Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Objective:To investigate the correlation between serum uric acid/high density lipoprotein cholesterol (URH) and diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM) .Methods:According to urinary albumin creatinine ratio, 171 patients with T2DM were divided into simple T2DM group (group A1), microalbuminuria group (group A2) and macroalbuminuria group (group A3). The general data, HbA1c, biochemical indices were compared, and URH was calculated.Results:The systolic blood pressure, diastolic blood pressure, SUA, TG and URH of A1 group were lower than those of the other two groups [ (129.7±15.78) vs (141.65±16.04) vs (147.31±17.01) mmHg, (78.9±10.71) vs (83.79±10.67) vs (84.61±12.19) mmHg, 291.5 (253.75, 351.25) vs 346 (280, 409) vs 344.5 (274.75, 425.75) μmol/L, 26.12 (19.71,32.96) vs 33.45 (26.55,42.2) vs 33.45 (26.55,42.2) ] ( P<0.05). HDL-C was higher than those of the other two groups [1.19 (1.02,1.29) vs1.02 (0.87,1.21) vs 1.07 (0.93,1.25) mmol/L] ( P<0.05), the course of disease and SCr of group A3 were higher than those of the other two groups [10.5 (7.25, 15) vs 8.5 (4,12) vs 8 (3,11) years; 82.5 (70.57,101.75) vs 66 (52.75,73.75) vs 64 (51, 84) μmol/L ] ( P<0.05), and eGFR was lower than those of the other two groups [91.63 (67.09, 112.21) vs 116.7 (96.6, 142.53) vs 109.85 (85.64, 152.39) ml/min/1.73 m 2] ( P<0.05). There were no significant differences in gender, smoking history, drinking history, age, BMI, TC, LDL-C, BUN, FPG or HbA1c among different groups (P> 0.05). Correlation analysis showed that the course of disease, systolic blood pressure, diastolic blood pressure, TG, SUA, URH were positively correlated with UACR, while HDL-C was negatively correlated with UACR. Logistic regression analysis showed that course of disease was a risk factor for macroproteinuria, while systolic blood pressure and URH were risk factors for microproteinuria and macroproteinuria. ROC curve showed that the AUC value of URH was the highest, and the accuracy rate was 69.3%. Conclusions:URH is closely related to the occurrence of DKD and is a risk factor of DKD. Dynamic monitoring of URH in T2DM patients is helpful for early screening of DKD, which is superior to SUA and HDL-C.

OBJECTIVE: To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout. METHODS: The Sidt2 knockout (Sidt2^-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed. RESULTS: Sidt2^-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2^-/- HL7702 cells. CONCLUSION Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.
Humans ; Lysosome-Associated Membrane Glycoproteins/metabolism* ; Autophagy ; Apoptosis ; Hepatocytes ; Lysosomes/metabolism* ; Chloroquine/pharmacology* ; Nucleotide Transport Proteins/metabolism*

OBJECTIVE: To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. METHODS: The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO₂/FiO₂), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. RESULTS: There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO₂/FiO₂, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). CONCLUSIONS Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.
Humans ; Retrospective Studies ; Alcoholism ; Prognosis ; Respiratory Distress Syndrome ; Pneumonia ; Sepsis ; Intensive Care Units ; Procalcitonin ; Fibrinogen ; ROC Curve

Objective:To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality.Methods:A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients.Results:A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95% CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. Conclusions:For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.

Objective:To investigate the effect of blocking P21 activated kinase 1 (PAK1) activity on the proliferation, differentiation, and apoptosis of acute megakaryocytic leukemia (AMKL) cell lines (CHRF and CMK) .Methods:Cell counts were used to detect the effects of PAK1 inhibitors (IPA-3 and G5555) on AMKL cell proliferation inhibition and colony formation, and flow cytometry was used to detect its effects on AMKL cell cycle. The effect of PAK1 inhibitor on the expression of cyclin D1 and apoptosis-related protein Cleaved caspase 3 was detected using Western blot, while interference with the protein expression level of PAK1 in AMKL cells was assessed using lentivirus-mediated shRNA transfection technology. Flow cytometry was used to detect the effects of knockdown of PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in AMKL cells.Results:PAK1 inhibitors inhibited the proliferation of AMKL cells in a dose-dependent manner and reduced the ability of cell colony formation, and the difference was statistically significant when compared with the control group ( P<0.05) . Moreover, they also reduced the percentage of AMKL cells in S phase, and Western blot detection showed that the expression levels of phosphorylated PAK1 and cyclin D1 decreased significantly. Finally, PAK1 inhibitors induced AMKL cell apoptosis by up-regulating Cleaved caspase 3 and showed different abilities to increase the content of polyploid DNA in megakaryocytes. Only high concentrations of IPA-3 and low doses of G5555 increased the number of polyploid megakaryocytes, while knockdown of PAK1 kinase activity promoted AMKL cell differentiation and increased the apoptosis rate. Conclusion:PAK1 inhibitor significantly arrests AMKL cell growth and promotes cell apoptosis. Knocking down the expression of PAK1 promotes the formation of polyploid DNA and induces AMKL cell apoptosis. The above findings indicate that inhibiting the activity of PAK1 may control AMKL effectively.

Objective:To investigate the relationship between the arterial blood lactic acid level after entering the intensive care unit (ICU) and the 28-day mortality of patients with septic shock.Methods:The clinical data of 303 patients with septic shock hospitalized in the department of critical medicine of the Affiliated Hospital of Jining Medical College from April 2015 to June 2019 were analyzed retrospectively. According to the blood lactate (Lac) level, the patients were divided into <4 mmol/L group ( n=203), 4-10 mmol/L group ( n=69) and >10 mmol/L group ( n=31). The baseline characteristics of the patients were analyzed. Multiple logistic regression analysis was used to analyze the independent influencing factors of the 28-day mortality of patients with septic shock. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of the Lac level after entering the ICU for 28-day mortality, and Kaplan-Meier survival curve was performed according to the best cut-off value. Results:A total of 303 patients with septic shock were included, with 179 died in 28 days, and the total mortality was 59.08%. There were 203, 69, 31 patients in Lac<4 mmol/L, 4-10 mmol/L and >10 mmol/L group, respectively. There were significant differences in Acute Physiology and Chronic Health Evalution Ⅱ (APACHE Ⅱ), Sequential Organ Failure Assessment (SOFA), oxygenation index (PaO 2/FiO 2), abdominal infection, the proportion of vasoactive drugs use among the three groups ( P<0.05). Multiple logistic regression analysis showed that the independent influencing factor of the 28-day mortality of septic shock were age, SOFA, use of mechanical ventilation, lactic acid (Lac). ROC curve analysis showed that the area under the ROC curve (AUC) for predicting 28-day mortality of patients with septic shock was 0.604 5 (95% CI: 0.540 8-0.668 2). When the optimal cut-off value was 3.55 mmol/L, the sensitivity was 0.508 4, the specificity was 0.733 9, the positive likelihood ratio was 1.910 3 and the negative likelihood ratio was 0.669 9. According to the best cut-off value of entrance Lac, patients were divided into high Lac group (≥3.55 mmol/L) and low Lac group (<3.55 mmol/L), and their 28-day mortality rates were 73.39%(91/124) and 49.16%(88/179). Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of the high Lac group was significantly lower than that of the low Lac group ( P<0.001). Multiple logistic regression analysis showed that after adjusting for confounding factors, the 28 d mortality increased to 1.22 times for each increase of 1 mmol/L of Lac [odds ratio ( OR)=1.22, 95% confidence interval (95% CI) was 1.08-1.37, P=0.001 4]. The 28 d mortality in high Lac group was 3.53 times higher than that in low Lac group ( OR=3.53, 95% CI was 1.36-7.09, P=0.000 4). Conclusions:In patients with ICU septic shock, the arterial blood Lac level after admission was associated with 28-day mortality. Patients with septic shock whose arterial blood Lac level exceeded 3.55 mmol/L within 1 hour of entering the room had a significantly increased risk of death.

Objective:Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data.Methods:Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank.Results:The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin ( P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion:The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.

Objective:To study the influencing factors of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM), and to explore the control countermeasures.Methods:The patients definitely diagnosed with T2DM in the Ophthalmology department from July 2017 to January 2019 were enrolled as subjects. The clinical data of patients were collected. According to eye examination results, they were divided into T2DM with DR group and T2DM without DR group. Clinical data of both groups were compared. Multivariate stepwise logistic regression analysis was performed to analyze the risk factors for DR in T2DM patients.Results:The proportion of diabetic nephropathy and diabetic peripheral neuropathy in T2DM with DR group was significantly higher than that in patients with T2DM without DR ( P<0.05). The T2DM duration, retinal arteriosclerosis, diastolic blood pressure (DBP), systolic blood pressure (SBP), glycosylated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) in T2DM with DR group were significantly higher than those in T2DM without DR group ( P<0.05). The postprandial 2h C-peptide in T2DM with DR group was significantly lower than that in T2DM without DR group ( P<0.05). Multivariate stepwise logistic regression analysis showed that diabetic nephropathy , diabetic peripheral neuropathy, T2DM duration, SBP, DBP, HbA1c and LDL-C were the influencing factor of DR. Conclusions:Diabetic nephropathy , diabetic peripheral neuropathy, T2DM duration, SBP, DBP, HbA1c and LDL-C are related to occurrence of DR. In the control, health education should be strengthened for high-risk populations with long T2DM duration. In the community management, the management for blood lipids, blood pressure and blood glucose in diabetic patients should be further strengthened.

OBJECTIVE: To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey. METHODS: Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members. RESULTS: Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet. CONCLUSION The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.
Adult ; Asian Continental Ancestry Group ; Heterozygote ; Humans ; Mutation ; Pedigree ; Phenotype ; Proteins ; genetics ; Spastic Paraplegia, Hereditary ; genetics