis who stayed in the ICU for 7 days or longer.@*RESULTS@#A total of 11 437 patients with sepsis were included, of which 6 595 were male and 4 842 were female. The mean age was (64.4±16.4) years. A total of 10 253 patients (89.6%) survived and 1 184 patients (10.4%) died during hospitalization. Compared with the survival group, patients in the death group were older, lighter, had higher sequential organ failure assessment (SOFA), simplified acute physiology score II (SAPS II), longer ICU stay, higher incidence of septic shock, and higher proportion of invasive mechanical ventilation, renal replacement therapy (RRT) and vasoactive drugs. In terms of comorbidities, congestive heart failure, renal disease, liver disease, and malignancy were more common in the death group. The death group had a higher daily fluid balance than the survival group during 7 days after ICU admission, the CFB in the two groups gradually increased with length of ICU stay. After adjusting variables such as age, gender, race, SOFA score, SAPS II score, comorbidities, and the use of invasive mechanical ventilation, RRT and vasoactive drugs, multivariate Logistic regression analysis showed that fluid overload on day 1 after ICU admission was a protective factor for the reduced risk of in-hospital mortality in sepsis patients [odds ratio (OR) = 0.74, 95% confidence interval (95%CI) was 0.64-0.86, P = 0.001]. However, fluid overload on day 3 was a risk factor for in-hospital mortality in sepsis patients (OR = 1.70, 95%CI was 1.47-1.97, P < 0.001) and the risk of in-hospital mortality was significantly increased from day 4 to day 7. Furthermore, the same results were obtained in patients with septic shock and sepsis patients who stayed in the ICU for 7 days or longer.@*CONCLUSIONS@#Fluid overload on day 1 was associated with reduced in-hospital mortality. However, from the third day, fluid overload increases the risk of in-hospital mortality. Thus, managing fluid balance at different times may improve prognosis.

FBXO38 regulates ocular melanoma proliferation through the PI3K-Akt signaling pathway / 上海交通大学学报（医学版）

Objective·To investigate the effect of F-box only protein 38(FBXO38)on the ocular melanoma proliferation and the potential regulatory pathway.Methods·Human skin cutaneous melanoma A375 and human uveal melanoma OMM2.3 cell lines with FBXO38 knockdown and overexpression were constructed by FBXO38 short hairpin RNA(shRNA)and FBXO38 overexpression plasmids respectively.Knockdown and overexpression efficiency of FBXO38 at transcription and protein levels were verified by using quantitative real-time PCR(qRT-PCR)and Western blotting.The effects of FBXO38 on melanoma cell proliferation were detected through clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay.By using The Cancer Genome Atlas(TCGA)database,differentially expressed genes were analyzed in the high and low expression groups of FBXO38.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment was performed to reveal the signaling pathways associated with FBXO38.CCK8 cell proliferation assay was used to detect the inhibition rates of the signaling pathway inhibitors on cells with different FBXO38 expression levels.qRT-PCR and Western blotting were used to detect whether the signaling pathway was activated after knocking down FBXO38.Results·qRT-PCR and Western blotting verified that mRNA and protein expression levels of FBXO38 in FBXO38 knockdown A375 and OMM2.3 cell lines decreased compared with the control group,while the expression levels of FBXO38 in the overexpression cell lines increased compared with wild type group(P＜0.05).Clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay showed that FBXO38 knockdown significantly enhanced the proliferation of A375 and OMM2.3 cells(P＜0.05),while overexpression of FBXO38 inhibited melanoma cell proliferation(P＜0.05).Enrichment analysis showed that in skin cutaneous melanoma and uveal melanoma,FBXO38 expression influenced the phosphoinositide 3-kinase/protein kinase B(PI3K-Akt)pathway activation.Compared with those in the control group,the inhibition rates of P13K inhibitor LY294002 and mTOR1 inhibitor Everolimus in the FBXO38 knockdown group significantly improved(P＜0.05),while their inhibition rates of the overexpression group significantly decreased compared with those of control cells(P＜0.05).Western blotting results showed that after knocking down FBXO38,expression levels of PTEN,P21 and P53 proteins decreased,while expression level of MDM2 protein increased.The qRT-PCR results showed a significant decrease in P53 transcription level(P＜0.05)and a significant increase in MDM2 transcription level in FBXO38 knockdown cells(P＜0.05).Conclusion·FBXO38 plays a role in regulating the proliferation of ocular melanoma,and this regulatory effect is related to the PI3K-Akt signaling pathway.

Value of a risk assessment model in predicting venous thromboembolism in patients with liver failure after artificial liver support therapy / 临床肝胆病杂志

Objective To investigate the value of a risk assessment model in predicting venous thromboembolism (VTE) in patients with liver failure after artificial liver support therapy. Methods A retrospective analysis was performed for the clinical data of 124 patients with liver failure who received artificial liver support therapy in Affiliated Drum Tower Hospital of Nanjing University Medical School from March 2019 to December 2021, among whom there were 41 patients with VTE (observation group) and 143 patients without VTE (control group). Related clinical data were compared between the two groups, and the Caprini risk assessment model was used for scoring and risk classification of the patients in both groups. The t -test was used for comparison of continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; the Mann-Whitney U rank sum test was used for comparison of ranked data between two groups. The logistic regression analysis was used to investigate the independent risk factors for VTE in patients with liver failure after artificial liver support therapy. The receiver operating characteristic (ROC) curve was used to investigate the value of Caprini score and the multivariate predictive model used alone or in combination in predicting VTE. Results The observation group had a significantly higher Caprini score than the control group (4.39±1.10 vs 3.12±1.04, t =6.805, P < 0.001). There was a significant difference between the two groups in risk classification based on Caprini scale ( P < 0.05), and the patients with high risk or extremely high risk accounted for a higher proportion among the patients with VTE. The univariate analysis showed that there were significant differences between the two groups in age ( t =6.400, P < 0.001), catheterization method ( χ 2 =14.413, P < 0.001), number of times of artificial liver support therapy ( Z =-4.720, P < 0.001), activity ( Z =-6.282, P < 0.001), infection ( χ 2 =33.071, P < 0.001), D-dimer ( t =8.746, P < 0.001), 28-day mortality rate ( χ 2 =5.524, P =0.022). The multivariate analysis showed that number of times of artificial liver support therapy (X 1 ) (odds ratio [ OR ]=0.251, 95% confidence interval [ CI ]: 0.111-0.566, P =0.001), activity (X 2 ) ( OR =0.122, 95% CI : 0.056-0.264, P < 0.001), D-dimer (X 3 ) ( OR =2.921, 95% CI : 1.114-7.662, P =0.029) were independent risk factors for VTE in patients with liver failure after artificial liver support therapy. The equation for individual predicted probability was P =1/[1+e -(7.425-1.384X 1 -2.103X 2 +1.072X 3 ) ]. The ROC curve analysis showed that Caprini score had an area under the ROC curve of 0.802 (95% CI : 0.721-0.882, P < 0.001), and the multivariate model had an area under the ROC curve of 0.768 (95% CI : 0.685-0.851, P < 0.001), while the combination of Caprini score and the multivariate model had an area under the ROC curve of 0.957 (95% CI : 0.930-0.984, P < 0.001). Conclusion The Caprini risk assessment model has a high predictive efficiency for the risk of VTE in patients with liver failure after artificial liver support therapy, and its combination with the multivariate predictive model can significantly improve the prediction of VTE.

Clinical effect of acupuncture based on syndrome differentiation in the treatment of chronic insomnia and its influence on cognitive function / 中国针灸

OBJECTIVE@#To compare the effect of acupuncture based on syndrome differentiation and estazolam in the treatment of chronic insomnia and its influence on cognitive function.@*METHODS@#A total of 90 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 45 cases in each group. The acupuncture group was treated with acupuncture at Sishencong (EX-HN 1) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6) combined with compatibility of acupoints based on syndrome differentiation, once a day for 6 d and then rest for 1 d, for a total of 4 weeks. The medication group was treated with oral estazolam tablets before bedtime, 1 tablet each time, for a total of 4 weeks. Before and after treatment, the scores of Pittsburgh sleep quality index (PSQI), mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and auditory verbal memory test (AVMT) of the two groups were compared, and the effects were evaluated.@*RESULTS@#After treatment, the PSQI sub-item scores and total scores of the two groups were lower than those before treatment ( P<0.05 ), and above scores in the acupuncture group were lower than those in the medication group ( P<0.05 ); the scores of MMSE, MoCA and AVMT in the two groups were higher than those before treatment ( P<0.05 ), and the scores in the acupuncture group were higher than those in the medication group ( P<0.05 ). The total effective rate of the acupuncture group was 80.0% (36/45), which was higher than 53.3% (24/45) in the medication group (P<0.05).@*CONCLUSION@#Syndrome differentiation acupuncture can improve the sleep quality and cognitive function of patients with chronic insomnia, and the curative effect is better than that of estazolam.

Exploring the treatment of sepsis-associated acute lung injury with Liangge Powder via ERK1/2 and PI3K/AKT pathways: based on network pharmacology and whole animal experimentation / 中华劳动卫生职业病杂志

Objective: To investigate the therapeutic effect and mechanism of Liangge Powder against sepsis-induced acute lung injury (ALI) . Methods: From April to December 2021, the key components of Liangge Powder and its targets against sepsis-induced ALI were analyzed by network pharmacology, and to enrich for relevant signaling pathways. A total of 90 male Sprague-Dawley rats were randomly assigned to sham-operated group, sepsis-induced ALI model group (model group), Liangge Powder low, medium and high dose group, ten rats in the sham-operated group and 20 rats in each of the remaining four groups. Sepsis-induced ALI model was established by cecal ligation and puncture. Sham-operated group: gavage with 2 ml saline and no surgical treatment. Model group: surgery was performed and 2 ml saline was gavaged. Liangge Powder low, medium and high dose groups: surgery and gavage of Liangge Powder 3.9, 7.8 and 15.6 g/kg, respectively. To measure the wet/dry mass ratio of rats lung tissue and evaluate the permeability of alveolar capillary barrier. Lung tissue were stained with hematoxylin and eosin for histomorphological analysis. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6 and IL-1β in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The relative protein expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-protein kinase B (AKT), and p-ertracellular regulated protein kinases (ERK) were detected via Western blot analysis. Results: Network pharmacology analysis indicated that 177 active compounds of Liangge Powder were selected. A total of 88 potential targets of Liangge Powder on sepsis-induced ALI were identified. 354 GO terms of Liangge Powder on sepsis-induced ALI and 108 pathways were identified using GO and KEGG analysis. PI3K/AKT signaling pathway was recognized to play an important role for Liangge Powder against sepsis-induced ALI. Compared with the sham-operated group, the lung tissue wet/dry weight ratio of rats in the model group (6.35±0.95) was increased (P<0.001). HE staining showed the destruction of normal structure of lung tissue. The levels of IL-6 [ (392.36±66.83) pg/ml], IL-1β [ (137.11±26.83) pg/ml] and TNF-α [ (238.34±59.36) pg/ml] were increased in the BALF (P<0.001, =0.001, <0.001), and the expression levels of p-PI3K, p-AKT and p-ERK1/2 proteins (1.04±0.15, 0.51±0.04, 2.31±0.41) were increased in lung tissue (P=0.002, 0.003, 0.005). The lung histopathological changes were reduced in each dose group of Liangge Powder compared with the model group. Compared with the model group, the wet/dry weight ratio of lung tissue (4.29±1.26) was reduced in the Liangge Powder medium dose group (P=0.019). TNF-α level [ (147.85±39.05) pg/ml] was reduced (P=0.022), and the relative protein expression levels of p-PI3K (0.37±0.18) and p-ERK1/2 (1.36±0.07) were reduced (P=0.008, 0.017). The wet/dry weight ratio of lung tissue (4.16±0.66) was reduced in the high-dose group (P=0.003). Levels of IL-6, IL-1β and TNF-α[ (187.98±53.28) pg/ml, (92.45±25.39) pg/ml, (129.77±55.94) pg/ml] were reduced (P=0.001, 0.027, 0.018), and relative protein expression levels of p-PI3K, p-AKT and p-ERK1/2 (0.65±0.05, 0.31±0.08, 1.30±0.12) were reduced (P=0.013, 0.018, 0.015) . Conclusion: Liangge Powder has therapeutic effects in rats with sepsis-induced ALI, and the mechanism may be related to the inhibition of ERK1/2 and PI3K/AKT pathway activation in lung tissue.