[Association of urinary cadmium level with body mass index and body circumferences among older adults over 65 years old in 9 longevity areas of China].

Objective: To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China. Methods: Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 µg/g·creatinine, middle:0.77-1.69 µg/g·creatinine, high:≥1.69 µg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model. Results: The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) µg/g·creatinine, and the BMI was (22.70±3.82) kg/m2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 µg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI (Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference (Plinear<0.001), hip circumference (Plinear<0.001), and calf circumference (Plinear<0.001). Conclusion: Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

[Abnormal changes of static and dynamic functional connectivity of dopaminergic midbrain in patients with first-episode schizophrenia and their correlations with clinical symptoms].

Objective: To investigate the abnormal changes of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in the dopaminergic midbrain (ventral dorsal tegmental area and bilateral substantia nigra compacta, VTA/SNc) in patients with first-episode schizophrenia(SCH), and their correlation with the Positive and Negative Symptom Scale (PANSS). Methods: The data of 198 first-episode untreated schizophrenia patients and 199 healthy controls (HC) matched by age, sex and years of education who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2019 to May 2022 were prospectively collected. All subjects underwent high resolution structural MRI and resting state functional magnetic resonance imaging (rs-fMRI) scanning. The dopaminergic midbrain (VTA/SNc) was defined as three regions of interest (ROI). The sFC and dFC analyses with VTA/SNc as seeds were performed to produce a whole-brain diagram initially, which subsequently were compared between schizophrenia group and HC group. Finally, the correlation analysis of sFC and dFC values with the PANSS scores were performed, including the positive scale score, negative scale score, general psychopathology scale score, total score and symptom scores. Results: There were 86 males and 112 females in SCH group, and aged (23±9) years. Meanwhile, there were 95 males and 104 females in HC group, and aged (22±5) years. In the SCH group, the positive (P), the negative (N) and the general psychopathology (G) scale scores and the total score (T) of the PANSS scale was 20±7, 21±7, 41±11 and 82±22, respectively. Compared with the HC group, the VTA showed decreased sFC with four clusters including cerebellar vermis 7/9, left putamen, right thalamus and left middle cingulate gyrus in the schizophrenia group (peak center, t=-4.35, -4.81, -4.35 and -4.65; voxel P<0.005; cluster P<0.05), the right SNc showed decreased sFC with four clusters including left cerebellar hemisphere 4/5/8, right putamen, right medial orbitofrontal gyrus and the left putamen in the schizophrenia group (peak center, t=-4.91, -5.15, -4.77 and -5.21; voxel P<0.005; cluster P<0.05), and the left SNc showed decreased sFC with four clusters including the left putamen, right putamen, right medial orbitofrontal gyrus and left middle cingulate gyrus in the schizophrenia group (peak center, t=-5.82, -4.83 and -4.65; voxel P<0.005; cluster P<0.05). Compared with the HC group, the VTA showed decreased dFC with the right inferior parietal gyrus, right angular gyrus and right superior parietal gyrus in schizophrenia group (t=-4.17). In the schizophrenia group, the sFC value of cluster 2 (left putamen) with VTA as seed and cluster 4 (left putamen) with right SNc as seed were positively correlated with the positive scale scores in PANSS (r=0.141, 0.169, both P<0.05). The sFC and dFC values of significant regions were also correlated with hallucination, delusion, suspicion, hostility, communication disorder, passivity/indifference, lack of communication, stereotyped thinking, depression, non-cooperation, lack of judgment and insight, impulse control disorder, active social avoidance (all P<0.05). Conclusion: The static and dynamic functional connectivity (stability) of VTA/SNc to cerebellum, thalamus, striatum, prefrontal lobe and cingulate gyrus in first-episode schizophrenia patients were decreased, which were closely related to the positive and negative symptoms of schizophrenia.

Hexavalent chromium induces centrosome amplification through ROS-ATF6-PLK4 pathway in colon cancer cells.

Centrosome amplification (CA) refers to a numerical increase in centrosomes resulting in cells with more than two centrosomes. CA has been shown to initiate tumorigenesis and increase the invasive potential of cancer cells in genetically modified experimental models. Hexavalent chromium is a recognized carcinogen that causes CA and tumorigenesis as well as promotes cancer metastasis. Thus, CA appears to be a biological link between chromium and cancer. In the present study, we investigated how chromium triggers CA. Our results showed that a subtoxic concentration of chromium-induced CA in HCT116 colon cancer cells, resulted in the production of reactive oxygen species (ROS), activated ATF6 without causing endoplasmic reticulum stress, and upregulated the protein level of PLK4. Inhibition of ROS production, ATF6 activation, or PLK4 upregulation attenuated CA. Inhibition of ROS using N-acetyl-l-cysteine (NAC) inhibited chromium-induced activation of ATF6 and upregulation of PLK4. ATF6-specific siRNA knocked down the protein level and activation of ATF6, and upregulated PLK4, with no effect on ROS production. Knockdown of PLK4 protein had no effect on chromium-induced ROS production or activation of ATF6. In conclusion, our results suggest that hexavalent chromium induces CA via the ROS-ATF6-PLK4 pathway and provides molecular targets for inhibiting chromium-mediated CA, which may be useful for the assessment of CA in chromium-promoted tumorigenesis and cancer cell metastasis.

The binding between NPM and H2B proteins signals for the diabetes-associated centrosome amplification.

Diabetes not only increases the risk for cancer but also promotes cancer metastasis. Centrosome amplification (CA) is sufficient to initiate tumorigenesis and can enhance the invasion potential of cancer cells. We have reported that diabetes can induce CA, with diabetic pathophysiological factors as the triggers, which involves the signaling of nucleophosmin (NPM). Thus, CA can serve as a candidate biological link between diabetes and cancer. In the present study, we attempted to identify the NPM binding partners and investigated whether the binding between NPM and its partner mediated the CA. We confirmed that high glucose, insulin, and palmitic acid cancer could elicit CA in the HCT16 colon cancer cells and found that the experimental treatment increased the binding between NPM and H2B, but not between p-NPM and H2B. The molecular docking analysis supported the fact that NPM and H2B could bind to each other through various amino acid residues. The treatment also increased the colocalization of NPM and H2B in the cytosol. Importantly, disruption of the NPM1-H2B complex by individual knockdown of the protein level of NPM or H2B led to the inhibition of the treatment-evoked CA. In conclusion, our results suggest that the binding between NPM and H2B proteins signals for the CA by high glucose, insulin, and palmitic acid.

[Interpretation of the expert consensus on the whole-process management of herpes zoster-associated pain].

Currently, the diagnosis, treatment and management of herpes zoster-associated pain are not well understood in China. The expert consensus on the whole-process management of herpes zoster-associated pain was focused on the standardization of diagnosis and treatment of herpes zoster-associated pain, such as the time definition of clinical stages, the relevant details of analgesic drugs and minimally invasive interventional therapy, and the value of vaccines in pain management. This article gives a detailed interpretation of the associated content in the consensus.

[Prediction of 6-year risk of activities of daily living disability in elderly aged 65 years and older in China].

Objective: To construct an easy-to-use risk prediction tool for 6-year risk of activities of daily living(ADL) disability among Chinese elderly aged 65 and above. Methods: A total of 34 349 elderly aged 65 and above were recruited from the Chinese Longitudinal Healthy Longevity Survey. Demographic characteristics, lifestyle and chronic diseases of the elderly were collected through face-to-face interviews. The functional status of the elderly was evaluated by the instrumental activities of daily living(IADL) scale. The mental health status of the elderly was evaluated by the Mini-Mental State Examination. The height, weight, blood pressure and other information of the subjects were obtained through physical examination and body mass index(BMI) was calculated. The ADL status was evaluated by Katz Scale at baseline and follow-up surveys. Taking ADL status as the dependent variable and the key predictors were selected from Lasso regression as the independent variables, a Cox proportional risk regression model was constructed and visualized by the nomogram tool. Area under the receiver operating characteristic curve(AUC) and calibration curve were used to evaluate the discrimination and calibration of the model. A total of 200 bootstrap resamples were used for internal validation of the model. Sensitivity analysis was used to evaluate the robustness of the model. Results: The M(Q1, Q3) of subjects' age as 86(75, 94) years old, of which 9 774(46.0%) were males. A total of 112 606 person-years were followed up, 4 578 cases of ADL disability occurred and the incidence density was 40.7/1 000 person-years. Cox proportional risk regression model analysis showed that older age, higher BMI, female, hypertension and history of cerebrovascular disease were associated with higher risk of ADL disability [HR(95%CI) were 1.06(1.05-1.06), 1.05(1.04-1.06), 1.17(1.10-1.25),1.07(1.01-1.13) and 1.41(1.23-1.62), respectively.]; Ethnic minorities, walking 1 km continuously, taking public transportation alone and doing housework almost every day were associated with lower risk of ADL disability [HR(95%CI): 0.71(0.62-0.80), 0.72(0.65-0.80), 0.74(0.68-0.82) and 0.69(0.64-0.74), respectively]. The AUC value of the model was 0.853, and the calibration curve showed that the predicted probability was highly consistent with the observed probability. After excluding non-intervening factors(age, sex and ethnicity), the AUC value of the model for predicting the risk of ADL disability was 0.779. The AUC values of 65-74 years old and 75 years old and above were 0.634 and 0.765, respectively. The AUC values of the model based on walking 1 km continuous and taking public transport alone in IADL and the model based on comprehensive score of IADL were 0.853 and 0.851, respectively. Conclusion: The risk prediction model of ADL disability established in this study has good performance and robustness.

[Association between urinary arsenic levels and anemia among older adults in nine longevity areas of China].

Objective: To investigate the association between urinary arsenic levels and anemia among older adults in nine longevity areas of China. Methods: A total of 1 896 subjects aged 65 years and above who participated in the Healthy Aging and Biomarkers Cohort Study (HABCS) in 2017-2018 were included. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information from the subjects. Through physical examination, data including height, weight and blood pressure were determined and body mass index (BMI) was calculated. Blood and urine samples were collected for the detection of hemoglobin (Hb), blood glucose, blood lipids, plasma vitamin B12 and urinary arsenic concentrations. The urinary arsenic levels were divided into four groups according to the quartiles of urinary arsenic concentrations (µg/g creatinine): Q1 (<18.7), Q2 (18.7-34.5), Q3 (34.6-69.5) and Q4(≥69.6). Multivariate logistic regression model and restricted cubic spline fitting logistic regression model were used to analyze the association between urinary arsenic levels and anemia. Results: The age of the 1 896 subjects (M (Q1, Q3)) was 83 (74, 92) years, including 952 females (50.21%), and the concentration of Hb (M (Q1, Q3)) was 135 (124, 147)g/L. The prevalence of anemia was 24.89% (472 cases). The geometric mean and M (Q1, Q3) of urinary arsenic concentrations were 37.5 and 34.6 (18.7, 69.6)µg/g creatinine, respectively. Multivariate logistic regression model analysis showed that after adjusting for age, gender, BMI, education level, smoking and drinking status, residence, economic level, ethnicity, the status of vitamin B12 deficiency, consumption frequency of aquatic products and meat, the prevalence of hypertension, diabetes and dyslipidemia, urinary arsenic levels were positively associated with anemia (Taking group Q1 as a reference, OR (95%CI) values in Q2, Q3 and Q4 groups were 1.73 (1.20-2.50), 2.08 (1.43-3.02) and 1.52 (1.02-2.28), respectively). The results of restricted cubic spline fitting logistic regression analysis showed a non-linear association between urinary arsenic concentrations and anemia (P<0.001). Subgroup analysis showed there was a negative multiplicative interaction between the prevalence of chronic diseases and urinary arsenic levels with OR (95%CI) was 0.55 (0.30-0.99), while no multiplicative interaction was found between age, gender, residence, smoking status, drinking status and urinary arsenic levels (P>0.05). There was a positive association between urinary arsenic levels and anemia in participants who were absence of chronic diseases,male, living in rural, smoking and drinking with OR (95%CI) values of 3.62 (1.30-10.06),2.46 (1.34-4.52), 1.70 (1.03-2.80), 2.21 (1.01-4.82) and 2.79 (1.23-6.33), respectively. Conclusion: There is a positive association between urinary arsenic levels and anemia among older adults in nine longevity areas of China.

[Association of body mass index and waist circumference with frailty among people aged 80 years and older in Chinese].

Objective: To examine the association of body mass index (BMI) and waist circumference (WC) with frailty among oldest-old adults in China. Methods: A total of 7 987 people aged 80 years and older (oldest-old) who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2017-2018 were included. Information on demographic characteristics, behavior pattern, diet, activities of daily living, cognitive function, health status, disease condition were collected by questionnaire and physical examination. Generalized linear mixed model and restricted cubic splines (RCS) were used to analyze the association of BMI and WC with frailty. Results: The mean age of all participants was 91.7 years, and their mean BMI and WC were (21.3±3.5) kg/m2 and (82.9±10.5) cm, respectively. The proportion of male was 42.3% (3 377/7 987), and the proportion of people with frailty was 33.7% (2 664/7 987). After controlling confounding factors, compared with T2 (19.1-22.1 kg/m2) of BMI, the OR (95%CI) of the female T1 (<19.1 kg/m2) and T3 (≥22.2 kg/m2) group was 1.39 (1.17-1.65) and 1.27 (1.07-1.52), respectively. Compared with T2 (77-85 cm) of WC, the OR (95%CI) of female T1 (<77 cm) and T3 (≥86 cm) group was 1.20 (1.01-1.42) and 1.10 (0.93-1.31), respectively. The results of multiple linear regression model with restrictive cubic spline showed that there was a non-linear association of BMI and WC with frailty in female. Conclusion: There is a U-shaped association of BMI and WC with frailty in female participants.

[The impact of different comprehensive treatment models on patients with adenocarcinoma of esophagogastric junction based on propensity score matching: a single center cohort study].

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ2 test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ2 test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ2=6.971, P=0.008) and nCRT group (6.9% (2/29), χ2=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ2=10.881, P=0.001; χ2=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ2=6.740, P=0.009) and nCRT group (31.0% (9/29), χ2=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ2=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ2=4.976, P=0.083) and progression-free survival (χ2=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.

Evaluation of pulmonary ventilation in COVID-19 patients using oxygen-enhanced three-dimensional ultrashort echo time MRI: a preliminary study.

AIM: To evaluate the lung function of coronavirus disease 2019 (COVID-19) patients using oxygen-enhanced (OE) ultrashort echo time (UTE) MRI. MATERIALS AND METHODS: Forty-nine patients with COVID-19 were included in the study. The OE-MRI was based on a respiratory-gated three-dimensional (3D) radial UTE sequence. For each patient, the percent signal enhancement (PSE) map was calculated using the expression PSE = (S100% - S21%)/S21%, where S21% and S100% are signals acquired during room air and 100% oxygen inhalation, respectively. Agreement of lesion detectability between UTE-MRI and computed tomography (CT) was performed using the kappa test. The Mann-Whitney U-test was used to evaluate the difference in the mean PSE between mild-type COVID-19 and common-type COVID-19. Spearman's test was used to assess the relationship between lesion mean PSE and lesion size. Furthermore, the Mann-Whitney U-test was used to evaluate the difference in region of interest (ROI) mean PSE between normal pulmonary parenchyma and lesions. The Kruskal-Wallis test was applied to test the difference in the mean PSE between different lesion types. RESULTS: CT and UTE-MRI reached good agreement in lesion detectability. Ventilation measures in mild-type patients (5.3 ± 5.5%) were significantly different from those in common-type patients (3 ± 3.9%). Besides, there was no significant correlation between lesion mean PSE and lesion size. The mean PSE of COVID-19 lesions (3.2 ± 4.9%) was significantly lower than that of the pulmonary parenchyma (5.4 ± 3.9%). No significant difference was found among different lesion types. CONCLUSION: OE-UTE-MRI could serve as a promising method for the assessment of lung function or treatment management of COVID-19 patients.

[Clinical features of patients with retinocytoma].

Objective: To analyze the clinical features and fundus performance of patients with retinocytoma. Methods: Retrospective case series study. Ten patients (12 eyes) diagnosed with retinocytoma were enrolled in Department of Ophthalmology of Eye & ENT Hospital of Fudan University from January 2006 to December 2019. Clinical data were reviewed, including gender, age, initial symptoms, tumor size and location, fundus manifestations and regression patterns. Results: There were 7 males and 3 females aged from 5 to 39 years, with a median age of 14 years. Eight patients had unilateral retinocytoma, while 2 patients had bilateral retinocytoma. The most common complaints were strabismus (4 patients) and blurred vision (3 patients). The average maximum base diameter of the tumor was 5.70 mm (2.69 to 8.69 mm), and the average thickness was 2.28 mm (0.61 to 3.76 mm). Tumors in 12 eyes were all of a single focus, 5 in the posterior pole, 5 in the midperiphery and 2 in the periphery. Ophthalmoscopic features of retinocytoma included a translucent retinal mass in 10 eyes, a calcification mass in 11 eyes, with well-defined retinal pigment epithelial alteration in 12 eyes and a zone of chorioretinal atrophy in 6 eyes. The regression patterns were type 1 in 2 eyes, type 2 in 1 eye and type 3 in 9 eyes. The gene test showed RB1 mutation in 1 patient. During the average follow-up of 28.7 months, all of the tumors were stable without malignant transformation. Conclusions: Retinocytoma is a rare benign retinal tumor with characteristic fundus manifestations. Patients with retinocytoma should be monitored closely. (Chin J Ophthalmol, 2021, 57: 526-530).

Biosynthesis of poly-γ-glutamic acid in Escherichia coli by heterologous expression of pgsBCAE operon from Bacillus.

AIMS: Poly-γ-glutamic acid (γ-PGA) is an excellent water-soluble biosynthesis material. To confirm the rate-limiting steps of γ-PGA biosynthesis pathway, we introduced a heterologous Bacillus strain pathway and employed an enzyme-modulated dismemberment strategy in Escherichia coli. METHODS AND RESULTS: In this study, we heterologously introduced the γ-PGA biosynthesis pathway of two laboratory-preserved strains-Bacillus amyloliquefaciens FZB42 and Bacillus subtilis 168 into E. coli, and compared their γ-PGA production levels. Next, by changing the plasmid copy numbers and supplying sodium glutamate, we explored the effects of gene expression levels and concentrations of the substrate l-glutamic acid on γ-PGA production. We finally employed a two-plasmid induction system using an enzyme-modulated dismemberment of pgsBCAE operon to confirm the rate-limiting genes of the γ-PGA biosynthesis pathway. CONCLUSION: Through heterologously over-expressing the genes of the γ-PGA biosynthesis pathway and exploring gene expression levels, we produced 0·77 g l-1 γ-PGA in strain RSF-EBCAE(BS). We also confirmed that the rate-limiting genes of the γ-PGA biosynthesis pathway were pgsB and pgsC. SIGNIFICANCE AND IMPACT OF THE STUDY: This work is beneficial to increase γ-PGA production and study the mechanism of γ-PGA biosynthesis enzymes.

Measurement of cytokines and chemokines and association with clinical severity of dermatomyositis and clinically amyopathic dermatomyositis.

BACKGROUND: Dermatomyositis (DM) is an autoimmune disease affecting primarily the skin, muscle and lung. Dysregulations of cytokines and chemokines are commonly found in inflammatory disorders. OBJECTIVES: To investigate the association between serum cytokines and chemokines and clinical severity, especially cutaneous lesions and interstitial lung disease (ILD) in patients with DM and clinically amyopathic DM (CADM). METHODS: Clinical features, laboratory findings and serum of 40 patients with DM or CADM were collected and analysed. Serum cytokines and chemokines were measured by enzyme-linked immunosorbent assay or cytometric bead array. A multiple unpaired t-test was performed to compare cytokines and chemokines in patients with DM and healthy controls. Correlations of serum cytokines and chemokines with disease severity were evaluated by Spearman's rank correlation test. RESULTS: Serum interferon (IFN)-ß [rs  = 0·37, 95% confidence interval (CI) 0·078-0·62; P = 0·019] and CXCL10 (rs  = 0·32, 95% CI to -0·004 to 0·57; P = 0·045) were significantly correlated with the Cutaneous Dermatomyositis Disease Area and Severity Index activity score in the subset of patients with DM or CADM. Serum levels of interleukin (IL)-6, IL-10, IL-18 and IFN-ß were significantly higher in the patients with acute/subacute interstitial pneumonia (A/SIP) than in the subset without A/SIP (P < 0·05). IL-6 (rs  = 0·54, 95% CI 0·27-0·72; P < 0·001) and IL-18 (rs  = 0·46, 95% CI 0·21-0·65; P = 0·003) were significantly correlated with the serum level of anti-melanoma differentiation-associated protein 5 antibody. CONCLUSIONS: Serum levels of IFN-ß and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM. In addition, serum IL-6, IL-10, IL-18 and IFN-ß were highly correlated with the occurrence of A/SIP. These cytokines may play a role in the pathogenesis of DM and CADM.

[The value of high resolution diffusion weighted imaging in differentiating benign and malignant epithelial tumors of parotid gland].

Objective: To investigate the diagnostic value of RESOLVE DWI in the evaluation of benign and malignant epithelial tumors of parotid gland. Methods: A total of 106 patients in the First Affiliated Hospital of Zhengzhou University with epithelial tumors of parotid gland confirmed by pathology from July 2015 to October 2017 were retrospectively analyzed. All patients underwent preoperative routine MRI and RESOLVE DWI, the ADC average values were calculated, t test were used to compare the ADC values of benign and malignant epithelial tumors of parotid gland. Diagnostic performance of ADC value was compared using receiver operating characteristic (ROC)curves. Results: All lesions were solitary, including 69 benign epithelial tumors and 37 malignant epithelial tumors. The mean ADC values of pleomorphic adenoma and basal cell adenoma, adenolymphoma and malignant epithelial tumors were (1.47±0.16)×10(-3) mm(2)/s, (0.83±0.19)×10(-3) mm(2)/s and(1.14±0.14)×10(-3) mm(2)/s, the mean ADC value of adenolymphoma lower than the rest of the two groups, there were statistically significant differences among them (P<0.05). Using 0.94×10(-3) mm(2)/s≤ADC value≤1.28×10(-3)mm(2)/s as the critical value for diagnosing malignant epithelial tumors of parotid gland and comparing with pathological results, the result obtained had a sensitivity of 81.1%, specificity of 88.9%. ADC value had high correlations compared with pathological results, kappa value was 0.600. Conclusion: RESOLVE DWI can be applied in differential diagnosis between benign and malignant epithelial tumors of parotid gland.

[Short-term efficacy of intravitreal injection of melphalan for refractory vitreous seeding from retinoblastoma].

Objective: To evaluate the efficacy and safety of intravitreal chemotherapy for refractory vitreous seeding from retinoblastoma. Methods: Retrospective series of case studies. Nine patients (13 eyes) with the diagnosis of refractory vitreous seeding were enrolled in Department of Ophthalmology of Eye& ENT Hospital of Fudan University from March 2014 to October 2015.There were 6 males and 3 females. Children aged 8 to 40 months, median age of 18 months. In the 13 eyes, 3 eyes were E period, 9 eyes were D period, and 1 eyes were C period. The fundus was examined by indirect ophthalmoscope and recorded by RetcamIII. Systemic chemotherapy was performed using the VEC protocol, that is vincristine, etoposide, and carboplatin. Local treatment also involves cryotherapy and/or thermotherapy. All patients were treated with intravitreal injection of melphalan. They underwent intravitreal melphalan, once every 4 weeks, with an average of 3 times of injections. The treatment dose of melphalan is 20 to 40 µg per dose. Observe the vitreous seed control and complications of therapy. Results: Vitreous seeds control was attained in all cases. There was no case of orbital extension or remote metastasis. Complications included retinal pigment epithelial and choroidal atrophy in 7 eyes, pupillary synechia and iris atrophy in 2 eyes,retinal vasculitis and vascular occlusion in 2 eyes, optic atrophy in 2 eyes, vitreous hemorrhage in 1 eye, and temporary hypotony in 3 eyes. Conclusions: Intravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma. High dose may lead to local adverse reactions. (Chin J Ophthalmol, 2017, 53: 570-574).

[Eyeball salvage treatment or enucleation for advanced retinoblastoma].

The management of retinoblastoma (RB) has dramatically changed over the past two decades. The introduction of chemotherapy has transformed treatment algorithms completely. Chemotherapy is currently used as a first line approach for children with RB and can be delivered by intravenous, intra-arterial and intravitreal routes. However, there still remains some controversy on the treatment of advanced RB, especially in eyeball salvage. This article described domestic and international approaches to eyeball salvage treatment. We would like to further discuss our opinion on the management of advanced RB based on our clinical experience for attracting more clinical concern on this issue. Many factors should be considered when choosing the appropriate conservative therapy. The choice of eyeball salvage treatment not only depends upon the tumor staging and laterality but also upon compliance and economic factors. Doctors and parents should not blindly pursue eye saving. However, there are still cases where enucleation is definitely the treatment of choice. (Chin J Ophthalmol, 2016, 52: 728-732).

Lithography and doping in strained Si towards atomically precise device fabrication.

We investigate the ability to introduce strain into atomic-scale silicon device fabrication by performing hydrogen lithography and creating electrically active phosphorus δ-doped silicon on strained silicon-on-insulator (sSOI) substrates. Lithographic patterns were obtained by selectively desorbing hydrogen atoms from a H resist layer adsorbed on a clean, atomically flat sSOI(001) surface with a scanning tunnelling microscope tip operating in ultra-high vacuum. The influence of the tip-to-sample bias on the lithographic process was investigated allowing us to pattern feature-sizes from several microns down to 1.3 nm. In parallel we have investigated the impact of strain on the electrical properties of P:Si δ-doped layers. Despite the presence of strain inducing surface variations in the silicon substrate we still achieve high carrier densities (>1.0 × 10(14) cm(-2)) with mobilities of ∼100 cm(2) V(-1) s(-1). These results open up the possibility of a scanning-probe lithography approach to the fabrication of strained atomic-scale devices in silicon.

Geodynamic models of Indian continental flat slab subduction with implications for the topography of the Himalaya-Tibet region.

The slab structure and high elevation of the Himalaya-Tibet region and their underlying mechanisms have been widely discussed. Many studies interpret a flat slab segment of Indian continental lithosphere located below the overriding plate, but interpretations of the northward extent of the flat slab differ substantially, with minimum estimates placing the boundary at the northern margin of the Himalaya (Indus-Yarlung Tsangpo suture), and maximum estimates placing it at the northern boundary of Tibet. In this study, we investigate for the first time if a flat slab segment of subducted buoyant Indian continental lithosphere below the Himalaya-Tibet region is geodynamically feasible and we quantify its northward extent, as well as its contribution to the high topography of the region. We conduct three large-scale fully-dynamic (buoyancy-driven) analogue experiments to simulate the subduction of the Indian continent. Our preferred, and geodynamically most feasible, model shows a continental flat slab extending northward up to ~ 320 km from the Himalayan thrust front, in agreement with recent estimates. Furthermore, it suggests that the positively buoyant flat slab segment of the Indian continent contributes some ~ 1.5-2 km to the high topography of the Himalaya-Southern Tibet region by providing an upward force to elevate the overriding Eurasian plate.

[Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis].

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.