ObjectiveTo assess the feasibility and efficacy of a docetaxel plus cisplatin regimen for patients of locally advanced nasopharyngeal carcinoma(NPC)treated concurrently with definitive IMRT in a short-term observation.MethodsRadiation consisted of 7000 cGy given to the planning target volume (PTV) of primary tumor, 6600 cGy given to the PTV of metastatic lymph nodes and 6000 cGy to the PTV of subclinical disease in 220-228 cGy/fraction were delivered over 31-32 treatment days. Thirty-two patients with newly diagnosed NPC received definitive intensity-modulated radiation therapy(IMRT)concurrent with docetaxel 75 mg/m2 on day 1 and DDP 75 mg/m2 on day 1(or DDP 25 mg/m2 on day 1-day 3), repeating every 21 to 28 days for 2 cycles.ResultsAll patients received the full dose of radiotherapy and completed 2 cycles of chemotherapy with a median follow-up of 13 months (2-28 months).No treatment-related death was observed. Major toxicities included hematologic toxicity and mucositis. The incidence rates of grade 3-4 leucopenia,grade 3-4 neutropenia and grade 3 acute mucositis were 46.9 ％ (15/32),59.4 ％ (19/32) and 40.6 ％ (13/32) respectively.The complete remission (CR) rate was 96.9 ％ (31/32).During treatment,90.6 ％ (29/32)patients acquired granulocyte colony stimulating factor (G-CSF)for leucopenia. The 1-year overall survival, local recurrence-free survival, regional recurrence-free survival and distant metastasis-free survival were 100 ％ (31/32),96.9 ％ (31/32),96.9 ％ (31/32),96.9 ％ (31/32),respectively,for the whole cohort.Conclusions2 cycles of the docetaxel plus cisplatin regimen with concurrent IMRT are demonstrated being feasible and effective in treating locally advanced NPC with promising results.The major toxicities are leucopenia and neutropenia, but they are tolerable with the use of G-CSF. Further investigation of long-term efficacy of the regimen is required.

PurposeIt is well known hypobaric hypoxia occurs with acute exposure to high altitude, with commonly associated change of cerebral blood flow (CBF). In this work, three-dimensional arterial spin-labeling (3D ASL) was used to monitor the change of CBF to further extend our understanding of hypobaric hypoxia.Materials and Methods Six healthy subjects were recruited for this study, they were asked to stay at high altitude areas for 5 days, and then returned to the plain. All subjects received MRI examination in both plain and high altitude areas using exactly the same 3.0T MR scanner. A total of 8 MR scans were performed, and all the parameters were kept the same, the changes of cerebral blood flow were observed.ResultsCBF increased obviously and reached its peak after acute exposure to high altitude, at the first day at high altitude, CBF measurements in global brain, grey matter and white matter increased signiifcantly compared to the plain, the difference was statistically significant (P<0.05); after that, the CBF measurements started to gradually decrease in the second day and a small climb on the third day at high altitude, then the CBF continued to drop after returning to sea level, even below that at sea level prior to departure. After 1 week back to the plain area, CBF measurements in global brain, grey matter and white matter were still lower than those before departure for high altitude areas, with a statistically signiifcant difference (P<0.05).ConclusionCBF measurements had obvious increase upon initial arrival at high altitude, and then the CBF continued to drop even below that at sea level prior to departure.

Objective To investigate whether pantoprazole (PPZ), a proton pump inhibitor,could reverse the transmember pH gradient by inhibiting vacuolar H+-ATPase so as to increase the sensitivity of human gastric adenocarcinoma cell line SGC7901 to antitumor drugs and to evaluate the optimal time of drug administration, dosage of PPZ and the possible mechanism. Methods Western blotting and immunofluorescent staining were used to determine the expression and intracellular distribution of vacuolar H+-ATPase in human gastric adenocarcinoma cell line SGC7901 with or without PPZ pretreatment. 2', 7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF-AM) fluorescent probe was used to measure the intracellular pH value of human gastric adenocarcinoma cell line SGC7901 which pretreated with different dose and time of PPI. Methyl thiazolyl tetrazolium (MTT) assay and annexin V-fluorescent isothiocyanate-propidium iodide double staining were performed to evaluate the cytotoxic effects and apoptosis of cells treated with antitumor drugs combined with PPZ. Adriamycin (ADR) was used as probe to estimate drug accumulation and retention with PPZ pretreatment. Results After 24 hours, the expression of vacuolar H+-ATPase in cells pretreated with PPZ of 10 μg/ml (1.19±0.03) or 100 μg/ml (0. 70±0.03) was significantly lower than that in blank control (1.53±0. 05), but this expression was increased by pretreatment with PPZ of 1 μg/ml (2.29 +0.06, P<0.05). The inhibitory effects of PPZ (10 μg/ml) on vacuolar H+-ATPase was observed at 6 hours (0.32±0.02)and 12 hours (0. 13±0.02). And it could alter the intracellular distribution of vacuolar H+-ATPase at 24-hours. The intracellular pH value in cells pretreated with PPZ of 10 μg/ml (7.44±0. 09 ) or 100 μg/ml (7.31 ± 0. 06) was significantly decreased in comparison with untreated cells (7.51±0.05, P< 0. 01). After administration of anti-tumor drugs, the viability in SGC7901 cells pretreated with PPZ for 24 hours (58.71%±1.18 %) was significantly lower than that in cells untreated with PPZ (74. 33% ± 1.77%, P<0.05), while thetotal and early apoptotic rates in former cells(80.81% ±1. 16% and 77.52 %±1.13 %, respectively) were significantly higher than those in later cells (26. 42%±1.19% and 23. 18% ±0.92%,respectively,P < 0. 01). And the ADR releasing index in cells treated with PPZ (20, 50 and 100 μg/ml) for 24 hours was obviously lower than that in the blank control (0. 164±0. 013, 0. 162±0.015, 0. 152±0. 012 vs 0. 277±0. 011, respectively, P<0. 01). Conclusion The sensitivity of human gastric adenocarcinoma cell line to antitumor drugs may be increased by pretreatment with PPZ.

Objective To investigate plasma level of soluble intercellular adhesion molecule-1 (sICAM-1)and soluble E-slectin (sES) in patients with Keshan disease (KD) accompanied by hypertension,and to further their relation to systolic blood pressure (SBP),diastolic blood pressure (DBP) and ejection fraction (EF) of left ventricle.Methods Patients with Keshan disease investigated in 2007 in Fuyu County,Heilongjiang Province were divided into two groups according to whether they were accompanied by hypertension or not:KDP group (n =17),the patients were diagnosed as Keshan disease accompanied by hypertension;KDN group (n =14),the patients were only diagnosed as Keshan disease.Healthy volunteers lived in the same area as the patients were included in the control group (CON group,n =10).The clinical data (such as age,sex and past medical history),SBP and DBP were recorded.EF was detected by echocardiography.Plasma sICAM-1 and sES concentrations were measured by ABC-enzyme-linked immunosorbent assay technique.Results Plasma level of sICAM-1 in the subjects was significantly elevated in KDP group as compared with that in CON group and KDN group [(399.84 ± 99.06) vs (323.06 ± 61.27) μg/L,P ＜0.05;(399.84 ± 99.06) vs (268.27 ± 72.88) μg/L,P ＜ 0.01].However,there was no statistical significance in plasma sICAM-1 between the KDN group and control group (P ＞ 0.05).The difference of plasma sES between the control group,KDN group and KDP group did not reach statistical significance [(76.31 ± 23.17),(72.26 ± 20.15) and (90.21 ± 19.21) μg/L,F =3.236,P ＞ 0.05].As compared with the KDN group,SBP and DBP were obviously higher in KDP group [(169 ± 27) and (121 ± 10) mmHg,(102 ± 17) and (81 ± 6) mmHg,1 mmHg =0.133 kPa,F =6.376,4.300,all P ＜ 0.01],and EF was not significantly increased [(58 ± 14)％ and (55 ± 14)％,F =0.789,P ＞ 0.05].Furthermore,correlation analysis showed plasma sICAM-1 was positively correlated with SBP (r =0.540 6,P ＜ 0.01)and DBP (r =0.461 2,P ＜ 0.01),but not with EF of left ventricle in subjects whir Keshan disease (r =0.073 4,P ＞0.05).Conclusion These data shows slCAM-1 may play a role in the development of Keshan disease accompanied by hypertension,providing an potential index for its risk assessment.

In order to evaluate the efficacy and side effects of the non-insulin antidiabetes medications as an adjunct treatment in type 1 diabetes mellitus (T1DM), we conducted systematic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between the date of inception and March 2020 to produce a systematic review and meta-analysis. Overall, 57 studies were included. Compared with placebo, antidiabetes agents in adjunct to insulin treatment resulted in significant reduction in glycosylated hemoglobin (weighted mean difference [WMD], –0.30%; 95% confidence interval [CI], –0.34 to –0.25%; P<0.01) and body weight (WMD, –2.15 kg; 95% CI, –2.77 to –1.53 kg; P<0.01), and required a significantly lower dosage of insulin (WMD, –5.17 unit/day; 95% CI, –6.77 to –3.57 unit/day; P<0.01). Compared with placebo, antidiabetes agents in adjunct to insulin treatment increased the risk of hypoglycemia (relative risk [RR], 1.04; 95% CI, 1.01 to 1.08; P=0.02) and gastrointestinal side effects (RR, 1.99; 95% CI, 1.61 to 2.46; P<0.01) in patients with T1DM. Compared with placebo, the use of non-insulin antidiabetes agents in addition to insulin could lead to glycemic improvement, weight control and lower insulin dosage, while they might be associated with increased risks of hypoglycemia and gastrointestinal side effects in patients with T1DM.

In order to evaluate the efficacy and side effects of the non-insulin antidiabetes medications as an adjunct treatment in type 1 diabetes mellitus (T1DM), we conducted systematic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between the date of inception and March 2020 to produce a systematic review and meta-analysis. Overall, 57 studies were included. Compared with placebo, antidiabetes agents in adjunct to insulin treatment resulted in significant reduction in glycosylated hemoglobin (weighted mean difference [WMD], –0.30%; 95% confidence interval [CI], –0.34 to –0.25%; P<0.01) and body weight (WMD, –2.15 kg; 95% CI, –2.77 to –1.53 kg; P<0.01), and required a significantly lower dosage of insulin (WMD, –5.17 unit/day; 95% CI, –6.77 to –3.57 unit/day; P<0.01). Compared with placebo, antidiabetes agents in adjunct to insulin treatment increased the risk of hypoglycemia (relative risk [RR], 1.04; 95% CI, 1.01 to 1.08; P=0.02) and gastrointestinal side effects (RR, 1.99; 95% CI, 1.61 to 2.46; P<0.01) in patients with T1DM. Compared with placebo, the use of non-insulin antidiabetes agents in addition to insulin could lead to glycemic improvement, weight control and lower insulin dosage, while they might be associated with increased risks of hypoglycemia and gastrointestinal side effects in patients with T1DM.

Objective: To investigate the epidemiologic characteristics of Norovirus among adult patients suffering from infectious diarrhea in Shanghai, so as to provide evidence for developing related strategies on prevention and control of the disease. Methods: Diarrheal outpatients were monitored at the 'Intestinal clinic’ from 22 hospitals involved in the sentinel surveillance program in Shanghai. Information on demographic and epidemiologic features of the patients was collected while data and clinical, fecal specimens were collected and sent to the district CDC for Norovirus detection. Positive rates of Norovirus were also compared in various populations and seasons during 2013-2018. Multivariate logistic regression model was adopted to fit into the comparisons between non-Norovirus and Norovirus groups. Results: 19.28% of the 12 083 diarrheal cases were found to have carried the Norovirus, with GⅡgroup the most commonly identified genotype. Rates of detection was seen higher in males (20.78%) than in females (17.73%). 30-44 year-old were found having the highest positive rate (21.51%). The positive rates were found the highest (23.60%) in the year of 2015. All the above shown differences were statistically significant (P<0.05). Diarrheal patients affected with Norovirus would present watery stool (75.94%) and vomiting (35.84%). Data from the multivariate logistic analysis showed that factors as: being males, 30-44 years old, officials/clerks, in winter season and with histories of travelling etc., were related to higher risks on Norovirus infection. Conclusions Infectious diarrhea caused by Norovirus occurred all year round, with seasonal peaks seen in winter and spring, in Shanghai. Specific prevention and control measures should be taken on Norovirus- caused infectious diarrhea, according to the difference on age, gender and season.

Objective: To evaluate the effectiveness of varicella vaccine in varicella outbreaks and to analyze the influencing factors, and to provide a reference for making the targeted prevention and controlling measures. Methods: A total of 3 888 students with no history of varicella were selected from 2 schools with varicella outbreak in Guangdong Province in 2021, a retrospective cohort study was conducted by using questionnaire survey, rate ratio ( RR ) and vaccine effectiveness ( VE ) values were calculated and Logistic regression was uses to analyze the factors influencing the protective effect of varicella. Results: There were 138 confirmed cases of varicella among the participants. There was no significant sex difference in the vaccination rate( χ 2=1.36, P =0.51), but there was significant difference in the vaccinattion rate of different age groups( χ 2=555.82, P <0.01). The overall protective effect of VarV was 66.94%(95% CI =56.17%-77.71%), and the protective effect of 2 doses of vaccine( VE = 90.02% , 95% CI =83.13%-96.90%) was higher than that of 1 dose( VE =49.40%, 95% CI =32.36%-66.44%)( χ 2=24.93, P < 0.01 ). The high fever rates in the vaccinated and unvaccinated groups were 7.69% and 25.81%, with significant difference( χ 2= 6.29 , P <0.05). The rates of moderate and severe skin lesions of vaccinated and unvaccinated groups was 20.00% and 50.00%, respectively, and the difference was statistically significant( χ 2=11.32, P <0.01). The protective effects of varicella vaccine against high fever and moderate to severe rash were 70.19%(95% CI =42.11%-98.27%) and 60.00%(95% CI =38.15%-81.85%). Stratified analysis showed that there were significant differences in different years of vaccination( χ 2=37.87, P <0.05), while there were no significant differences in age of vaccination and vaccine manufacturer ( P >0.05). Conclusion Varicella vaccination can prevent chickenpox infection and reduce the severity of the disease. However, the efficacy of varicella vaccine was affected by vaccination years. It is recommended to improve the vaccination coverage of varicella vaccine to prevent the outbreak of the epidemic.

Objective:To investigate the relationship between serum 25 hydroxyvitamin-D3, soluble advanced glycation end product receptor (sRAGE), nucleotide binding oligomerization domain like receptor 3 (NLRP3) mRNA and cognitive impairment in hypertensive intracerebral hemorrhage (HICH).Methods:143 patients with HICH treated in the Affiliated Hospital of Guangdong Medical University from July 2016 to July 2019 were selected as the research objects. Among the 143 patients with HICH, there were 68 patients with cognitive impairment (cognitive impairment group) and 75 patients without cognitive impairment (control group). The age, gender, amount of intracerebral hemorrhage, bleeding site, blood pressure, blood glucose and blood lipid of the two groups were counted, and the mRNA levels of 25 hydroxyvitamin-D3, sRAGE and NLRP3 were detected. Multivariate logistic regression analysis was used to analyze the risk factors of cognitive impairment in patients with HICH.Results:There were no significant differences in age, gender, smoking, education, bleeding site, diabetes rate, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) between cognitive dysfunction group and control group ( P>0.05); There were significant differences in bleeding volume and neurological function defect score (NIHSS) score between cognitive impairment group and control group ( P<0.05); The level of 25 hydroxyvitamin-D3 in cognitive impairment group was lower than that in control group ( P<0.05), and the expression level of NLRP3 mRNA was higher than that in control group ( P<0.05). There was no significant difference in sRAGE between the two groups ( P>0.05); Logistic regression analysis showed that the decrease of 25-hydroxyvitamin-D3 level, the increase of bleeding volume and NIHSS score were independent risk factors for cognitive impairment in HICH patients ( P<0.05). Conclusions:Decreased serum 25 hydroxyvitamin-D3 levels may increase the risk of cognitive impairment in patients with HICH.

Objective:To observe the effects of acupuncture and moxibustion on phosphatase and PTEN-induced putative kinase 1(PINK1)/Parkin signaling pathway in the midbrain substantia nigra of Thy1-α synuclein(αSyn)transgenic model mice with Parkinson disease(PD). Methods:Twenty-four Thy1-αSyn transgenic mice were randomly divided into a model group,an acupuncture group,an acupuncture + moxibustion group,and a Western medicine group.Six wild-type mice in the same litter were used as the wild-type group.In the acupuncture group,Baihui(GV20)and Yanglingquan(GB34)were selected for acupuncture.In the acupuncture + moxibustion group,Guanyuan(CV4)was added on the basis of the acupuncture group.The Western medicine group was given rapamycin intraperitoneal injection at a dose of 10 mg/(kg·bw).The wild-type group and the model group were fixed without intervention.The overall rod performance(ORP)score of mice was observed in each group.The immunohistochemical method was used to detect the tyrosine hydroxylase(TH)positive neurons in the substantia nigra of mice in each group.The αSyn was detected by the immunofluorescence chemical method.The expression levels of αSyn,microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,autophagy protein sequestosome-1/protein 62(SQSTM-1/p62),PINK1,Parkin,and ubiquitin-specific protease 30(USP30)proteins were detected by Western blotting assay.The expression levels of LC3B,p62,PINK1,Parkin,and USP30 mRNAs were detected by fluorescence quantitative polymerase chain reaction. Results:Compared with the wild-type group,the ORP score,the p62,PINK1,and Parkin protein expression levels decreased significantly(P<0.01),the PINK1 mRNA expression level decreased(P<0.05),while the protein and mRNA expression levels of USP30 increased(P<0.05)in the model group.Compared with the model group,the ORP score in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the expression level of LC3-Ⅱ/LC3-Ⅰ protein in the acupuncture + moxibustion group and the Western medicine group increased(P<0.05);the protein expression levels of p62,PINK1,and Parkin increased(P<0.05),while the USP30 protein expression level decreased significantly(P<0.01)in the acupuncture group,the acupuncture + moxibustion group,and the Western medicine group;the Parkin mRNA expression level in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the USP30 mRNA expression level in the acupuncture + moxibustion group decreased(P<0.05). Conclusion:Acupuncture and moxibustion regulate the related molecule expression levels of PINK1/Parkin signaling pathway in the Thy1-αSyn transgenic PD model mice and promote the autophagy degradation of αSyn to exert the protective effect of dopaminergic neurons.