[Epidemiological investigation and risk factors of diabetic retinopathy in Yunnan Province].

To investigate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Yunnan Province, explore its risk factors, and provide a basis for the prevention and treatment of chronic complications of diabetes mellitus (DM). This is a large cross-sectional study, in all, 1 524 DM patients in 16 communities and villages of Yunnan Province who were registered in health service centers were included in this study from August to November 2019. All patients completed a uniform questionnaire, anthropometric measurements, biochemical measurements, and auxiliary examinations. Logistic regression analysis was used to screen the risk factors of DR. The prevalence rates of DR, mild non-proliferative DR (mild-NPDR), and referable DR (RDR) were 16.0% (244/1 524), 4.5% (69/1 524), and 11.5% (175/1 524), respectively. Glycated hemoglobin A1c (HbA1c)≥7.0% was the risk factor of mild-NPDR (OR=1.872, 95%CI 1.055-3.323) and RDR (OR=4.821, 95%CI 2.917-7.969). Blood pressure≥130/80 mmHg (1 mmHg=0.133 kPa) was the risk factor of mild-NPDR (OR=1.933, 95%CI 1.112-3.358) and RDR (OR=1.505, 95%CI 1.063-2.130). In Yunnan Province, 16.0% DM patients had accompanying DR, wherein about 71.7% of them required an ophthalmology referral, and the high incidence of RDR in DM patients was associated with poor control of blood glucose and blood pressure.

[Clinical and genetic mutation characteristics of patients with primary hemophagocytic lymphohistiocytosis and their impact on prognosis].

Objective: To investigate the clinical and genetic mutation characteristics of patients with primary hemophagocytic lymphohistiocytosis (HLH) and their impact on prognosis. Methods: Sixty-three primary HLH patients with complete medical records admitted and diagnosed at Beijing Friendship Hospital of Capital Medical University from January 2013 to December 2022 were selected. The patients' clinical and laboratory features, genetic and rapid immunological indicator characteristics, treatment outcomes and prognosis were retrospectively analyzed. Follow-up was up to June 30, 2023, with a median follow-up time [M (Q1, Q3)] of 47 (21, 76) months. Overall survival was analyzed using Kaplan-Meier survival curve, and prognostic factors were analyzed using Cox proportional hazards regression model. Results: Sixty-three primary HLH patients included 35 males and 28 females, with a median age [M (Q1, Q3)] of 17 (7, 27) years. Clinical manifestations at the initial diagnosis mainly included fever (93.7%, 59/63), splenomegaly (87.3%, 55/63), hemophagocytosis (65.1%, 41/63), hepatomegaly (52.4%, 33/63) and central nervous system (CNS) involvement (38.1%, 24/63). A total of 39 patients (61.9%) were diagnosed with EB virus (EBV) infection at initial diagnosis.PRF1 and UNC13D gene mutations were the most common mutations, and the highest frequency mutation site in the PRF1 gene was c.1349C>T, and that of UNC13D gene was c.2588G>A. A total of 76.2% (48/63) of patients had reduced activity of natural killer (NK) cells. Cytotoxic cell degranulation function was impaired or absent in 52.7% (29/55) of patients, of which 79.2% (19/24) of patients with primary HLH with defects in degranulation-related genes had impaired degranulation function. The 1-year and 3-year overall survival rates were 74.8% and 66.7%, respectively. Cox multivariate analysis suggested that peripheral blood EBV≥10 000 copies/ml (HR=3.523, 95%CI: 1.418-8.757, P=0.007) was the risk factor for prognosis. Conclusions: The main clinical manifestations of primary HLH patients at the initial diagnosis include fever, splenomegaly, hemophagocytosis, hepatomegaly, and CNS involvement. PRF1 and UNC13D are the most commonly mutated genes. High copy number EBV infection in peripheral blood is the risk factor for prognosis.

[Primary ciliary dyskinesia associated with a novel DNAH11 genetic variant: a case report].

Primary ciliary dyskinesia (PCD) is a heterogeneous genetic disorder associated with abnormalities in ciliary structure and function. Here, we report A 22-year-old non-smoking Chinese man with recurrent episodes of respiratory tract infections and sinusitis since high school period. The diagnosis is more complicated by the atypical symptoms and the late age of onset. We summarized the clinical characteristics of this case and literature review. This report aimed to improve the clinical understanding of primary ciliary dyskinesia.

Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations.

The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004-2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.

Host response of Nicotiana benthamiana to the parasitism of five populations of root-lesion nematode, Pratylenchus coffeae, from China.

In a recent survey of nematodes associated with tobacco in Shandong, China, the root-lesion nematode Pratylenchus coffeae was identified using a combination of morphology and molecular techniques. This nematode species is a serious parasite that damages a variety of plant species. The model plant benthi, Nicotiana benthamiana, is frequently used to study plant-disease interactions. However, it is not known whether this plant species is a host of P. coffeae. The objectives of this study were to evaluate the parasitism and pathogenicity of five populations of the root-lesion nematode P. coffeae on N. benthamiana.N. benthamiana seedlings with the same growth status were chosen and inoculated with 1,000 nematodes per pot. At 60 days after inoculation, the reproductive factors (Rf = final population densities (Pf)/initial population densities (Pi)) for P. coffeae in the rhizosphere of N. benthamiana were all more than 1, suggesting that N. benthamiana was a good host plant for P. coffeae.Nicotiana. benthamiana infected by P. coffeae showed weak growth, decreased tillering, high root reduction, and noticeable brown spots on the roots. Thus, we determined that the model plant N. benthamiana can be used to study plant-P. coffeae interactions.

[Clinical efficacy and safety analysis of 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer].

Objective: To investigate the clinical efficacy and safety of 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer. Methods: Clinical data of 36 patients who underwent CT-guided 125I seed implantation for mediastinal lymph node metastasis of lung cancer from August 2013 to April 2020 in three hospitals of the Northern radioactive particle implantation treatment collaboration group were retrospectively collected, including 24 males and 12 females, aged 46 to 84 years. Cox regression model was used to analyze the relationship between local control rate, survival rate and tumor stage, pathological type, postoperative D90, postoperative D100 and other variables, and to analyze the occurrence of complications. Results: The objective response rate of CT-guided 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer was 75% (27/36), the median control time was 12 months, the 1-year local control rate was 47.2% (17/36), and the median survival time was 17 months. The 1-year and 2-year survival rates were 61.1% (22/36) and 22.2% (8/36) respectively. Univariate analysis showed that in the treatment of mediastinal lymph node metastasis with CT-guided 125I implantation, factors related to local control included tumor stage (HR=5.246, 95%CI: 2.243-12.268, P<0.001), postoperative D90 (HR=0.191, 95%CI: 0.085-0.431, P<0.001), postoperative D100 (HR=0.240, 95%CI: 0.108-0.533, P<0.001); The factors affecting survival were tumor stage (HR=2.712, 95%CI: 1.356-5.425, P=0.005), postoperative D90 (HR=0.110, 95%CI: 0.041-0.294, P<0.001), postoperative D100 (HR=0.212, 95%CI: 0.092-0.489, P<0.001). Multivariate analysis showed that tumor stage (HR=5.305, 95%CI: 2.187-12.872, P<0.001) and postoperative D100 (HR=0.237, 95%CI: 0.099-0.568, P<0.001) were correlated with local control rate. Tumor stage (HR=2.347, 95%CI: 1.095-5.032, P=0.028) and postoperative D90 (HR=0.144, 95%CI: 0.051-0.410, P<0.001) were correlated with survival. In terms of complications, 9 of the 36 patients had pneumothorax, and 1 of them was cured by closed thoracic drainage for severe pneumothorax; 5 cases developed pulmonary hemorrhage and 5 cases developed hemoptysis, which recovered after hemostasis treatment. One case developed pulmonary infection and recovered after anti-inflammatory treatment. No radiation esophagitis and radiation pneumonia occurred; No grade 3 or higher complications occurred. Conclusion: 125I seed implantation in the treatment of lung cancer mediastinal lymph node metastasis has a high local control rate and controllable adverse effects.

[Effect of Friday surgery on clinical outcome of elderly patients with hip fracture under multidisciplinary treatment].

Objective: To assess the impact of Friday surgery on clinical outcomes in elderly patients with hip fracture under multidisciplinary treatment. Methods: A retrospective cohort study. The clinical data of 414 geriatric patients with hip fractures admitted to Zhongda Hospital Affiliated with Southeast University from January 2018 to March 2021 were analyzed retrospectively, including 126 males and 288 females with a mean age of (81.3±7.6) years. The patients were divided into two groups based on whether they underwent surgery on Friday or not. The Friday group(n=69) and the non-Friday group(n=345) were compared in terms of general information, American Society of Anesthesiologists(ASA) classification, fracture type, injury to admission time, preoperative waiting time, surgical method, anesthesia type and use of intensive care unit (ICU) fast track. Propensity score matching (PSM) was performed based on age, ASA grade, time from injury to admission, preoperative waiting time, hemoglobin and albumin levels at admission. Clinical outcomes were collected and compared between the two groups, including length of hospital stay, total hospitalization cost and 30-day, 90-day and 1-year mortality rates, and postoperative complications. Multivariate logistic regression analyses were conducted to identify influencing factors for 1-year mortality in geriatric patients with hip fracture. Results: Baseline data showed statistically significant differences in hemoglobin, albumin and preoperative waiting time between the two groups (all P<0.05). After PSM matching, 69 patients were included in each group, and no significant differences were observed in baseline data between the two groups (all P>0.05). There was no significant differences in 30-day mortality rate (4.3% vs 0, P=0.080), 90-day mortality rate (7.2% vs 1.4%, P=0.095), length of hospital stay [(10.85±4.45)d vs (10.92±3.68)d, P=0.919], total hospitalization cost [(60.9±15.4) thousands yuan vs (59.1±15.4) thousands yuan, P=0.489], postoperative complications [pneumonia (11.6% vs 13.0%, P=0.796), cardio-cerebrovascular complications (11.6% vs 8.7%, P=0.573) and delirium (5.7% vs 2.9%, P=0.245)] between the Friday group and the non-Friday group (all P>0.05). However, the 1-year mortality rate was higher in the Friday group than that in the non-Friday group(18.8% vs 4.3%, P=0.008). Multivariate analysis revealed that surgery on Friday (OR=11.222, 95%CI: 2.198-57.291, P=0.004), low hemoglobin levels at admission (OR=0.920, 95%CI: 0.875-0.967, P=0.001), hemiarthroplasty treatment (OR=5.127, 95%CI: 1.308-20.095, P=0.019) and longer surgery duration (OR=0.958, 95%CI: 0.927-0.989, P=0.009) were influencing factors for 1-year mortality in geriatric patients with hip fracture. Conclusions: In the context of multidisciplinary treatment, Friday surgery does not increase short-term mortality, length of hospital stay, total hospitalization cost or incidence of complications in geriatric patients with hip fracture. However, it remains a influencing factor for 1-year mortality in those patients.

[Association between obstructive sleep apnea and vascular injury in hypertensive patients].

Objective: To investigate the relationship between obstructive sleep apnea (OSA), apnea hypopnea index (AHI) and vascular injury in hypertensive patients. Methods: This cross-sectional study enrolled patients admitted to the Hypertension Department of TEDA International Cardiovascular Hospital from April 2020 to April 2023, who finished portable sleep monitoring. Sleep monitoring indicators, flow-mediated vasodilation (FMD), carotid artery ultrasound, carotid intima-media thickness, cervical and femoral pulse wave conduction velocity (cfPWV), brachial and ankle pulse wave conduction velocity (baPWV) were analyzed. OSA was classified into mild (5 times/h≤AHI<15 times/h), moderate (15≤AHI<30 times/h), and severe (AHI≥30 times/h) based on AHI levels. FMD<6.0% was defined as vascular endothelial injury, and cfPWV>10 m/s and/or baPWV>18 m/s was defined as arterial stiffness. Multivariate logistic regression analysis was used to explore the correlation between AHI, OSA severity and vascular injury, and subgroup analysis was performed in young (age≤45 years) and middle-to-old patients (age>45 years). Sensitivity analysis was performed by excluding patients with diabetes, cerebrovascular disease and coronary heart disease. The correlation between AHI and vascular injury index was analyzed by restricted cubic spline. Results: A total of 555 adult hypertensive patients were included, the mean age was (39.7±9.2) years, 422 were males (76.0%), and the prevalence of OSA was 66.7% (370/555). Multivariate logistic regression analysis showed that moderate OSA (OR=2.83, P=0.019) and severe OSA (OR=3.40, P=0.016) were positively correlated with vascular endothelial injury after adjusting for age, sex, body mass index and mean arterial pressure. Subgroup analysis showed that log AHI (OR=1.99, P=0.035), moderate OSA (OR=4.83, P=0.010) and severe OSA (OR=4.64, P=0.015) were associated with vascular endothelial injury in young hypertensive patients. The results of sensitivity analysis were similar to the above results. The results of restricted cubic spline analysis showed that AHI was correlated with FMD (P=0.022), and the slope of the curve was the largest when AHI was between 0 and 10 times/h. There was no correlation between log AHI and OSA severity and carotid intima-media thickening and arterial stiffness (all P<0.05). Conclusions: OSA is associated with vascular endothelial injury in hypertensive patients, especially in young patients.

[Long-term outcome of EVAHEART I implantable ventricular assist device for the treatment of end stage heart failure: clinical 3-year follow-up results of 15 cases].

Objective: To evaluate the long-term efficacy and safety of the implantable ventricular assist system EVAHEART I in clinical use. Methods: Fifteen consecutive patients with end-stage heart failure who received left ventricular assist device therapy in Fuwai Hospital from January 2018 to December 2021 were enrolled in this study, their clinical data were retrospectively analyzed. Cardiac function, liver and kidney function, New York Heart Association (NYHA) classification, 6-minute walk distance and quality of life were evaluated before implantation and at 1, 6, 12, 24 and 36 months after device implantation. Drive cable infection, hemolysis, cerebrovascular events, mechanical failure, abnormally high-power consumption and abnormal pump flow were recorded during follow up. Results: All 15 patients were male, mean average age was (43.0±7.5) years, including 11 cases of dilated cardiomyopathy, 2 cases of ischemic cardiomyopathy, and 2 cases of valvular heart disease. All patients were hemodynamically stable on more than one intravenous vasoactive drugs, and 3 patients were supported by preoperative intra aortic balloon pump (IABP). Compared with before device implantation, left ventricular end-diastolic dimension (LVEDD) was significantly decreased ((80.93±6.69) mm vs. (63.73±6.31) mm, P<0.05), brain natriuretic peptide (BNP), total bilirubin and creatinine were also significantly decreased ((3 544.85±1 723.77) ng/L vs. (770.80±406.39) ng/L; (21.28±10.51) µmol/L vs. (17.39±7.68) µmol/L; (95.82±34.88) µmol/L vs. (77.32±43.81) µmol/L; P<0.05) at 1 week after device implantation. All patients in this group were in NYHA class Ⅳ before implantation, and 9 patients could recover to NYHA class Ⅲ, 3 to class Ⅱ, and 3 to class Ⅰ at 1 month after operation. All patients recovered to class Ⅰ-Ⅱ at 6 months after operation. The 6-minute walk distance, total quality of life and visual analogue scale were significantly increased and improved at 1 month after implantation compared with those before operation (P<0.05). All patients were implanted with EVAHEART I at speeds between 1 700-1 950 rpm, flow rates between 3.2-4.5 L/min, power consumption of 3-9 W. The 1-year, 2-year, and 3-year survival rates were 100%, 87%, and 80%, respectively. Three patients died of multiple organ failure at 412, 610, and 872 d after surgery, respectively. During long-term device carrying, 3 patients developed drive cable infection on 170, 220, and 475 d after surgery, respectively, and were cured by dressing change. One patient underwent heart transplantation at 155 d after surgery due to bacteremia. Three patients developed transient ischemic attack and 1 patient developed hemorrhagic stroke events, all cured without sequelae. Conclusion: EVAHEART I implantable left heart assist system can effectively treat critically ill patients with end-stage heart failure, can be carried for long-term life and significantly improve the survival rate, with clear clinical efficacy.

[Effects of manipulator operation task and troubleshooting task on blood pressure indexes of oceanauts].

Objective: To explore the characteristics and rules of blood pressure changes in oceanauts during simulated operation of manipulator and troubleshooting tasks with different difficulty. Methods: In July 2020, 8 deep-sea manned submersible oceanauts, 6 males and 2 females, were selected as objects. In the 1∶1 model of Jiaolong deep-sea manned submersible, the oceanauts performed manipulator operation tasks and troubleshooting tasks with different difficulties, measured the continuous blood pressure of the oceanauts, filled in the NASA Task Load Index (NASA-TLX scale) after the completion of a single mission, and the changes of systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP) and mental workload were analyzed. Results: In a single task, the SBP, DBP and MAP of the oceanauts increased first and then decreased. The blood pressure values at the third minute were significantly lower than those at the first minute (P<0.01), and those at the fifth minute were significantly higher than those at the third minute (P<0.01). When performing the same task, compared with the quiet state, SBP, DBP and MAP increased when the oceanauts performed low difficulty, high difficulty, high difficulty+2-back manipulator operation task and troubleshooting task (P<0.05). When the task difficulty was the same, the SBP and MAP of oceanauts performing manipulator operation tasks were higher than those of oceanauts performing troubleshooting tasks (P<0.05). Compared with low difficulty tasks, the scores of NASA-TLX scale for oceanauts performing high difficulty manipulator operationtasks were significantly higher (P<0.05). Compared with the low difficulty task and high difficulty task, the scale score of the high difficulty+2-back troubleshooting task was significantly higher (P<0.05). When the task difficulty was the same, the scale scores of low difficulty and high difficulty manipulator operation tasks were significantly higher than those of troubleshooting tasks (P<0.05). SBP, DBP, MAP of No. 1, No. 3, No. 4, No. 5, and No. 7 oceanauts (all of whom had 6 years of diving) were positively correlated with NASA-TLX scale scores (r>0.8, P<0.05) . Conclusion: In the process of manned deep-sea diving, when the oceanauts perform manipulator operation tasks and troubleshooting tasks, with the increase of task difficulty, the mental load of oceanauts increases, and the blood pressure index increases significantly in a short time. At the same time, improving the proficiency of operation can reduce the variation range of blood pressure indexes. Blood pressure can be used as an effective reference to evaluate the difficulty of operation and guide scientific training.

[A case of dimethylformamide poisoning caused by skin contact].

In this paper, the clinical data of a case of accidental poisoning of dimethylformamide in a traffic accident was analyzed. The patient was trapped in the driving room, his limbs were soaked in dimethylformamide for a long time, and dimethylformamide was inhaled at the same time. After 4 days of treatment in a local hospital, he was transferred to the Department of Poisoning & Occupational Diseases, Emergency Medicine of Qilu Hospital of Shandong University for treatment. The main clinical manifestation of the patient was liver damage and intractable abdominal pain, which was cured by active treatment.

DOCK4 regulates ghrelin production in gastric X/A-like cells.

PURPOSE: Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. Ghrelin also modulates neuroinflammatory and apoptotic processes. Dedicator of cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor (GEF), is involved in the regulation of neuronal polarization and axon regeneration. However, the effect of DOCK4 on ghrelin production has not been explored. METHODS: The expression of DOCK4 in human and mouse stomach was examined by immunohistochemical staining. The synthesis and secretion of ghrelin in Dock4 null mice were evaluated by real-time quantitative PCR, Western blot and ELISA. The effects of DOCK4 on ghrelin production in mHypoE-42 cells were measured by real-time quantitative PCR and Western blot. RESULTS: We showed that DOCK4 was expressed in both human and mouse gastric ghrelin cells. The mRNA and protein levels of gastric ghrelin, as well as ghrelin secretion, were remarkably diminished in Dock4 null mice. Furthermore, we showed that overexpression of Dock4 significantly stimulated ghrelin expression, while siRNA knockdown of endogenous Dock4 resulted in a marked decrease of ghrelin in mHypoE-N42 cells. CONCLUSIONS: Our results identify DOCK4 as a critical regulator for ghrelin production in gastric X/A-like cells.

[Consistency analysis and clinical guiding significance of cytomegalovirus nucleic acid and antibody detections in patients with different clinical characteristics].

OBJECTIVE: To investigate the consistency of cytomegalovirus deoxyribo nucleic acid (CMV-DNA) and immunoglobulin M (IgM) antibody detections in patients with different clinical characteristics and their guiding value for clinical practice. METHODS: From December 2014 to November 2019, a total of 507 patients who were detected with both CMV-IgM and CMV-DNA were collected in Peking University International Hospital. Their general information, such as gender, age and clinical data, including the patient's diagnosis, medication, and outcome were also collected. The groups were stratified according to whether CMV-DNA was negative or positive, CMV-IgM was negative or positive, age, gender, and whether they received immunosuppressive therapy or not. The Pearson Chi-square test or Fisher's exact test was used for comparison of the rates between the groups. P < 0.05 means the difference is statisti-cally significant. RESULTS: Of the 507 patients submitted for examination, 55 (10.85%) were positive for CMV-DNA, 74 (14.60%) were positive for CMV-IgM, and 20 (3.94%) were positive for both CMV-DNA and CMV-IgM. Of the 55 patients with CMV-DNA positive, 37 were male, accounting for 67.27%. In addition, 25 patients were older than 60 years, accounting for 45.45% and 33 patients received immunosuppressive therapy, accounting for 60%. The rates were higher than that of CMV-DNA negative group, 47.35% (P=0.005), 68.14% (P=0.043), 46.02% (P=0.050), respectively. Of the patients with both CMV-DNA and IgM positive, 45% received immunosuppressive threapy, which was lower than that of CMV-DNA positive but IgM negative patients (68.57%, P=0.086), and also lower than CMV-DNA negative but IgM positive patients (68.52%, P=0.064). In the patients with both CMV-DNA and IgM positive, 91.67% showed remission after receiving ganciclovir, whereas in the patients with CMV-DNA positive but IgM negative, the rate was only 60% (P=0.067). CONCLUSION: CMV-IgM antibody detection is affected by age, gender, and immune status. It is not recommended to use CMV-IgM alone to determine CMV infection in patients with immunosuppressive status and those older than 60 years. CMV-DNA and CMV-IgM combined detection may help to predict patients' immune status and outcomes of antiviral therapy.

[Cortical thickness and cognitive impairment in patients with amyotrophic lateral sclerosis].

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with high morbidity and mortality. There are about 5%-15% of ALS patients combining with frontotemporal lobe degeneration (FTLD) at the same time and 50% of patients combing with cognitive function changes. The analysis of cortical thickness based on MRI is an important imaging method to evaluate brain structure. The aim of the study was to explore the changes of brain structure in ALS patients by cortical thickness analysis, and to explore the correlation between the brain structure and cognitive function. METHODS: In the study, 18 ALS patients treated in Department of Neurology, Peking University Third Hospital and 18 normal controls (age, gender and education level matched) were included. 3D magnetization prepared rapid gradient echo imaging (MPRAGE) sequence MRI was performed and the cortical thickness was analyzed. At the same time, all the ALS patients took neuropsychology assessments, including: mini-mental state examination (MMSE), verbal fluency test (VFT), Stroop color word test (SCWT), prospective memory (PM), emotional picture perception and recognition, and faux pas story test. RESULTS: After cognitive assessment, two ALS patients had cognitive impairment. One was in accordance with ALS-frontotemporal dementia (FTD) diagnosis and the other one was in accordance with ALS cognitive impairment (ALSci) diagnosis. In all the 18 ALS patients and 18 normal controls, the cortical thickness of the left medial orbitofrontal lobe and the medial temporal lobe were significantly reduced (P < 0.05) in ALS group by the vertex-wise comparison. Cortical thickness of the left entorhinal cortex, the left inferior temporal gyrus, the left medial orbitofrontal lobe and the left insular lobe was significantly reduced (P < 0.05) by the region-wise comparison. However, when only concluded the 16 ALS non-cognitive impairment patients, there was no significant difference between the two groups (P>0.05). There were correlations between the scores of prospective memory, emotional picture perception and recognition, faux pas story test and the cortical thickness of their corresponding regions (P < 0.05). CONCLUSION: The cortical thickness of ALS patients are correlated with neuropsychological scores which may reflect the changes of cortical structure corresponding to the cognitive assessment, and may provide help for the early diagnosis of cognitive changes in ALS patients.

[Clinical efficacy of 585 nm Q-switched laser treatment on inflammatory lesion and postinflammatory erythema of acne vulgaris].

OBJECTIVE: To evaluate the efficacy and safety of 585 nm Q-switched laser in the treatment of acne inflammatory lesions and postinflammatory erythema. METHODS: A total of 25 patients with moderate facial acne, symmetrical distribution of inflammatory lesions and postinflammatory erythema on both sides of the face, were enrolled. Among the 25 patients, 22 patients completed all the treatment and evaluation, and 3 patients were lost to follow-up. 585 nm Q-switched laser was used on a randomly selected side of the face for three times of treatment at a 2 week interval. The evaluations were made before each treatment, 2 and 4 weeks after the last treatment, therefore the evaluation time points were before the treatment, weeks 2, 4, 6, and 8, respectively, for a total of 5 times. Acne severity was assessed using the investigator' s global assessment (IGA) score, and erythema severity was assessed using the investigator' s subjective erythema score and narrow-spectrum reflectance spectrophotometer at each follow-up. RESULTS: After 3 times of treatment, there was statistically significant difference between the IGA score in week 8 and before treatment on both sides(Z=2.64, P < 0.01; Z=2.67, P < 0.01). There was no significant difference in IGA score between the treatment side and the control side before treatment and in week 8 (P=0.59, P=0.26). There was statistically significant difference between the investiga-tor' s subjective erythema score in week 8 and before treatment on the treatment side(Z=4.24, P < 0.01), while no significant difference was showed on the control side(Z=1.73, P=0.08). In week 8, the investigator's subjective erythema score of the treatment side was lower than that of the control side (Z=3.61, P < 0.01). The erythema index of the treatment side was significantly decreased at 5 time points (P < 0.01), and the index decreased significantly in week 8 compared with the index before treatment (P < 0.01), while the erythema index of the control side was not significantly different at 5 time points. The treatment related adverse events included erythema and edema after treatment and pain during treatment, the severity was mild to moderate, which resolved spontaneously within 1 to 3 days. Nine patients were very satisfied with the treatment, 7 patients were satisfied, and 6 patients considered average. CONCLUSION: 585 nm Q-switched laser has some effect in the treatment of postinflammatory erythema, and it ensures good tolerance and safety. There was no statistically significant difference between the treatment side and the control side on the improvement of acne inflammatory lesions.

[Effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion in mice].

Objective: To explore the effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion injury in mice. Methods: One hundred 10-Week-old healthy KM mice of SPF grade, weighing 25-28 g, were divided into 5 groups by the random number table method: sham group, focal cerebral ischemia group (I/R group), intermittent fasting group (IF group), metformin group (Met group), metformin+intermittent fasting group (Met+IF group). In IF group, food was provided ad libitum from 8∶00 to 16∶00 daily, but the mice were fasted for the rest of the time. In Met group, the mice underwent intraperitoneal injection of metformin (10 mg/kg). In Met+IF group, the mice received the same eating method as the IF group and the same method of metformin injection as Met Group. In Sham group, I/R group and IF group, the mice were intraperitoneally injected with equal volume of normal saline. Mice in all groups were not restricted to drinking water. Random plasma glucose and body weight changes in mice during preconditioning were monitored, and a focal cerebral ischemia-reperfusion model was established 14 days later. The cerebral infarction volume was measured after 1 hour of ischemia and 24 hours of reperfusion. The brain tissues of mice were subjected to Western blot to detect the contents of endoplasmic reticulum stress-related proteins, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and apoptosis proteins (Caspase-3 and Cleaved-caspase 3). Results: After different interventions, there was no significant difference in random plasma glucose changes among the four groups (all P<0.05). The blood glucose level of the mice in the Met+IF group was lower than the sham group, I/R group, IF group and Met group (all P<0.05). GRP78/ß-actin in sham group, I/R group, IF group, Met group, IF+Met group were 0.48±0.05, 1.35±0.10, 0.94±0.05, 0.70±0.14, 0.41±0.37, respectively; CHOP/ß-actin were 0.27±0.04, 1.03±0.03, 0.72±0.04, 0.63±0.04, 0.44±0.01, respectively; Caspase-3/ß-actin were 0.51±0.04, 1.04±0.04, 0.83±0.03, 0.76±0.03, 0.63±0.05, respectively; Cleaved-Caspase-3/ß-actin were 0.17±0.06, 1.01±0.20, 0.75±0.06, 0.51±0.12, 0.29±0.08, respectively, with statistically significant differences (all P<0.001). The counts of GRP78-positive cells in the hippocampus immunohistochemistry in the sham group, I/R group, IF group, Met group, and IF+Met group were 53±5, 192±11, 162±12, 140±10, 114±13, respectively, while the counts of CHOP-positive cells were 35±4, 177±12, 120±12, 100±7, 69±10, respectively, with statistically significant differences (all P<0.001). The relative volume of cerebral infarction in I/R group, IF group, Met group and IF+Met group were 0, 0.333±0.046, 0.258±0.023, 0.116±0.039, 0.111±0.039, respectively, and there were statistically significant differences (all P<0.001). Conclusion: Both Metformin and intermittent fasting can alleviate endoplasmic reticulum stress after cerebral ischemia and reperfusion in mice, and the combination of the two has a better effect.

[Clinical research in cell therapy of liver diseases: progress and challenges].

The high incidence of chronic liver disease is a serious threat to public health, and the current comprehensive internal medicine treatment is ineffective. Liver transplantation is limited by the shortage of liver source and post-transplant rejection, and thus unmet the clinical needs. More importantly, cell therapy shows great promise for the treatment of chronic liver disease. Over recent years, domestic and foreign scholars have carried out a variety of cell therapy preclinical and clinical trials for critical liver disease, and achieved certain results, providing new methods for the treatment of chronic liver diseases. This review discusses the cell therapy research status and application progress, various existing problems and challenges, and key issues of mesenchymal stem cells in the treatment of chronic liver diseases.

[Exploring the effects of entecavir treatment on the degree of liver fibrosis in patients with non-alcoholic fatty liver combined with chronic hepatitis B in Tibet region].

Objective: To explore the efficacy of entecavir antiviral therapy on the degree of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with chronic hepatitis B (CHB) in Tibet region. Methods: HBeAg-positive CHB patients who were treated with entecavir in the outpatient and inpatient Department of Infectious Diseases of the Tibet Autonomous Region people's Hospital between January 2018 to December 2019 were retrospectively analyzed. Among the 140 subjects with CHB, 95 cases were CHB alone, and the other 45 cases were diagnosed as CHB combined with NAFLD by ultrasound. All patients were given entecavir 0.5 mg orally once daily on an empty stomach for 48 weeks. HBeAg negative conversion rate, blood glucose, blood lipid, liver function and the degree of liver fibrosis were compared between the two groups at the 12th, 24th and 48th weeks of treatment to evaluate the virological response. SPSS 19.0 statistical software was used to process the data. Measurement data were expressed as mean ± standard deviation (x¯±s). Descriptive statistical analysis was used for t-test, and the categorical variables were expressed as percentage (%) and χ2 test. A p-value < 0.05 was considered as statistically significant. Results: After 48 weeks of treatment, the HBeAg and HBV DNA negative conversion rate were significantly better in patients with CHB alone (group B) than CHB combined with NAFLD (group A), that is to say, HBeAg negative conversion rate in group A and B patients were 28.90% and 40%, respectively, and group B was better than group A. HBV DNA negative conversion rate was significantly elevated in group B (83.2%) than group A (64.4%), with statistical significance (P<0.05), and the difference between the both groups was statistically significant. Alanine aminotransferase level was significantly decreased in patients with CHB alone than patients with CHB combined with NAFLD. Aspartate aminotransferase/platelet ratio index was significantly decreased after treatment than before treatment in both group of patients, and the depletion was more pronounced in CHB alone group. Liver stiffness values were significantly decreased in patients with CHB combined with NAFLD than CHB alone group. Moreover, liver stiffness values was higher in group A than group B before treatment under the influence of fat attenuation factors, and the differences before treatment and after treatment were 3.50±4.66 and 2.05±2.53, respectively; however, group B was not affected by fat attenuation factors, so LSM value reduction in group A was more obvious, and the differences were statistically significant. There was no statistically significant difference in blood glucose and blood lipids levels before and after treatment between the two groups. Conclusion: NAFLD has a certain effect on antiviral therapy and liver fibrosis in patients with CHB, i.e., the effect of antiviral therapy in patients with CHB alone is better than patients with CHB combined with NAFLD. Patients with CHB combined with NAFLD when treated with antiviral therapy had a significantly greater degree of liver stiffness reduction than patients with CHB alone. Therefore, it is necessary to actively intervene the risk factors associated with NAFLD according to the actual situation of different individuals to improve clinical efficacy of antiviral therapy.

[Progress in clinical diagnosis and treatment of multiple primary lung cancer].

With the application of high-resolution chest imaging system and lung cancer screening program, patients with multiple primary lung cancer (MPLC) are becoming a growing population in clinical practice. However, the diagnostic criteria of MPLC and its differentiation from intrapulmonary metastasis of lung cancer (IM) are still controversial, especially in cases with similar histology. On the basis of reviewing the existing literature, this paper discusses the changes of the diagnostic criteria of MPLC and the differential diagnosis methods of imaging, histology and molecular genetics of MPLC and IM, and briefly introduces the application of multidisciplinary diagnosis, algorithm, predictive model and artificial intelligence in the differential diagnosis of MPLC. In addition, we also discuss the latest progress in the treatment of MPLC. Radical surgery is the main method for the treatment of MPLC. Stereotactic body radiation therapy (SBRT) is safe and feasible for inoperable MPLC patients, and targeted therapy and immunotherapy can also be used in MPLC after appropriate patient selection.

[Screening and preliminary validation of biomarkers in sputum-negative pulmonary tuberculosis based on positron emission tomography/computed tomography and transcriptomics].

Objective: To screen and perform preliminary clinical validation of biomarkers of activity based on positron emission tomography/computed tomography (PET-CT) and transcriptomics in sputum-negative pulmonary tuberculosis lesion tissue. Methods: Nine patients with sputum-negative pulmonary tuberculosis treated surgically at the Shanghai Public Health Clinical Center for Thoracic Surgery from January 1, 2017 to December 31, 2019 were retrospectively collected as the discovery group, including four males and five females, aged 20-57 years (mean 36 years). All of the patients underwent PET-CT scanning before surgery, and the resected specimens were postoperatively classified according to preoperative PET-CT. The resected specimens were divided into areas with increased fluorodeoxyglucose (FDG) metabolism (SUVmax>3) and areas with normal FDG metabolism (SUVmax ≤ 3) according to the preoperative PET-CT performance. After sample processing, total RNA was extracted from the tissues of different regions, and then whole gene transcriptome sequencing was performed. Bioinformatics analysis of the two sets of data was performed to discover the expression profiles of the differences in whole gene transcriptome data between the two regions and to screen for candidate biomarkers. Eighty patients with sputum-negative pulmonary tuberculosis admitted to Shanghai Public Health Clinical Center from January 1, 2019 to January 1, 2021 were retrospectively collected as the validation group, including 37 males and 43 females, aged 20-62 years, with an average age of 39 years. The validation group was divided into a group with increased SUV (n=40) and a group without lesions on CT imaging (n=40). Enzyme-linked immunosorbent assay (ELISA) was used to determine the protein levels of candidate biomarkers in the peripheral plasma of patients. The effect of biomarkers was assessed using subject operating characteristic (ROC) curves. Student's t-test was used to determine whether the difference in protein levels between the two groups was statistically significant. Results: Bioinformatics analysis revealed that the expression levels of C1QB, CCL19, CCL5 and HLA-DMB correlated with the metabolic activity of sputum-negative tuberculosis lesion tissue. Further screening and validation by the validation group confirmed that the difference in C1QB protein levels in the peripheral plasma of patients was statistically significant between the group with increased SUV and the group without lesions on CT imaging [(3.55±0.34) mg/L vs. (2.75±0.21) mg/L, t=4.12, P<0.001]. And the ROC curve showed that the area under the curve for C1QB protein levels was 0.731, which had potential clinical value. Conclusion: The C1QB protein level can be used to assess the activity of lesions in patients with sputum-negative tuberculosis and is a potential biomarker.