IKBKG is the essential modulator for nuclear factor-κB(NF-κB) signaling pathway, and mutations within this gene can lead to anhidrotic ectodermal dysplasia and immunodeficiency (EDA-ID). Here we report a male patient, who presented with mild frontal bossing, sparse hair, skin pigmentation, conical teeth, and recurrent infections involving bacteria, fungi, and viruses after one month of age, together with hypogammaglobulinemia. These symptoms were consistent with the phenotype of EDA-ID. Genetic analysis revealed a hemizygous mutation c.1249T > G (p.Cys417Gly) in exon 10 of the IKBKG gene in the patient. The mother of the patient was identified as heterozygous carriers of the same mutation. Immunological assessment revealed a significant reduction in memory B cells. The patient showed no skewed TCR diversity. PHA-induced T-cell proliferation was impaired. IFN-γ secretion by Th cells was significantly reduced after PHA stimulation. IκBα degradation rate retained the same in the patient. We summarized the clinical features of the patient and conducted immunological analysis, in order to increase pediatricians′awareness of this rare disease. For boys with early-onset recurrent infections together with ectodermal dysplasia, IKBKG mutation should be considered. In addition, genetic analysis is needed to exclude pseudogene interference and functional evaluations are required.

Mild cognitive impairment(MCI)is often regarded as a prodromal stage of dementia,primarily characterized by mild decline in cognitive function.Due to the mild nature of its symptoms,many MCI cases miss the opportunity for intervention.Research indicates that linguistic changes in MCI may precede other cognitive symptoms,providing an opportunity for early identification and intervention.These linguistic changes include abnormalities in speech rate,pronunciation,and intonation.Speech repetition tasks,such as the five-word test,delayed digit matching,and sentence repetition tests,are effective methods for assessing the speech characteristics of MCI patients.These tasks involve asking patients to repeat specific content,and analyzing the accuracy of their repetitions to assess their speech function.The application of machine learning and deep learning techniques enables automatic extraction of MCI-related features from speech data,improving diagnostic accuracy.The combined application of these techniques contributes to the early detection of MCI,providing a basis for timely intervention.

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Objective:To investigate the diagnostic value of prognostic nutritional index (PNI) and C-reactive protein to albumin ratio(CAR) in Crohn′s disease complicated with intra-abdominal infection (CD-IAI).Methods:From January 2016 to December 2021, the clinical data of 61 patients with Crohn′s disease (CD) and 61 patients with CD-IAI diagnosed at Nanfang Hospital, Southern Medical University were retrospectively analyzed. Crohn′s disease activity index (CDAI), Crohn′s disease endoscopic index of severity (CDEIS), laboratory parameters(white blood cell count, neutrophil ratio, platelet count, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, prothrombin time (PT), fibrinogen, activated partial thromboplastin time (APTT)), PNI and CAR were compared between CD patients and CD-IAI patients. From January to May in 2022 another 30 patients with CD and 13 patients with CD-IAI diagnosed at Nanfang Hospital, Southern Medical University were selected to verify the accuracy of PNI and CAR in predicting CD-IAI. The optimal cut-off values of PNI and CAR in predicting CD-IAI, area under the curve (AUC), Youden index, sensitivity and specificity were calculated by receiver operating characteristic curve (ROC). Spearman correlation was used to analyze the correlation between PNI, CAR, CDAI, and CDEIS, and logistic regression was performed to analyze the influencing factors of CD-IAI. Independent sample t test and Mann-Whitney U test were used for statistical analysis. Results:CDAI and CDEIS were higher in CD-IAI patients than those of CD patients(256.68±8.50 vs.144.87±7.83; 3.80 (1.80, 5.40) vs. 1.20 (0.20, 2.80)), and the differences were statistically significant( t=-9.67, Z=-4.02, both P<0.001). The white blood cell count, neutrophil ratio, platelet count, CRP, PCT, D-dimer, PT, fibrinogen, and APTT of CD-IAI patients were all higher than those of CD patients (7.81×10 9/L (5.98×10 9/L, 11.39×10 9/L) vs. 5.94×10 9/L (4.86×10 9/L, 7.11×10 9/L); (73.43±10.67)% vs. (62.30±11.03)%; 360.00×10 9/L (266.50×10 9/L, 456.00×10 9/L) vs. 294.00×10 9/L (222.50×10 9/L, 356.00×10 9/L); 44.27 mg/L (16.82 mg/L, 82.65 mg/L) vs. 3.42 mg/L (0.59 mg/L, 18.33 mg/L); 0.07 μg/L (0.04 μg/L, 0.22 μg/L) vs. 0.04 μg/L (0.02 μg/L, 0.05 μg/L); 0.75 mg/L (0.32 mg/L, 2.00 mg/L) vs. 0.26 mg/L (0.15 mg/L, 0.46 mg/L); 11.90 s (11.40 s, 12.90 s) vs. 11.20 s (10.45 s, 11.70 s); 4.58 g/L (3.59 g/L, 5.59 g/L) vs. 2.99 g/L (2.17 g/L, 4.23 g/L); 30.40 s (28.30 s, 32.80 s) vs. 28.00 s (25.45 s, 31.10 s)), and the differences were statistically significant ( Z=-4.48; t=-5.66; Z=-2.71, -6.47, -3.78, -4.87, -4.87, -5.44 and -2.74; all P<0.01). The serum albumin level of CD-IAI patients was lower than that of CD patients (34.10 g/L (31.40 g/L, 36.90 g/L) vs. 39.00 g/L (35.10 g/L, 43.20 g/L)), and the difference was statistically significant( Z=-3.91, P<0.001). The PNI of CD-IAI patients was lower than that of CD patients (41.65, (38.58, 44.58) vs. 47.80 (40.45, 52.98)), while CAR was higher than that of CD patients (1.29 (0.48, 2.67) vs. 0.10 (0.01, 0.46)), and the differences were statistically significant ( Z=-3.83 and -6.44, both P<0.001). The results of Spearman correlation analysis showed that PNI was negatively correlated with CAR, CDAI, and CDEIS ( r=-0.64, -0.53 and -0.50, all P<0.001), and CAR was positively correlated with CDAI and CDEIS ( r=0.63 and 0.52, both P<0.001). The results of logistic regression analysis showed that high level of PNI was a protective factor for CD-IAI ( OR= 0.911, 95% confidence interval 0.864 to 0.961), and high level of CAR was a risk factor for CD-IAI ( OR=2.846, 95% confidence interval 1.745 to 4.644). The results of ROC indicated that the AUC value of combined PNI and CAR in the diagnosis of CD-IAI was 0.829 ( P<0.001), Youden index was 0.541, the sensitivity was 0.934, and the specificity was 0.607. The sensitivity and specificity of optimal cut-off value of the combination of PNI and CAR in predicting CD-IAI were 0.692 and 0.967. Conclusions:PNI and CAR have certain diagnostic value in CD-IAI. The risk of CD-IAI is high when PNI <45.550 and CAR >0.466.

Objective:To evaluate the effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice and its relationship with adenosine monophosphate-activated protein kinase(AMPK)/ signal transducer and activator of transcription 6(STAT6) pathway.Methods:Twenty-five 8-week-old male C57BL/6N mice were divided into control group, steatotic liver group, berberine treatment group(200 mg·kg -1·d -1), AMPK inhibitor Compound C treatment group(0.2 mg·kg -1·d -1), and STAT6 inhibitor AS1517499 treatment group(10 mg·kg -1·d -1). After 12 weeks of intervention, the mice and liver tissue were weighed, and serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) as well as liver malondialdehyde and superoxide dismutase were measured; liver tissue HE, Masson, and oil red O staining were performed. Western blotting was used to detect the expressions of necroptosis related proteins[receptor interaction protein kinase 3(RIPK3), phosphorylated(p-) mixed lineage kinase domain-like(MLKL)], AMPK, p-AMPK, and p-STAT6. Results:Compared with control group, the steatotic liver group had higher quality of liver and liver index, and higher levels of serum AST, ALT, triglyceride, TNF-α, IL-1β, and oxidative stress( P<0.05); Liver tissue was full of cavity changes and inflammatory cell infiltration, widely distributed red lipid droplets and obvious blue fiber dyeing; The expressions of RIPK3 and p-MLKL were up-regulated ( P<0.05), but the levels of p-AMPK and p-STAT6 were relatively reduced ( P<0.05). Compared with the steatotic liver group, berberine intervention decreased liver quality and liver index, improved liver function, reduced blood lipid levels, pro-inflammatory factor expression and oxidative stress level, and significantly alleviated the degree of liver steatosis and fibrosis, the levels of RIPK3 and p-MLKL ( P<0.05), while the expressions of p-AMPK and p-STAT6 were increased significantly ( P<0.05). As compared with the berberine treatment, AMPK and STAT6 inhibitor treatment could offset the protective effect of berberine on steatotic liver, moreover, the expressions of RIPK3 and p-MLKL were increased ( P<0.05). There was no statistical difference in AMPK total protein content among the five groups ( P>0.05). Conclusion:Berberine can activate AMPK/STAT6 pathway to inhibit the necroptosis of hepatocyte, thus plays a protective role on non-alcoholic fatty liver disease in mice.

Objective:To evaluate the reliability and validity of the Chinese version of the continuity assessment record and evaluation(CARE)among the elderly in nursing institutions.Methods:A total of 269 elders in nursing institutions were face-to-face interviewed.Information was collected with the Chinese version of CARE, the mini mental state examination(MMSE), the geriatric depression scale(GDS), the visual analogue pain score(VAS), the barthel index(BI), the lawton instrumental activities of daily living scale(IADL), and the euroqol five dimensions questionnaire(EQ-5D). A week later, 30 of the elderly were re-evaluated with the Chinese version of CARE.Data were analyzed for reliability and validity.Results:For both the total score and the score for each dimension of CARE, the interrater reliability and test-retest reliability expressed by the intraclass correlation coefficient(ICC)ranged from 0.945 to 1.000 and 0.842 to 1.000, respectively; the internal consistency expressed by Cronbach's α ranged from 0.717 to 1.000, all reaching good levels of reliability.The criterion-related validity of the relevant dimensions of CARE showed high correlations with MMSE, GDS, VAS, BI, IADL and EQ-5D(0.918, 0.802, 0.998, 0.931, 0.924 and 0.917, respectively)(all P=0.000). Conclusions:The Chinese version of CARE has good reliability and validity among elders in nursing institutions, and can be used as a comprehensive assessment tool for the elderly in nursing institutions in China.

Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.

Objective:To explore the effective ability and strategy of improving in-hospital emergency in large general hospitals through investigating and analyzing the epidemiological characteristics and outcomes of patients treated by rapid response team (RRT) in the Fourth People's Hospital of Shenyang.Methods:The clinical data of 145 patients treated by RRT in the Fourth People's Hospital of Shenyang from April 1st to June 30th in 2019 were retrospectively analyzed. The clinical data including gender, age, RRT response time, disease type, direct cause of RRT initiation, the incidence of cardiac arrest, intensive care unit (ICU) admission rate and outcome were statistically analyzed. The correlation between indicators was analyzed by Pearson correlation. Pareto diagram was used to analyze the direct cause of RRT initiation.Results:A total of 145 patients were treated by RRT within 3 months. The ratio of male ( n = 85) to female ( n = 60) was 1.42∶1. The age of patients treated by RRT was (72.83±14.84) years old, and the response time was (3.27±1.42) minutes. The incidence of cardiac arrest was 23.4% (34/145), and the ICU admission rate was 29.7% (43/145). The hospital mortality was 40.0% (58/145), and the rescue success rate was 60.0% (87/145). Correlation analysis showed that there was a significant positive correlation between the incidence of cardiac arrest and hospital mortality ( r = 0.545, P < 0.01). According to the disease type of patients treated by RRT analysis, respiratory system diseases ( n = 44, 30.3%) accounted for the most, followed by circulatory system diseases ( n = 43, 29.7%), nervous system diseases ( n = 25, 17.2%), digestive system diseases ( n = 19, 13.1%), trauma ( n = 5, 3.4%), endocrine system diseases ( n = 3, 2.1%), urinary system diseases ( n = 2, 1.4%) and others ( n = 4, 2.8%). Further analysis showed that patients aged between 85 years old and 94 years old were prone to the respiratory system diseases, accounting for 48.5% (16/33) of the population in this age group, while the cardiovascular system diseases were the most common in patients older than 55 years old, accounting for 31.0% (40/129) of the population in this age group. Pareto diagram showed that the percentages of direct causes of RRT initiation ranked from high to low, the cumulative percentage of pneumonia ( n = 30, 20.7%), acute myocardial infarction ( n = 26, 17.9%), stroke ( n = 20, 13.8%), septic shock ( n = 14, 9.7%), heart failure ( n = 10, 6.9%), respiratory and cardiac arrest ( n = 9, 6.2%), and gastrointestinal bleeding ( n = 7, 4.8%), which were the main direct causes of RRT initiation with a total of 80%. Conclusions:Respiratory system and circulatory system diseases are the main causes for RRT treatment in first-aid patients in the Fourth People's Hospital of Shenyang. The hospital mortality significantly increases once patients suffered cardiac arrest. The RRT can provide effective intervention earlier and faster, and establish a complete RRT emergency strategy, which is helpful to improve the in-hospital emergency ability in large general hospitals.

Objective: To evaluate the safety of population based sequential vaccination schedule of inactivated poliovirus vaccines prepared with different strains. Methods: This randomized, parallel-group controlled trial was conducted from March, 2017 to May, 2018, in Shanghai. Adverse reaction data of Sabin strain inactivated polio vaccine (sIPV), wild strains inactivated polio vaccines (wIPV) and bivalent types Ⅰ and Ⅲ oral poliomyelitis vaccine (bOPV) were systematically collected through active observation in 1 917 infants in Shanghai after the vaccination at 2, 3, 4 months old. The eligible infants aged 2 months were divided into 4 groups: ①sIPV+sIPV+bOPV group; ②sIPV+wIPV+bOPV group; ③wIPV+sIPV+bOPV group; ④wIPV+wIPV+bOPV group. Results: The incidence of adverse reaction 30 days later after 3 basic dose vaccinations was 16.79% (946/5 633). No serious adverse reaction was reported. Local and systemic reactions were mainly mild. Common local reactions were pain, erythema, cutaneous nodule, etc.; and common systemic reactions were abnormal crying, drowsiness, diarrhea and appetite lost, etc.. The incidence of local reactions 30 days later after 3 basic dose vaccinations was 1.65% (93/5 633), and the incidence rates of grade 1-3 reactions were1.26% (71/5 633), 0.21% (12/5 633) and 0.20% (11/5 633) respectively. The incidence rate of systemic reactions 30 days later after 3 basic vaccinations was 15.14% (853/5 633), and the incidence rates of grade 1-3 reactions were 11.33% (638/5 633), 3.18% (179/5 633) and 0.64% (36/5 633) respectively. There were no significant differences in the rate of grade 3 reaction among different groups (χ²=4.17, P=0.24). Conclusions No severe adverse reactions related to sequential vaccination of different strain inactivated polio vaccines were observed, most of reactions were mild and all of them were cured. It is safe to use sIPV and wIPV simultaneously or alternately for childhood sequential vaccination.

Objective? To explore the application of three-way connection in air bag pressure monitoring in patients with artificial airway. Methods? Totally 85 patients who received artificial airway formechanical ventilation in the 4th People＇s Hospital of Shenyang from August 2016 to July 2017 were selected and randomized into two groups in whichminimum hermetically sealed pressure (MOP) was used in the air bag to seal the airway. The artificial airway balloon for the observation group (n=43) was connected to a balloon pressure meter by three-way connection to monitor the pressure in the balloon, while the artificial airway balloon for the observation group (n=42) was connected to a balloon pressure meter by direct connection to monitor the pressure in the balloon. The changes of balloon pressure (△P=MOP-monitoring pressure) at 4, 8, 24 and 48 h post air inflation were monitored in both groups. The incidence of regurgitation and aspiration, airway mucosal injury and pulmonary infection were observed in the two groups. Results? There was no statistically significant difference in △P between the two groups at 4 h post air inflation[△P 4 h: (3.76±1.47) vs. (3.82±1.36) cmH2O; (P＞0.05)]. The△P 8, 24 and 48 h of the observation group were lower than those of the control group, and there was statistically significant difference between the two groups [△P 8 h: (5.76±2.58) vs. (7.29±2.42) cmH2O; △P 24 h: (6.32±3.08) vs. (9.38±3.32) cmH2O; △P 48 h: (8.79±5.26) vs. (15.32±5.87) cmH2O; (P＜0.01)]. The incidence rate of regurgitation and aspiration in the observation group was 9.3%, lower than that in the control group, which was 11.9%, and there was statistically significant difference between the two groups (P＜0.05); there was no statistically significant difference in the incidence rate of airway mucosal injury and pulmonary infection between the two groups (P＞ 0.05). Conclusions? The use of three-way connection can reduce air leakage of the artificial airway balloon and reduce the incidence rate of regurgitation and aspiration effectively.