Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.
Ataxia/genetics* ; Child ; Electroencephalography ; Epilepsy/genetics* ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Retrospective Studies ; Spasms, Infantile/genetics*

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

BACKGROUNDThe domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.

METHODSThe study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.

DISCUSSIONThe study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

Background:The increasing prevalence of colorectal cancer (CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment.We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods:We conducted a multicenter,cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014.Each enrolled patient was interviewed using a structured questionnaire.All expenditure data were inflated to the 2014 Chinese Yuan (CNY;1 CNY =0.163 USD).We quantified the overall expenditure and financial burden and by subgroup (hospital type,age at diagnosis,sex,education,occupation,insurance type,household income,clinical stage,pathologic type,and therapeutic regimen).We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results:A total of 2356 patients with a mean age of 57.4 years were included,57.1％ of whom were men;13.9％ of patients had stage Ⅰ cancer;and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY,and the expenditures for stage Ⅰ,Ⅱ,Ⅲll,and Ⅳ disease were 56,099 CNY,59,952 CNY,67,292 CNY,and 82,729 CNY,respectively.Non-medical expenditure accounted for 8.3％ of the overall expenditure.The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY,which accounted for 59.9％ of their previous-year household income and caused 75.0％ of families to suffer an unmanageable financial burden.Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups (P ＜ 0.05),except for sex.Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less (all P ＜ 0.05).Conclusions:For patients in China,direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable.The financial burden varied among subgroups,especially among patients with different clinical stages of disease,which suggests that,in China,CRC screening might be cost-effective.

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

Objective To observe the expression of hypoxia-inducible factor 1 α (HIF-1α) in rat brain after hypoxia-ischemia(HI),and to explore the possible mechanism of L-thyroxine (L-T4) on HIF-1α expression.Methods Sixty-four postnatal 7-day Sprague-Dawley rats were randomly divided into 4 groups:the sham operation group,HI group,menstruum-treated group and L-T4-treated group.HIBD models were generated according to Rice model method.The rats in menstruum-treated group and L-T4-treated group were respectively administrated of intraperitoneal injection of menstruum with the equal volume and 2 μg/100g L-T4,once a day,for 5 days.The expressions of HIF-1α and phospho-protein kinase B(p-Akt) protein were detected by means of immunohistochemistry.Reverse transcription-polymerase chain reaction was used to detect the level of HIF-1α mRNA.Results The levels of p-Akt protein(50.168 ±4.259),HIF-1α protein (72.795 ±6.121) and HIF-1α mRNA (0.448 ± 0.035) were upregulated compared with those in the sham operation group (8.080 ±0.369,38.581 ± 2.846,0.174 ± 0.015),and the differences were significant (all P ＜ 0.05).The levels of p-Akt protein (82.765 ± 6.271),HIF-1 α protein (117.350 ± 9.374) and HIF-1 α mRNA (0.618 ± 0.042) in L-T4-treated group were higher than those in HI group,and the differences were significant (all P ＜ 0.05).The level of HIF-1 α protein was positively correlated with p-Akt protein in HI group and L-T4-treated group [r(HI) =0.635,P=0.048;r(L-T4) =0.694,P=0.026].Conclusions L-T4 can upregulate HIF-1α mRNA and protein expression in neonatal rats with hypoxia-ischemia brain damage.Phosphatidylinositol-3-kinase/protein kinase B signaling pathway may be involved in L-T4 upregulating HIF-1α mRNA and protein expression.

OBJECTIVETo study the urodynamic changes in patients with recent non-infective voiding dysfunction following radical hysterectomy and assess its significance.

METHODSNinety-six patients with cervical cancer, who were not found any abnormal representation of urodynamics before the operation, were selected into this study group. Eighty-three patients in the study group without urinary infection were detected by urodynamic examination following radical hysterectomy, in order to analyze the urodynamic reasons for the non-infective voiding dysfunction following the surgery.

RESULTSForty-two patients were found with non-infective voiding dysfunction after the operation. Low compliance bladder, bladder destrusor dysfunction and destrusor overactivity were the three leading types of postoperative bladder dysfunction. Moreover, the incidences of low compliance bladder (50.0% vs. 17.1%), bladder destrusor dysfunction (58.4% vs. 14.6%) and destrusor overactivity (31.0% vs. 4.9%) in the group with voiding dysfunction were significantly higher than the corresponding values in the group without voiding dysfunction (P < 0.01). Secondarily, forty-two patients with recent non-infective voiding dysfunction were divided into simple irritation sign group, simple obstruction sign group and mixed sign group according to their main symptoms. The incidence of bladder destrusor dysfunction in the simple obstruction sign group was significant higher than that in the simple irritation sign group, and the incidence of detrusor overactivity in the simple irritation sign group was significant higher than that in the other two groups (P < 0.05).

CONCLUSIONSThere were many different types of urodynamic disorder in the patients with recent non-infective voiding dysfunction after radical hysterectomy. Low compliance bladder, bladder destrusor dysfunction and detrusor overactivity caused by the damage of the pelvic autonomic nerve during the operation may be the main reasons for the recent non-infective voiding dusfunction after radical hysterectomy. Moreover, bladder destrusor dysfunction and detrusor overactivity may be the key points for the symptoms of bladder irritation and bladder obstruction. Urodynamic study is important for the etiology analysis and clinical treatment of recent non-infective voiding dysfunction postoperation.

Adult ; Female ; Humans ; Hysterectomy ; adverse effects ; methods ; Middle Aged ; Urinary Bladder ; physiopathology ; Urinary Bladder, Overactive ; etiology ; physiopathology ; Urination Disorders ; etiology ; physiopathology ; Urodynamics ; Uterine Cervical Neoplasms ; physiopathology ; surgery

OBJECTIVETo study the role of N-methyl-D-aspartate-receptor (NMDAR) expression in the development of hearing damage in neonatal rats with hyperbilirubinemia.

METHODSSixty seven-day-old Sprague-Dawley rats were randomly injected with bilirubin of 100 microg/g (low-dose treatment group) or 200 microg/g (high-dose treatment group) or normal saline (control group). Auditory brainstem response (ABR) was examined. The concentrations of bilirubin in blood and brain were measured. NMDAR expression in the cochlear nucleus slices was examined by immunohistochemistry assay.

RESULTSABR reflecting threshold obviously increased, and I, II and III wave latency as well as I-II, II-III and I-III interval were more prolonged in the two bilirubin treatment groups when compared with the control group. The NMDAR expression in the cochlear nucleuse in the two bilirubin treatment groups was obviously lower than that in the control group. The NMDAR expression in the cochlear nucleuse was negatively correlated with the brain bilirubin content and the ABR reflecting threshold in the two bilirubin treatment groups.

CONCLUSIONSAn increased NMDAR activity may play an important role in hearing damage following hyperbilirubinemia.

Animals ; Animals, Newborn ; Bilirubin ; analysis ; Cochlear Nucleus ; chemistry ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Disorders ; etiology ; Hyperbilirubinemia ; complications ; metabolism ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; analysis

OBJECTIVETo construct a three plasmids lentiviral vector containing canine coagulation factor IX (cFIX) gene with ubiquinone promoter (PUB) and observe the expression of cFIX gene.

METHODSLentivirus was generated by transient three-plasmid transfection, namely, the VSV-G envelope expression cassette, the delta NRF packaging plasmid and the PTK 164 plasmid. Viral particles were used to infect the target cell, third passage mesenchymal stem cells (MSCs) and 293T cell respectively at MOI 3: 1. The cFIX activity was detected in cultured cells with one-stage clotting assay.

RESULTSThe MSCs were obtained in vitro. The lentivirus infected MSCs and 293T cells all expressed the active factor IX with the activity of (26.30 +/- 2.10)% and (19.70 +/- 1.53)%, respectively, which are significantly higher than that of control (1.00 +/- 0.05)%.

CONCLUSIONSThe lentiviral vector of three plasmids with ubiquinone promoter (PUB) was constructed and can transfect the MSCs and 293T cells.

Animals ; Bone Marrow Cells ; metabolism ; Cells, Cultured ; Dogs ; Factor IX ; genetics ; metabolism ; Genetic Vectors ; Hemophilia B ; genetics ; metabolism ; Humans ; Lentivirus ; genetics ; Plasmids ; genetics ; Transfection

Bilirubin ; blood ; Child Development ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Neuropsychological Tests