Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.

Aim To investigate the effects of total flavonoids from Rosa rugosa (TFR) on cerebral ischemia reperfusion injury (CIRI) in rats, and to investigate whether TFR inhibited neuronal apoptosis by regulating phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and endoplasmic reticulum stress (ERS) pathways. Methods SD rats were randomly divided into sham operation group, model group, low-dose group (50 mg · kg

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.
Humans ; Pregnancy ; Female ; Hypertension, Pregnancy-Induced/diagnosis* ; Retrospective Studies ; Pre-Eclampsia/epidemiology* ; Risk Factors ; Incidence

AIM: To evaluate the bioequivalence of the test and reference formulations of mycophenolate mofetil capsule in Chinese healthy male subjects under fasting and fed conditions. METHODS: This was a 2-treatment, 2-sequence, 4-period, fully replicated crossover study that included 80 Chinese healthy male subjects (40 subjects in the fasting group and 40 subjects in the fed group, respectively). Subjects were assigned to receive a single oral administration of the test or reference formulation at a dose of 0.25 g in each period. The plasma concentration of mycophenolate mofetil (MMF) and metabolite mycophenolic acid (MPA) were analyhed by LC-MS/MS. The major pharmacokinetic parameters of MMF and MPA were calculated using non-compartmental analysis by WinNonlin 8.0. The statistical analysis was performed by SAS 9.4. Average bioequivalence (ABE) analysis was applied where it has been demonstrated that the within-subject standard deviation of the reference formulation (S

ObjectiveTo explore the relationship between marital status and the prevalence of mild cognitive impairment （MCI） and dementia in the community dwelling old adults， so as to provide sociological data basis for the prevention and control of cognitive impairment. MethodsPeople aged 65 and above in urban and rural areas of Hubei Province were selected by cluster random sampling， and face-to-face interviews were conducted in community health service centers to complete general investigation and neuropsychological evaluation， as well as clinical physical examination and laboratory examination. The diagnostic expert panels， including two neuroscientists and two neuropsychologists with specialized knowledge of dementia， diagnosed MCI and dementia according to Petersen's MCI standard and Chinese Diagnostic guidelines for dementia and Cognitive impairment. Multivariate Logistic regression was used to analyze the correlation between marital status and MCI and dementia in different age groups. ResultsDuring 2018~2020， 8 221 people completed the full neurocognitive assessment and clinical physical examination， with an average age of （71.96±5.895） years， and 1 953 people， accounting for 23.75% of the total number， were without spouses. The crude prevalence of MCI and dementia in HMACS were 25.98%， 95%CI （24.99%， 26.98%） and 7.24%， 95%CI （6.68%，7.80%）， respectively in total participants. After standardization for age and sex using data from the 2010 population census in Hubei Province， the prevalence of MCI and dementia were 26.28% and 6.98%.The prevalence of MCI and dementia in non-spouse ［28.07%， 95%CI （26.08%， 30.06%）；12.45%， 95%CI （10.99%， 13.91%）］ was significantly higher than that in spouse ［22.85%， 95%CI（21.81%， 23.89%； 5.62%， 95%CI （5.05%， 6.19%）］. Multivariable logistic regression model showed that the rates of MCI and dementia for married men aged 65~69 ［P=0.028， OR=0.639，95%CI（0.429， 0.952）］ and above 80 years ［P=0.004，OR=0.460， 95%CI （0.269， 0.785）］ were significantly lower than those of widowed men. However， there was no statistical difference between the presence or absence of spouses and the prevalence of MCI and dementia in older women. ConclusionsThe prevalence of MCI and dementia is higher in older adults without spouses. Especially for men aged 65~69 and 80 and above， having spouses is important to protect cognitive function.

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Child ; Factor VIII/therapeutic use* ; Hemarthrosis ; Hemophilia A/drug therapy* ; Hemorrhage ; Humans ; Retrospective Studies

BACKGROUNDRepetitive transcranial magnetic stimulation (rTMS) and event-related potentials (ERPs) are a noninvasive technique that widely used in neurophysiological field. Although rTMS has shown clinical utility for a number of neurological conditions, Recently,there was little understanding of the the efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and after rTMS treatment. The objective of this study was to investigate the characteristics of N400, mismatch negativity (MMN), and P300 before and after treatment with rTMS in SZ.

METHODSOne hundred and twenty-seven SZ patients hospitalized in Shanghai Mental Health Center from March 2015 to July 2017, divided into two groups (85 patients were recruited as rTMS group and 42 were recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the staff and refresher staff in our hospital were recruited at the same time. A Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After rTMS treatment, N400, P300, and MMN characteristics were compared with those before treatment and NC group.

RESULTSCompared with NC, the SZ patients exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400 amplitudes in the frontal area (elicited by idioms with same phonic and different shape and meaning and with different phonic, shape, and meaning) were increased in the SZ patients (P < 0.05). However, there was no significant change in N400 before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for MMN and target P300 also increased in SZ patients after rTMS treatment (P < 0.05).

CONCLUSIONSBased on our preliminary findings, we believe that the combined usage of N400, MMN, and P300 could be a valuable index and an electrophysiological reference in evaluating the effects of rTMS treatment in SZ patients.

BackgroundRisperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.

MethodsNinety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.

ResultsA total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.

ConclusionsBoth risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.

Antipsychotic Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; drug effects ; China ; Electroencephalography ; Evoked Potentials ; drug effects ; Female ; Humans ; Male ; Paliperidone Palmitate ; pharmacology ; Risperidone ; pharmacology ; Schizophrenia ; drug therapy

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ²=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ²=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ²=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ²=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ²=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ²=0.230, P=0.891; χ²=2.628, P=0.269; χ²=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ²=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.
Adolescent ; Anemia, Aplastic/therapy* ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Retrospective Studies ; Treatment Outcome ; Unrelated Donors