Objective To investigate the application of intraoperative neuromonitoring (IONM) during thyroidectomy for non-recurrent laryngeal nerve (NRLN).Methods From Oct.2013 to Apr.2016,2846 patients underwent thyroidectomy with the application of IONM,and 11 patients with non-recurrent laryngeal nerve were analyzed.Results 11 cases of NRLN were all accurately identified by IONM,and no injury of NRLN occurred during thyroid surgery.Conclusions NRLN is uncommon in clinical and it is difficult to be predicted before surgery and easy to be injured.The application of IONM can reduce the possibility of NRLN injury remarkably.

Objective Study and analyze the benefits and risks of unilateral thyroidectomy for 1 to 4 cm thyroid cancer in primary surgery.Methods The patients who underwent thyroidectomy for 1 to 4 centimeters WDTC (May 2014 to June 2015) were retrospectively reviewed,and the patients with preoperatively known high-risk characteristics were excluded.One hundred and seventy-one patients would have been eligible for lobectomy as the initial operation based on current American Thyroid Association guidelines.The proportion of patients who need secondary surgery was estimated basing on pathological characteristics.Result In this group,49％ patients would have to undergo a secondary surgery if they took lobectomy as the initial operation.Conclusions Patients with 1 to 4 centimeters WDTC who accept unilateral thyroidectomy may take the risk of secondary surgery.Surgeons and patients need to balance the relative benefits and risks of initial TT versus lobectomy before the operation.

Objective To analyze the clinical features and laboratory data of 10 patients with macrophage activation syndrome (MAS) complicating systemic onset juvenile idiopathic arthritis (soJIA),which were characterized by acute severe liver injury.Methods Data of 10 patients with soJIA/MAS from Nanjing Children's Hospital were collected retrospectively.The clinical features,laboratory findings,treatment,outcomes and prognosis were analyzed.Results In the total 10 patients,female (6/10) outnumbered male.Their age ranged from 1.5 to 9.5 years old (average 5.2±2.6).The most remarkable clinical manifestations were severe liver injury without systemic features,representing as hepatomegaly (10/10),splenomegaly (2/10) and strikingly increased transaminase (10/10,median:ALT 1 445 U/L,AST 885 U/L).Central nervous system dysfunction and hemorrhages were recorded in 20％ of the patients.Two patients had pulmonary infection.Laboratory data showed that platelet count was less than normal or precaution value (10/10,≤262×10g/L).Hyperferritinaemia (10/10,median:17 329 mg/ml) and soluble CD25 elevation (median:3 140 U/ml) were common in the soJIA/MAS patients.Evidence of macrophage hemophagocytosis was found in 90％ of the patients (9/10) who underwent bone marrow aspiration.Pathological findings of liver biopsy from 1 patient revealed massive infiltration of mononuclear cells in the portal tracts.Nearly all patients (9/10) received intravenous pulse methylprednisolone therapy,combined with cyclosporine A and high-dose intravenous immunoglobulin.Eight patients had good outcome.Only 2 patients were complicated with severe interstitial lung disease during 12-months follow-up.Conclusion MAS should be considered when patients with soJIA represents acute severeliver injury without systemic features combined with other laboratory data.Intravenous pulse methylprednisolone and cyclosporine A therapy may improve the prognosis of soJIA/MAS.

Objective To investigate the changes of miR-146a expression in serum,hippocam-pus and prefrontal cortex in postoperative cognitive dysfunction (POCD) mice.Methods Fifty healthy male C57BL/6 mice,aged 12-14 weeks,weighing 25-30 g,were randomly divided into two groups (n =25 each)using a random number table:control group (group C)and anesthesia plus sur-gery group (group AS).Mice in group AS underwent open tibial fracture of the left hind paw with in-tramedullary fixation in aseptic conditions under general anesthesia with 2.1% isoflurne.Ten mice in each group received the fear conditioning test (FCT)on the 1,3 and 7 days after anesthesia/surgery. The rest of mice were sacrificed 24 h before (baseline),and 6,12,24,48 h after anesthesia/surgery, and then the serum,prefrontal cortex and hippocampus were collected or removed for detection of the expression of miR-146a using quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results Compared with group C,the percentage of freezing time in contextual FCT was sig-nificantly decreased (P <0.05)in group AS,while no significant change in freezing time percentage was found in tone-cued FCT.In serum,compared with group C,miR-146a expression at 6,12,24, 48 h after anesthesia/surgery was significantly up-regulated in group AS (P < 0.05 );and in group AS,the expression of miR-146a was significantly decreased 6,24,48 h as compared to that at 12 h after anesthesia/surgery (P <0.05).In hippocampus,compared with group C,miR-146a expression at 6,12,24,48 h after surgery was significantly up-regulated in group AS (P <0.05);and in group AS,the expression of miR-146a at 6,48 h after surgery was significantly decreased as compared to that at 12 h after anesthesia/surgery (P <0.05).In prefrontal cortex,compared with group C,miR-146a expression at 24,48 h after surgery was significantly up-regulated in group AS (P <0.05);and in group AS,the expression of miR-146a was significantly increased at 48 h as compared to that at 24 h after anesthesia/surgery (P <0.05).Conclusion The expression of miR-146a in serum,hippocam-pus and prefrontal cortex in POCD mice was up-regulated,and changes of miR-146a expression may be related to the development of POCD.

Objective To investigate the effectiveness of three different anesthetic techniques in intraventricular catheterization and its effect on the survival rate of rats. Methods Thirty Wistar rats were equally allocated into 3 groups:chloral hydrate group,pentobarbital sodium group and isoflurane group. Intraventricular catheterization was performed in the rats after anesthesia with i. p. injection of chloral hydrate and pentobarbital sodium, and isoflurane inhalation, respectively. Levels of blood glucose were detected before and at 15 and 30 minutes and 1, 3, 7, 14, 28 days after anesthesia. Body mass and 24-hour food intake were recorded before and at 1, 3, 7 days after anesthesia. The onset time and effective time of anesthesia, operation time and the survival rates on 30 days of the rats were compared and analyzed. Results The onset time and effective time of anesthesia, and the operation time in the isoflurane group were shorter than that in the chloral hydrate group, while these parameters in this group were shorter than that in the pentobarbital sodium group. Blood glucose in the chloral hydrate group was apparently increased during the surgical operation, while the body mass, 24-hour food intake and blood glucose were decreasing since one day after operation, and all the rats in this group died during the 30-day observation, mainly, due to enteroplegia. Blood glucose in the pentobarbital sodium group was mildly increased after anesthesia, while the body mass, 24-hour food intake and blood glucose were mildly decreased at one day after operation and recovered within one week. In this group, 3 rats died of respiratory distress due to overdose anesthesia and one rat died during the 30 day-observation. The blood glucose in the isoflurane group was mildly increased after operation, while the 24-hour food intake and blood glucose did not markedly changed, the body mass was stably increased, and no rat died during the 30-day-observation. Conclusions Intraperitoneal injection of chloral hydrate is not suitable for intraventricular catheterization in rats. Intraperitoneal injection of pentobarbital sodium can be only carefully applied for intraventricular catheterization under poorly-limited conditions. Isoflurane inhalation anesthesia is recommended for intraventricular catheterization in rats.

OBJECTIVE Based on fibroblast activation protein(FAP)gene promoter as the response element,to develop a new dual luciferase reporting system for the screening of drugs related to myocardial fibrosis.METHODS The promoter fragment of mouse FAP gene was synthesized in vitro and cloned into plasmid psiCHECK2 to replace HSV-TK promoter,and then a new recombinant plasmid psiCHECK2-FAP was obtained.After the recombinant plasmid psiCHECK2-FAP was digested by restriction endonucliase Hind Ⅲ,the product digested was identified by agar-gel electrophoresis and sequencing.After psiCHECK2-FAP was transient transfected into mouse cardiac fibroblasts(MCFs),and continued cultured for 24 h,and MCFs were treated with Ransforming growth factor β1(TGF-β1,5 μg·L-1)or angiotensinⅡ(Ang Ⅱ,1 μmol·L-1)or palmitic acid(PA,100 μmol·L-1)for 0,12,24,48 h,respectively,the double luciferase reporter gene assay was used to detect luciferase activity;After psiCHECK2-FAP was transient transfected into MCFs,the cells were pretreated with Dapa(1 μmol·L-1)for 1 h,and supplemented with TGF-β1(5 μg·L-1)or AngⅡ(1 μmol·L-1)or PA(100 μmol·L-1),continued treatment for 24 h,the double luciferase reporter gene assay was used to detect luciferase activity,and the expression of collagenⅠand collagen Ⅲ protein was detected with Western blotting.RESULTS The recombinant plasmid psiCHECK2-FAP was digested into two fragments by Hind Ⅲ with the expected strip size,and the sequencing results were completely consistent with the theoretical sequence;Compared with control group,the collagenⅠand collagen Ⅲ protein expression were significantly increased by TGF-β1 or Ang Ⅱ or PA in MCFs(P<0.05,P<0.01).However,compared with TGF-β1 or Ang Ⅱ or PA group,the intervention of Dapa significantly alleviated the promoter activity of FAP gene and the expression of collagenⅠand collagen Ⅲ protein(P<0.05,P<0.01);Compared with control group,luciferase activity was significantly increased by TGF-β1 or Ang Ⅱ or PA(P<0.05,P<0.01),reaching the peak at 24 h.Compared with TGF-β1 or AngⅡ or PA group,the intervention of Dapa significantly decreased luciferase activity(P<0.05,P<0.01).CONCLUSSION Based on the promoter of FAP gene as the response element,a noval dual luciferase reporter gene system was established and showed a good sensitivity to the promyocardial fibrosis factor in MCFs,which can provide strategies for the development of antimyocar-dial fibrosis drugs.

Objective To assess the alterations of negative functional connectivity(FC),its relationship with clinical symptoms,and its potential value in schizophrenia(SZ).Methods Resting-state functional magnetic resonance imaging(rs-fMRI)data were acquired from patients with SZ and healthy controls(HC).For each participant,the whole brain image was first divided into 272 regions and then the FC between each pair of these regions was calculated using Pearson's correlation coefficient.Group-level negative FCs were identified using permutation test for each group.Each of the identified negative FCs was then compared between patients and controls to identify the altered negative FCs.Then,Spearman rank correlation was adopted to examine the relationship between the altered negative FCs and clinical variables.Finally,to evaluate the diagnostic value of negative FC in SZ,a multivariate pattern analysis(MVPA)was performed to distinguish between SZ and HC based on negative FCs.Results Ninety-one patients with SZ and 91 HC were included in this study,and 207 negative FCs in total were identified.Among the identified 207 negative FCs,12(constituting 5.80％of the total 207 negative FCs)were significantly altered in SZ compared with HC(Bonferroni correction,P<0.05),of which 11 were significantly decreased(i.e.,closer to 0)in SZ.The correlation analyses identified 2 significant associations-one was between a negative FC and the total score of the psychotic symptoms rating scales-auditory hallucinations(r=-0.24,P=0.02)and the other was between a negative FC and the weighted total score of the scale for the assessment of thought,language,and communication(r=0.26,P=0.01).Furthermore,the model for distinguishing between SZ and HC based on negative FCs achieved a classification accuracy of 72.6％that was significantly higher than chance-level accuracy(permutation test,P<0.001).Conclusion Negative FCs are altered in patients with SZ.Given that negative FCs are associated with clinical symptoms,thus they may serve as an imaging biomarker for assisting the diagnosis of SZ.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.