Endoplasmic reticulum stress promotes hepatocellular carcinoma by modulating immunity: a study based on artificial neural networks and single-cell sequencing.

INTRODUCTION: Hepatocellular carcinoma (HCC) is characterized by the complex pathogenesis, limited therapeutic methods, and poor prognosis. Endoplasmic reticulum stress (ERS) plays an important role in the development of HCC, therefore, we still need further study of molecular mechanism of HCC and ERS for early diagnosis and promising treatment targets. METHOD: The GEO datasets (GSE25097, GSE62232, and GSE65372) were integrated to identify differentially expressed genes related to HCC (ERSRGs). Random Forest (RF) and Support Vector Machine (SVM) machine learning techniques were applied to screen ERSRGs associated with endoplasmic reticulum stress, and an artificial neural network (ANN) diagnostic prediction model was constructed. The ESTIMATE algorithm was utilized to analyze the correlation between ERSRGs and the immune microenvironment. The potential therapeutic agents for ERSRGs were explored using the Drug Signature Database (DSigDB). The immunological landscape of the ERSRGs central gene PPP1R16A was assessed through single-cell sequencing and cell communication, and its biological function was validated using cytological experiments. RESULTS: An ANN related to the ERS model was constructed based on SRPX, THBS4, CTH, PPP1R16A, CLGN, and THBS1. The area under the curve (AUC) of the model in the training set was 0.979, and the AUC values in three validation sets were 0.958, 0.936, and 0.970, respectively, indicating high reliability and effectiveness. Spearman correlation analysis suggests that the expression levels of ERSRGs are significantly correlated with immune cell infiltration and immune-related pathways, indicating their potential as important targets for immunotherapy. Mometasone was predicted to be the most promising treatment drug based on its highest binding score. Among the six ERSRGs, PPP1R16A had the highest mutation rate, predominantly copy number mutations, which may be the core gene of the ERSRGs model. Single-cell analysis and cell communication indicated that PPP1R16A is predominantly distributed in liver malignant parenchymal cells and may reshape the tumor microenvironment by enhancing macrophage migration inhibitory factor (MIF)/CD74 + CXCR4 signaling pathways. Functional experiments revealed that after siRNA knockdown, the expression of PPP1R16A was downregulated, which inhibited the proliferation, migration, and invasion capabilities of HCCLM3 and Hep3B cells in vitro. CONCLUSION: The consensus of various machine learning algorithms and artificial intelligence neural networks has established a novel predictive model for the diagnosis of liver cancer associated with ERS. This study offers a new direction for the diagnosis and treatment of HCC.

Short-Term Efficacy of Cerebello-spinal tDCS and Body Weight-Supported Treadmill Training in the Hypertrophic Olivary Degeneration: a Rare Case Report.

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

Transcranial Alternating Current Stimulation in a Patient with Ataxia-Ocular Apraxia 2: a Case Report.

Ataxia-ocular apraxia 2 (AOA2) is a rare neurodegenerative autosomal recessive disorder with no effective treatment. In this study, we present the case of a patient diagnosed with AOA2, who experienced walking instability and uncoordinated movement. The patient underwent transcranial alternating current stimulation (tACS) treatment for 4 weeks with follow-up after 1 month. The effectiveness of the treatment was evaluated using the International Cooperative Ataxia Rating Scale (ICARS), the Scale for the Assessment and Rating of Ataxia (SARA), the 9-Hole Peg Test (9HPT), and functional near-infrared spectroscopy (fNIRS). Following treatment, the patient's ataxia symptoms showed significant improvement and continued to be alleviated during the follow-up period, suggesting a lasting effect of tACS treatment. Our findings from this case study provide compelling evidence for the potential of tACS as a treatment option for AOA2.

Widespread of non-typeable Haemophilus influenzae with high genetic diversity after two decades use of Hib vaccine in China.

BACKGROUND: The aim of this study was to analyze the microbiological characteristics of nasopharyngeal carriage Haemophilus influenzae isolates collected from children with respiratory infections in Beijing hospital and Youyang Hospital of China. METHODS: The serotypes of all isolates were determined using latex agglutinated antisera (a-f). The minimum inhibitory concentrations (MICs) of 11 antibiotics were determined using E-test strips. For the beta-lactamase-negative ampicillin-resistant (BLNAR) isolates, ftsI gene was sequenced based on fragments amplified by PCR. STs of H influenzae isolates were determined by multi-locus sequence typing. RESULTS: The overall carriage rate of H influenzae in the study population was 9.1% (362/3984). One hundred and ninety H influenzae isolates which were selected in our study were non-typeable (NTHi) and 44 (23.2%) of them were positive for ß-lactamase. All isolates were susceptible to ceftriaxone and levofloxacin. Susceptibility rates to erythromycin and sulfamethoxazole-trimethoprim in Beijing were significantly higher than Youyang (P < .05). Thirty-six BLNAR isolates were identified. The MLST analysis showed 108 STs in 190 isolates, the most common of which were ST408 (11, 5.8%), ST914 (10, 5.3%), ST57 (9, 4.7%), and ST834 (6, 3.2%). Twelve STs were detected in both of the study sites, which covered 63 isolates. CONCLUSIONS: All isolates in the present study were NTHi, which suggested widespread of this type in China. The BLNAR isolates were detected more frequently than before. Because high genetic diversity of NTHi isolates of H influenzae exists worldwide, it is important to continuously monitor these bacteria in the future.

[Effects of phthalate on pulmonary allergy of offspring during intrauterin and lactating exposure].

OBJECTIVE: To investigate the effects of exposure to diethyl phthalate(DEHP) during pregnancy and lactation in respiratory allergy of offspring Wistar rats. METHODS: To establish the maternal DEHP exposure model: 36 healthy 2-month-old female Wistar rats were divided into three different dose groups. From GD0, each group of pregnant mice were given different concentrations of DEHP(0, 30, 300 mg/(kg·d)) until to the newborn weaning(PND21). After birth, one of offspring was selected from each cage in different dose groups. At PND21 and PND28 the offspring were sensitized by intraperitoneal injection(i. p. ) OVA and continuous nasal sensitization at PND32, PND33, PND34. Bronchoalveolar lavage fluid(BALF) and lung tissue were collected at PND35 with non-sensitized groups. ELISA detected the secretion of Th2 cytokine interleukin(IL)-4, IL-5 and IL-13 in BALF, and the pathological changes of allergic inflammation in lung tissues were observed by HE and PAS staining. Expression of epithelium-derived factor IL-33 detected by immunohistochemistry. RESULTS: In BALF, compared with the control group, the total number of inflammatory cells and eosinophils in the DEHP0+OVA group increased to(131. 500±25. 548)×10~4, (32. 000±10. 079)×10~4(P<0. 05); The total number of inflammatory cells and eosinophils in the DEHP30+OVA group increased to(156. 167±17. 994)×10~4, (16. 331±6. 667)×10~4(P<0. 05); and the total number of inflammatory cells and eosinophils in the DEHP300+OVA group increased to(172. 167±19. 994)×10~4, (55. 000±17. 018)×10~4(P<0. 05). After adding different doses of DEHP and OVA, compared with the control group, The expression levels of IL-4, IL-5, IL-13 in DEHP0+OVA group increased to(38. 401±6. 594) pg/mL(P>0. 05), (30. 026±2. 756) pg/mL(P<0. 05), (13. 806±4. 355) pg/mL(P<0. 05); The expression levels of IL-4, IL-5 and IL-13 in DEHP30+OVA group increased to(57. 733±7. 293) pg/mL(P<0. 05) and(31. 544±1. 043) pg/mL(P>0. 05), (18. 068±1. 497) pg/mL(P<0. 05); The expression levels of IL-4, IL-5 and IL-13 in DEHP300+OVA group increased to(54. 943±6. 049) pg/mL(P>0. 05) and(32. 377±3. 739)pg/mL(P>0. 05), (20. 168±0. 939) pg/mL(P<0. 05), respectively. The tissue section of all the DEHP+saline groups could be observed that no obvious allergic inflammatory reaction, meanwhile all the DEHP+OVA groups had a relatively obvious allergic reaction and were severe with the increase of DEHP dose. Immunohistochemistry showed no significant increase in the expression of IL-33 in the DEHP+saline groups, while the expression of IL-33 in the DEHP+OVA groups increased with a certain dose response. CONCLUSION: Exposure to DEHP during pregnancy and lactation will aggravate the sensitization reaction of offspring, the possible mechanism that DEHP increase the Th2 type of immune response may be the overexpression of IL-33 in the epithelial cells.

ß-Lactamase production and antibiotic susceptibility pattern of Moraxella catarrhalis isolates collected from two county hospitals in China.

BACKGROUND: Moraxella catarrhalis (M. catarrhalis) is an important bacterial pathogen. However, its antibiotic susceptibility patterns in different areas are difficult to compare because of the use of different methods and judgement criteria. This study aimed to determine antimicrobial susceptibility and ß-lactamase activity characteristics of M. catarrhalis isolates collected from two county hospitals in China, and to express the results with reference to three commonly used judgement criteria. RESULTS: Nasopharyngeal swabs were obtained from child inpatients with respiratory tract infections at the People's Hospital of Zhongjiang County and Youyang County from January to December 2015. M. catarrhalis strains were isolated and identified from the swabs, and susceptibility against 11 antimicrobials was determined using the E-test method or disc diffusion. Test results were interpreted with reference to the standards of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), the Clinical and Laboratory Standards Institute (CLSI), and the British Society for Antimicrobial Chemotherapy (BSAC). Detection of ß-lactamase activity was determined by the chromogenic cephalosporin nitrocefin. M. catarrhalis yield rates were 7.12 and 9.58% (Zhongjiang County, 77/1082 cases; Youyang County, 101/1054 cases, respectively). All isolates were susceptible to amoxicillin-clavulanic acid. The susceptibility rate to meropenem was 100% according to EUCAST; no breakpoints were listed in CLSI or BSAC. The non-susceptibility rate to sulfamethoxazole-trimethoprim differed significantly between the two hospitals regardless of the judgemnet criteria used, with isolates from Zhongjiang showing higher susceptibility to those from Youyang (Fisher's exact test, P < 0.05). According to CLSI, the total non-susceptibility rate to erythromycin was 70.8% (Zhongjiang County, 79.2%; Youyang County, 64.3%), and the rate reached 92.1% (Zhongjiang County, 90.9%; Youyang County, 93.1%) on the basis of EUCAST or BSAC. The total positive rate of ß-lactamase was 99.4% (177/178 cases) (Zhongjiang County, 100%, 77/77 cases; Youyang County, 99.0%, 100/101 cases). CONCLUSIONS: Ninety nine percent of M. catarrhalis isolates produce ß-lactamase. The isolates showed poor susceptibility to ampicillin and erythromycin, and high susceptibility to the third- and fourth-generation cephalosporins and amoxicillin-clavulanic. Significant discrepancies between different antimicrobial susceptibility judgemnet criteria were noted.

Optimal combination of feature selection and classification via local hyperplane based learning strategy.

BACKGROUND: Classifying cancers by gene selection is among the most important and challenging procedures in biomedicine. A major challenge is to design an effective method that eliminates irrelevant, redundant, or noisy genes from the classification, while retaining all of the highly discriminative genes. RESULTS: We propose a gene selection method, called local hyperplane-based discriminant analysis (LHDA). LHDA adopts two central ideas. First, it uses a local approximation rather than global measurement; second, it embeds a recently reported classification model, K-Local Hyperplane Distance Nearest Neighbor(HKNN) classifier, into its discriminator. Through classification accuracy-based iterations, LHDA obtains the feature weight vector and finally extracts the optimal feature subset. The performance of the proposed method is evaluated in extensive experiments on synthetic and real microarray benchmark datasets. Eight classical feature selection methods, four classification models and two popular embedded learning schemes, including k-nearest neighbor (KNN), hyperplane k-nearest neighbor (HKNN), Support Vector Machine (SVM) and Random Forest are employed for comparisons. CONCLUSION: The proposed method yielded comparable to or superior performances to seven state-of-the-art models. The nice performance demonstrate the superiority of combining feature weighting with model learning into an unified framework to achieve the two tasks simultaneously.

[Relationship among resilience, coping style and mental health of newly recruited workers born after 1990 in manufacturing industry of Shenzhen City].

OBJECTIVE: To explore the relationship among psychological resilience, coping styles and mental health of newly recruited production line workers who were horn after 1990 in three manufacturing factories in Shenzhen. METHODS: Production line workers who were born after 1990 and started working one week ago were selected from three manufacturing factories in Shenzhen. The Chinese Connor-Davidson Resilience Scale, Simplified Coping Stlye Questionnaire and General Health Questionnaire were used to assess their psychological resilience, psychological pressure, and mental health. A path analysis was carried out by Amos version 17. 0. RESULTS: Significantly positive correlation between the resilience and mental health (P < 0. 01), mental health and psychological resilience were positively related to active coping style (P < 0. 01), mental health and resilience were nagatively related to passive coping style (P < 0. 01). The structural equation model showed that the psychological resilience had both direct and indirect effect on mental health with the mediation effect of active coping styles and passive coping style. CONCLUSION: There are linear relationships between psychological resilience, coping styling and mental healthof the new recruits in Shenzhen manufacturing industry, and the partial indirectly of psychological resilience on mental health is potential realized through active coping styles and passive coping styles.

Case report: Beneficial effects of visual cortex tDCS stimulation combined with visual training in patients with visual field defects.

Background: Visual field defect (VFD) refers to the phenomenon that the eye is unable to see a certain area within the normal range of vision, which may be caused by eye diseases, neurological diseases and other reasons. Transcranial direct current stimulation (tDCS) is expected to be an effective treatment for the recovery or partial recovery of VFD. This paper describes the potential for tDCS in combination with visual retraining strategies to have a positive impact on vision recovery, and the potential for neuroplasticity to play a key role in vision recovery. Methods: This case report includes two patients. Patient 1 was diagnosed with a right occipital hemorrhage and homonymous hemianopia. Patient 2 had multiple facial fractures, a contusion of the right eye, and damage to the optic nerve of the right eye, which was diagnosed as a peripheral nerve injury (optic nerve injury). We administered a series of treatments to two patients, including transcranial direct current stimulation; visual field restoration rehabilitation: paracentric gaze training, upper and lower visual field training, VR rehabilitation, and perceptual training. One time per day, 5 days per week, total 6 weeks. Results: After 6 weeks of visual rehabilitation and tDCS treatment, Patient 1 Humphrey visual field examination showed a significant improvement compared to the initial visit, with a reduction in the extent of visual field defects, increased visual acuity, and improvement in most visual functions. Patient 2 had an expanded visual field, improved visual sensitivity, and substantial improvement in visual function. Conclusion: Our case reports support the feasibility and effectiveness of tDCS combined with visual rehabilitation training in the treatment of occipital stroke and optic nerve injury settings.

Effect of tDCS combined with virtual reality for post-stroke cognitive impairment: a randomized controlled trial study protocol.

BACKGROUND: Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. METHODS: This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects' speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. DISCUSSION: Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

[Analysis of psychological resilience of left-behind high school students in Nanchong rural].

OBJECTIVE: To analyze the scores of psychological resilience of left-behind rural high school students and then provide the basis of mental health supporting for these students. METHODS: survey include multi-stage sampling, extracting a total of 1,000 students of all grades from two rural high schools, and letting them fill the questionnaire "New Resilience & Youth Development Module" within limited time. RESULTS: Contrast between students being left-behind for varying length of time and non-left-behind ones: school factors (36.57 +/- 8.62), internal factors (49.44 +/- 9.89), peer factors (16.78 +/- 3.82) and family factors (22.90 +/- 7.56). Students being left-behind for varying length of time all score lower than non-left-behind ones, and the difference was statistically significant (P < 0.05). Contrast between gender: left-behind high school girls score lower than left-behind high school boys and non-left-behind students in school psychological resilience (34.84 +/- 6.62), and the difference was statistically significant (P < 0.05). Contrast between different types of being left-behind and non-left-behind: parents left-behind vs non-left-behind, and father-left-behind vs non-left-behind-school factors (33.43 +/- 7.43 vs 39.70 +/- 8.12), social factors, internal factors, peer factors and family factors. Students of both types score lower than non-left-behind ones, and the difference was statistically significant (P < 0.05). CONCLUSION: The psychological resilience scores of left-behind high school students are lower than that of non-left-behind students. Therefore, effective measures is necessary to improve the psychological resilience of left-behind rural high school students.

Novel role for non-invasive neuromodulation techniques in central respiratory dysfunction.

Respiration is a crucial steady-state function of human life. Central nervous system injury can damage the central respiratory pattern generator (CRPG) or interrupt its outflow, leading to central respiratory paralysis and dysfunction, which can endanger the patient's life. At present, there is no effective means to reverse this process. Commonly used non-invasive neuromodulation techniques include repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and so forth, which have been widely applied in nervous system diseases and their various secondary symptoms, but rarely in respiratory function. Clinical and animal studies have confirmed that TMS is also suitable for investigating the excitability and plasticity of ascending corticospinal respiratory pathways. In addition, although rTMS and tDCS differ in their respective mechanisms, both can regulate respiratory networks in healthy individuals and in diseased states. In this review, we provide an overview of the physiology of respiration, the use of TMS to assess the excitability of corticophrenic pathways in healthy individuals and in central respiratory disorders, followed by an overview of the animal and clinical studies of rTMS, tDCS and so forth in regulating respiratory circuits and the possible mechanisms behind them. It was found that the supplementary motor area (SMA) and the phrenic motor neuron (PMN) may be key regulatory areas. Finally, the challenges and future research directions of neuroregulation in respiratory function are proposed. Through understanding how neuromodulation affects the respiratory neural circuit non-invasively, we can further explore the therapeutic potential of this neuromodulation strategy, so as to promote the recovery of respiratory function after central nervous system diseases or injury.

Effects of cerebellar transcranial alternating current stimulation in cerebellar ataxia: study protocol for a randomised controlled trial.

Background: Cerebellar ataxia (CA) is a movement disorder that can affect balance and gait, limb movement, oculomotor control, and cognition. Multiple system atrophy-cerebellar type (MSA-C) and spinocerebellar ataxia type 3 (SCA3) are the most common forms of CA, for which no effective treatment is currently available. Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation supposed to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. The cerebellar tACS can modulate the cerebellar outflow and cerebellum-linked behavior and it is a proven safe technique for humans. Therefore, the aim of this study is to 1) examine whether cerebellar tACS improves ataxia severity and various non-motor symptoms in a homogeneous cohort of CA patients consisting of MSA-C and SCA3, 2) explore the time course of these effects, and 3) assess the safety and tolerance of cerebellar tACS in all participants. Methods/design: This is a 2-week, triple-blind, randomised, sham-controlled study. 164 patients (MSA-C: 84, SCA3: 80) will be recruited and randomly assigned to either active cerebellar tACS or sham cerebellar tACS, in a 1:1 ratio. Patients, investigators, and outcome assessors are unaware of treatment allocation. Cerebellar tACS (40 min, 2 mA, ramp-up and down periods of 10s each) will be delivered over 10 sessions, distributed in two groups of five consecutive days with a two-day break in between. Outcomes are assessed after the tenth stimulation (T1), and after 1 month (T2) and 3 months (T3). The primary outcome measure is the difference between the active and sham groups in the proportion of patients with an improvement of 1.5 points in the Scale for the Assessment and Rating of Ataxia (SARA) score after 2 weeks of treatment. In addition, effects on a variety of non-motor symptoms, quality of life, and autonomic nerve dysfunctions are assessed via relative scales. Gait imbalance, dysarthria, and finger dexterity are objectively valued via relative tools. Finally, functional magnetic resonance imaging is performed to explore the possible mechanism of treatment effects. Discussion: The results of this study will inform whether repeated sessions of active cerebellar tACS benefit CA patients and whether this form of non-invasive stimulation might be a novel therapeutic approach to consider in a neuro-rehabilitation setting.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05557786; https://www.clinicaltrials.gov/ct2/show/NCT05557786.

One single-center serological survey on measles, rubella and mumps antibody levels of people in Youyang, China.

Although measles, rubella and mumps elimination had achieved great progress in recent years, outbreaks were still reported worldwide. Serological surveillance on the remaining susceptibility in the population is essential to evaluate the preventive policy, estimate the current risk of infection, and predict evolutions in the future. In this study, we aimed to investigate the prevalence of seropositivity of antibodies against measles, rubella and mumps in a population of all ages in Youyang, southwest China. A cross-sectional hospital-based study was conducted among 657 cases who attended to Youyang Hospital from Sep 2018 to Aug 2019. Sero IgG antibodies were measured by ELISA. No difference in the seropositivity of antibodies against measles, rubella and mumps was found between neither urban vs. rural, nor male vs. female. The overall seropositivity of anti-measles, rubella, mumps IgG antibodies was 81.1% (95% CI: 78.0-83.9), 65.9% (95% CI: 62.2-69.4) and 63.2% (95% CI: 59.4-66.8), respectively. The IgG seropositivity varied with age significantly. In this study, the seropositivity of antibodies against measles, rubella and mumps among the participants was insufficient in the population, especially among infants, teenagers and productive women, who were suggested to booster the immunity. To better control and eliminate measles, mumps and rubella-related diseases, nation-wide active laboratory-supported surveillance, outbreak investigation and revaccination for vulnerable population are needed.

Decline of serologic immunity to diphtheria, tetanus and pertussis with age suggested a full life vaccination in mainland China.

Background: Diphtheria-tetanus-pertussis (DTP) vaccine has already been involved in national vaccination program for several decades in China. The immunity against these diseases in the people of all ages is not well investigated.Materials and methods: Serum samples were tested for IgG antibodies to diphtheria toxoid (DT), tetanus toxoid (TT) and pertussis toxin (PT) by using commercial ELISA kits.Results: A total of 666 sera of patients from 1 day to 89 years of age was collected from 2018 to 2019. The protective rates of diphtheria, tetanus and pertussis were 45.5%, 54.4% and 4.7%, respectively. Only 4.7% of the study population had seropositivity against three of the diseases. Young infant (<3 m) and adult (>18y) were generally lack of protective antibody against diphtheria (81.7% and 58.3%) and tetanus (91.5% and 86.2%). An obvious increase in immunity level of diphtheria and tetanus was observed at 3 m-3y, but there was no significant increase of immunity to pertussis at any age group. All age groups showed low immunity to pertussis.Conclusions: The present results revealed the susceptibility to diphtheria and tetanus in young infants and adults, and the susceptibility to pertussis over the ages, which highlight the need to improve the current vaccination program.

One single-center cross-sectional investigation on varicella antibody level of all age groups in Chinese people.

Varicella outbreaks were mainly reported in developed regions with high vaccine coverage, but not in undeveloped areas. It is still not clear that whether the published data of varicella epidemiology could reflect the reality in China or not. In 2019, 657 subjects from People's Hospital of Chongqing Youyang County were included. Anti-varicella-zoster virus (VZV) IgG antibodies were determined by ELISA. The anti-VZV IgG levels were categorized as positive when values were ≥100 mIU/mL. Our results showed that the rates of anti-VZV IgG seropositivity (χ2 = 328.957, P < .0001) and geometric mean titers (P < .0001) were significantly influenced by age. The seropositivity declined dramatically from 84.5% in subjects ≤3 m of age, to 7.9% in subjects of >3 m-1 y (P < .0001). Then, the positivity rate increased slowly as age to 26.7% in >1-<3 y (P = .0006), and 34.5% in 3-<7 y (P = .4294). A steady rise (45.6%) in positivity was observed in subjects aged 7-<18 y. After then, the positivity began to increase robustly. A total of 87.8% of adults aged 18-<40 y had acquired VZV-specific immunity (P < .0001). The highest positivity rate was found in 40-<60 y  (98.3%) and ≥60 y (98.2%) group. In conclusion, most subjects of >3 m-<7 y age were susceptible to VZV. The proportion of subjects with natural infection-induced immunity increased with age. Nearly all subjects over 40 ages had positive anti-VZV IgG antibodies, which proved that they were infected by this virus in the past. These results suggested that VarV should be included in the national immunization program in China.

Targeting GRP78 as a Basis for Enhanced Glioma Cells Killing by anti-TfR antibody.

AIM: Studies have shown that chemotherapeutic drugs induced endoplasmic reticulum (ER) stress in glioblastoma cells. In our previous study, we have demonstrated anti-TfR monoclonal antibody 7579 enhanced the anti-tumor effects of chemotherapeutic drugs on human glioma cells in vitro. In our study, we therefore investigated whether the anti-TfR antibody alone or the combination of anti-TfR antibody with chemotherapeutic drug would lead to increased ER stress. MATERIAL AND METHODS: We detected ER stress after cells were treated with anti-TfR mAb or/and Nimustine by western blot analysis. We detected the colony survival and apoptosis of cells after transfection with siRNA and treated with anti-TfR mAb or/and Nimustine by lableing with methylene blue and FCM. RESULTS: The anti-TfR antibody could elevate expression GRP78/BiP and CHOP/GADD153 and lead to further increased ER stress when combined with Nimustine. Small interfering RNA (siRNA) against the ER stress marker GRP78 further sensitized the glioma cells to killing by the anti-TfR antibody or/and Nimustine. CONCLUSION: Our results show that the anti-tumor effects of anti-TfR antibody trigger the ER stress response, and that this effect is achieved via the siRNA against GRP78 for glioma cell growth and survival. These results hold promise as a clinical approach to gene therapy for malignant gliomas.

Combination of Curcumin with an Anti-Transferrin Receptor Antibody Suppressed the Growth of Malignant Gliomas In vitro.

AIM: Transferrin receptor (TfR) has been used as a target for the molecular cancer therapy due to its higher expression in a variety of tumors. Anti-TfR antibodies combined with chemotherapeutic drugs has showed great potential as a possible cancer therapeutic strategy. In our study, we investigated the anti-tumor effects of anti-TfR monoclonal antibody (mAb) alone or in combination with curcumin in vitro. MATERIAL AND METHODS: We detected the apoptosis, proliferation and cell cycle of glioma cells after treated with anti-TfR mAb and curcumin alone or the combinations by flow cytometer. RESULTS: Anti-TfR mAb or curcumin could inhibit proliferation of tumor cells. Anti-TfR mAb marked S phase arrest and curcumin induced G2/M arrest in tumor cells. When anti-TfR mAb and curcumin were used simultaneously, a synergistic effect was detected in relation to tumor growth inhibition and the induction of cells necrosis. CONCLUSION: These results provided a potential role of anti-TfR mAb-containing curcumin in the treatment for gliomas.

In-Situ Welding Carbon Nanotubes into a Porous Solid with Super-High Compressive Strength and Fatigue Resistance.

Carbon nanotube (CNT) and graphene-based sponges and aerogels have an isotropic porous structure and their mechanical strength and stability are relatively lower. Here, we present a junction-welding approach to fabricate porous CNT solids in which all CNTs are coated and welded in situ by an amorphous carbon layer, forming an integral three-dimensional scaffold with fixed joints. The resulting CNT solids are robust, yet still highly porous and compressible, with compressive strengths up to 72 MPa, flexural strengths up to 33 MPa, and fatigue resistance (recovery after 100,000 large-strain compression cycles at high frequency). Significant enhancement of mechanical properties is attributed to the welding-induced interconnection and reinforcement of structural units, and synergistic effects stemming from the core-shell microstructures consisting of a flexible CNT framework and a rigid amorphous carbon shell. Our results provide a simple and effective method to manufacture high-strength porous materials by nanoscale welding.

[Changes of immune function in liver cirrhosis patients after splenectomy combined with resection of hepatocellular carcinoma].

OBJECTIVE: To study the changes of immune function in liver cirrhosis patients after splenectomy combined with resection of hepatocellular carcinoma (HCC). METHODS: Sixteen patients with HCC associated with liver cirrhosis were divided into two groups: splenectomy combined with hepatectomy (n = 7) and hepatectomy (n = 9). T-lymphocyte subsets such as CD4, CD8, CD4/CD8 and Th-lymphocyte cytokines such as IFN-gamma, IL2, IL10 in 7 ml peripheral venous blood before operation and two months after operation were examined and compared between the two groups. RESULTS: There was no significant difference in pre-operative CD4, CD4/CD8, IL2, IFN-gamma, IL10 levels in the two group. Two months after operation, the levels of CD4 (38.2% +/- 3.7%), CD4/CD8 (1.7 +/- 0.3), IFN-gamma [(104.4 +/- 14.9) pg/ml], IL2 [(98.6 +/- 18.6) pg/ml] were increased and those of CD8 (23.7 +/- 13.7) pg/ml and IL10 [(55.5 +/- 11.2) pn/ml] were decreased in the two groups, but the changes in the group of splenectomy combined with hepatectomy were more obvious than those in the hepatectomy group. The levels of CD4 (32.5% +/- 4.0%), CD4/CD8 (1.1 +/- 0.1), IFN-gamma [(70.5 +/- 12.6) pg/ml], IL2 [(80.9 +/- 13.5) pg/ml] in the group of splenectomy combined with hepatectomy, were much higher than those in the hepatectomy group; those of CD8 (29.4% +/- 4.0%), IL10 [(89.4 +/- 10.0) pg/ml] level were significantly lower than those in the hepatectomy (P < 0.05). CONCLUSION: Splenectomy combined with hepatectomy for HCC associated with liver cirrhosis donor decrease but promote the recover T-lymphocyte subsets and Th1/Th2 cytokines from imbalance and improve the patient's antitumor immune function.