Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KRP (KIP-RELATED PROTEIN) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with SHOOT MERISTEMLESS (STM), which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Effect of acupuncture at the acupoints for Yizhi Tiaoshen on the functional connectivity between the hippocampus and the brain in the patients with Alzheimer's disease. / 针刺"益智调神"ç©´æ–¹å¯¹é˜¿å°”èŒ¨æµ·é»˜ç— æ‚£è€ æµ·é©¬ä¸Žå ¨è„‘åŠŸèƒ½è¿žæŽ¥çš„å½±å“.

OBJECTIVES: To analyze the effect of acupuncture at the acupoints for Yizhi Tiaoshen (benefiting the intelligence and regulating the spirit) on the functional connectivity between the hippocampus and the whole brain in the patients with Alzheimer's disease (AD), and reveal the brain function mechanism of acupuncture in treatment of AD using resting state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty patients with mild to moderate AD were randomly divided into an acupuncture + medication group (30 cases, 3 cases dropped out) and a western medication group (30 cases, 2 cases dropped out). In the western medication group, the donepezil hydrochloride tablets were administered orally, 2.5 mg to 5 mg each time, once daily; and adjusted to be 10 mg each time after 4 weeks of medication. Besides the therapy as the western medication group, in the acupuncture + medication group, acupuncture was supplemented at the acupoints for Yizhi Tiaoshen, i.e. Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Xuanzhong (GB 39). The needles were retained for 30 min in one treatment, once daily; and 6 treatments were required weekly. The duration of treatment was 6 weeks in each group. The general cognitive function was assessed by the mini-mental state examination (MMSE) and Alzheimer's disease assessment scale-cognitive part (ADAS-Cog) before and after treatment in the two groups. Using the rs-fMRI, the changes in the functional connectivity (FC) of the left hippocampus and the whole brain before and after treatment were analyzed in the patients of the two groups (11 cases in the acupuncture + medication group and 12 cases in the western medication group). RESULTS: After treatment, compared with those before treatment, MMSE scores increased and ADAS-Cog scores decreased in the two groups (P<0.05); MMSE score was higher, while the ADAS-Cog score was lower in the acupuncture + medication group when compared with those in the western medication group (P≤0.05). After treatment, in the western medication group, FC of the left hippocampus was enhanced with the left fusiform gyrus, the inferior frontal gyrus of the left triangular region, the bilateral superior temporal gyrus and the right superior parietal gyrus (P<0.05), while FC was weakened with the left inferior temporal gyrus, the left middle frontal gyrus and the right dorsolateral superior frontal gyrus when compared with that before treatment (P<0.05). After treatment, in the acupuncture + medication group, FC of the left hippocampus was increased with the right gyrus rectus, the left inferior occipital gyrus, the right superior temporal gyrus and the left middle occipital gyrus (P<0.05), and it was declined with the left thalamus (P<0.05) when compared with those before treatment. After treatment, in the acupuncture + medication group, FC of the left hippocampus was strengthened with the bilateral inferior temporal gyrus, the bilateral middle temporal gyrus, the right gyrus rectus, the bilateral superior occipital gyrus, the left lenticular nucleus putamen, the left calcarine fissure and surrounding cortex, the inferior frontal gyrus of the left insulae operculum, the left medial superior frontal gyrus and the right posterior central gyrus (P<0.05) compared with that of the western medication group. CONCLUSIONS: Acupuncture at the acupoints for Yizhi Tiaoshen improves the cognitive function of AD patients, and its main brain functional mechanism is related to intensifying the functional connectivity of the left hippocampus with the default network (inferior temporal gyrus, middle temporal gyrus and superior frontal gyrus, gyrus rectus), as well as with the sensory (posterior central gyrus) and visual (calcarine fissure and surrounding cortex and superior occipital gyrus) brain regions.

Nano-Brush Structure for Rapid Label-Free Differentiation of Alzheimer's Disease Stages and Direct Capture of Neuron-Derived Exosomes from Human Blood Plasma.

The measurement of the neurofilament light chain (NFL) in human blood plasma/serum is a promising liquid biopsy for Alzheimer's disease (AD) diagnosis, offering advantages over conventional neuroimaging techniques recommended in clinical guidelines. Here, a controllable nano-brush structure comprising upstanding silicon nanowires coated with indium tin oxide was employed as the sensing substrate. This nano-brush structure was modified with an NFL antibody (NFLAb) via silane coupling and then further connected as the extended gate in a field-effect transistor (EGFET). Notable signal differences emerged within a 2 min timeframe, enabling the label-free differentiation in human blood plasmas among four distinct cohorts: healthy controls, subjective cognitive decline, mild cognitive impairment, and dementia due to AD. Our study indicates that achieving a surface roughness exceeding 400 nm on the modified nano-brush structure enables the effective electrical sensing in our EGFETs. These distinct electrical responses measured via the NFLAb-modified nano-brush EGFETs can be attributed to the combined effects of the captured NFLs and NFL-specific neuron-derived exosomes (NDEs) found in dementia patients, as confirmed by electron spectroscopy for chemical analysis, atomic force microscopy, and scanning electron microscopy. Finally, the potential of quantitatively detecting NDEs on the NFLAb-modified nano-brush structure was demonstrated using spiked solutions containing NFL-specific NDEs from IMR-32 neuroblast cells, wherein concentration-dependent changes were observed in the EGFETs output signal. Our findings show that the NFLAb-modified nano-brush EGFET enables rapid, label-free differentiation between healthy individuals and patients at varying stages of AD.

Delta radiomics analysis for prediction of intermediary- and high-risk factors for patients with locally advanced cervical cancer receiving neoadjuvant therapy.

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann-Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models-the clinical model, the radiomics model, and the combined clinic and radiomics model-were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.

Glucose status within dark-grown etiolated cotyledons determines seedling de-etiolation upon light irradiation.

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.

[Effects of Yizhi Tiaoshen acupuncture on learning and memory function and the expression of phosphorylated tau protein in the hippocampus of Alzheimer's disease model rats].

OBJECTIVE: To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD. METHODS: A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3ß (GSK-3ß) in the hippocampus was detected. RESULTS: There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3ßwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3ß was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05). CONCLUSION: Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3ß and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.

Sugar status in preexisting leaves determines systemic stomatal development within newly developing leaves.

Stomata are pores found in the epidermis of stems or leaves that modulate both plant gas exchange and water/nutrient uptake. The development and function of plant stomata are regulated by a diverse range of environmental cues. However, how carbohydrate status in preexisting leaves might determine systemic stomatal formation within newly developing leaves has remained obscure. The glucose (Glc) sensor HEXOKINASE1 (HXK1) has been reported to decrease the stability of an ethylene/Glc signaling transcriptional regulator, EIN3 (ETHYLENE INSENSITIVE3). EIN3 in turn directly represses the expression of SUC2 (sucrose transporter 2), encoding a master transporter of sucrose (Suc). Further, KIN10, a nuclear regulator involved in energy homeostasis, has been reported to repress the transcription factor SPCH (SPEECHLESS), a master regulator of stomatal development. Here, we demonstrate that the Glc status of preexisting leaves determines systemic stomatal development within newly developing leaves by the HXK1-¦EIN3-¦SUC2 module. Further, increasing Glc levels in preexisting leaves results in a HXK1-dependent decrease of EIN3 and increase of SUC2, triggering the perception, amplification and relay of HXK1-dependent Glc signaling and thereby triggering Suc transport from mature to newly developing leaves. The HXK1-¦EIN3-¦SUC2 molecular module thereby drives systemic Suc transport from preexisting leaves to newly developing leaves. Subsequently, increasing Suc levels within newly developing leaves promotes stomatal formation through the established KIN10⟶ SPCH module. Our findings thus show how a carbohydrate signal in preexisting leaves is sensed, amplified and relayed to determine the extent of systemic stomatal development within newly developing leaves.

Effect and Mechanism of Sodium Butyrate on Neuronal Recovery and Prognosis in Diabetic Stroke.

Ischemic stroke is a cerebrovascular lesion caused by local ischemia and hypoxia. Diabetes mellitus (DM) is a chronic inflammatory disease that disturbs immune homeostasis and predisposes patients to ischemic stroke. The mechanism by which DM exacerbates stroke remains unclear, although it may involve disturbances in immune homeostasis. Regulatory T cells (Tregs) play a regulatory role in many diseases, but the mechanism of Tregs in diabetes complicated by stroke remains unclear. Sodium butyrate is a short-chain fatty acid that increases Treg levels. This study examined the role of sodium butyrate in the prognosis of neurological function in diabetic stroke and the mechanism by which Tregs are amplified in the bilateral cerebral hemispheres. We evaluated the brain infarct volume, observed 48-h neuronal injury and 28-day behavioral changes, and calculated the 28-day survival rate in mice. We also measured Treg levels in peripheral blood and brain tissue, recorded changes in the blood‒brain barrier and water channel proteins and neurotrophic changes in mice, measured cytokine levels and peripheral B-cell distribution in bilateral hemispheres and peripheral blood, and examined the polarization of microglia and the distribution of peripheral T-cell subpopulations in bilateral hemispheres. Diabetes significantly exacerbated the poor prognosis and neurological deficits in mice with stroke, and sodium butyrate significantly improved infarct volume, prognosis, and neurological function and showed different mechanisms in brain tissue and peripheral blood. The potential regulatory mechanism in brain tissue involved modulating Tregs/TGF-ß/microglia to suppress neuroinflammation, while that in peripheral blood involved improving the systemic inflammatory response through Tregs/TGF-ß/T cells.

[Different operation sequences between acupuncture and cupping therapy for lumbar muscle strain with cold and dampness: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy on lumbar muscle strain with cold and dampness between the different operation sequences of acupuncture and cupping therapy. METHODS: Seventy-six patients with lumbar muscle strain with cold and dampness were randomly divided into an acupuncture + cupping group (A + C group, 38 cases) and a cupping + acupuncture group (C + A group, 38 cases, 1 case dropped off). In the A + C group, cupping therapy was delivered 10 min after the end of treatment with acupuncture, while in the C + A group, acupuncture therapy was exerted 10 min after the end of treatment with cupping. Acupuncture was applied to Mingmen (GV 4), Yaoyangguan (GV 3), ashi point and bilateral Shenshu (BL 23), Dachangshu (BL 25), Weizhong (BL 40) and Yanglingquan (GB 34), and the needles were retained for 30 min in each intervention. Flash cupping was operated along the bilateral sides of the lumbar spine for 3 min, and the cups were retained for 10 min at bilateral Shenshu (BL 23), Dachangshu (BL 25) and ashi points. The intervention was delivered once every two days, 3 times weekly, for 3 weeks totally in each group. The scores of visual analogue scale (VAS) and Oswestry disability index (ODI), TCM syndrome score and the mean temperature of the lumbar region before and after treatment were compared between the two groups. The safety and the clinical efficacy were assessed for the interventions of the two groups. RESULTS: Compared with the values before treatment, except for the sleep score of ODI, the VAS scores, ODI scores and TCM syndrome scores were decreased after treatment (P<0.01, P<0.05); while the mean temperature of the lumbar region was increased (P<0.01) in both groups. After treatment, the VAS score and the pain score of ODI in the C + A group were lower than those in the A + C group (P<0.05). The incidence rate of adverse reactions of the C + A group was lower than that of the A + C group (P<0.01). The effective rate in the A+C group was 92.1% (35/38), that in the C+A group was 94.6%(35/37), there was no statistical difference between the two groups (P>0.05). CONCLUSION: Different operation sequences between acupuncture and cupping therapy obtain the similar efficacy on lumbar muscle strain with cold and dampness, but cupping therapy delivered prior to acupuncture has certain advantages in relieving pain and improving safety.

The prevalence and characteristics of alexithymia in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Alexithymia is common in patients with type 2 diabetes mellitus (T2DM). Although the estimated prevalence of alexithymia in patients with T2DM is widely reported, these results have not been synthesized. AIM: To systematically assess the prevalence and characteristics of alexithymia in patients with T2DM. METHODS: We searched for relevant publications in PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database, and Weipu Database. The prevalence of alexithymia, the mean scores, and standard deviations of the total scale of the 20-item Toronto Alexithymia Scale (TAS-20) were pooled using random effects meta-analysis in Stata 13.0, with studies stratified by study location in this meta-analysis. RESULTS: This meta-analysis included thirteen articles. Pooled prevalence of alexithymia (TAS-20 total scores ≥61) were 43.0% (95%CI 35.0-51.0%), and the prevalence of alexithymia was higher in China (45.0%, 95%CI 36.0-54.0%) compared with non-China (41.0%, 95%CI 29.0-54.0%). The pooled mean score for the TAS-20 total scale was 57.70 (95% CI 55.25-60.15). Leave-one-out analysis showed that none of the studies significantly impacted the overall pooled results. CONCLUSIONS: This meta-analysis indicated a high prevalence of alexithymia in patients with T2DM. Thus, clinicians need to be aware of and assess appropriately for alexithymia in patients with T2DM.

[Research progress on the mechanism of acupuncture intervention on Alzheimer's disease].

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly. Studies have shown that acupuncture can effectively alleviate the symptoms of AD and slow down the disease progression, and its mechanism has been intensively explored. This paper summarized the researches on the mechanism of acupuncture intervention on AD in the past 5 years. It has been found that acupuncture intervention on AD is correlated with the regulation of the expression levels of relevant proteins, the inhibition of central inflammatory response, the resistance to oxidative stress injury, the modulation of brain energy metabolism, the improvement of neuronal synaptic plasticity, the adjustment of autophagy activity and the suppression of neuronal apoptosis.

Increasing burden of major trauma in elderly adults during 2003-2015: Analysis of real-world data from Taiwan.

BACKGROUND: Major trauma has been one of the leading causes of morbidity, mortality, and functional disability, resulting in substantial societal burden. The aim of this study was to estimate the trends in burden of adult major trauma in Taiwan during 2003-2015. METHODS: Adult patients with initial encounter of major trauma (injury severity score ≥ 16) were abstracted from the claim data of National Health Insurance (NHI) in Taiwan from January 2003 to December 2015. We explored the trends of incidence and mortality rates over time stratified by age and sex, as well as life expectancy (LE), loss-of-LE, lifetime healthcare expenditure and total loss-of-LE compared with age, sex and calendar-year matched referents simulated from the vital statistics of Taiwan. RESULTS: A total of 71,731 cases of adult major trauma, and an estimated loss of 979,676 life-years were found with an increasing trend in cumulative incidence rate (CIR18-84) during 2003-2015. The incidence rates were significantly higher in men than women. For both sexes, the incidence rates for those aged 65 and above were about 2-3 times higher than those of all other age groups. The one-year case fatality rates among the elderly were about 31-61%, higher than all other ages. The lifetime healthcare expenditures per person were 47,616 USD in men and 43,416 USD in women. CONCLUSION: There is a consistently increasing trend in incidence and mortality of major trauma in Taiwan, especially among elderly people. For Taiwan, an aged society beginning since 2018, the challenge should be tackled more effectively in the coming decades.

Incidence and time trends of herpes zoster among patients with head and neck cancer who did and did not undergo radiotherapy: A population-based cohort study.

PURPOSE: This study aimed to determine the risk and time trends of herpes zoster among patients with head and neck cancer, with or without radiotherapy. METHODS: A total of 2160 patients with head and neck cancer were enrolled. The radiotherapy and non- radiotherapy cohorts were frequency-matched at a 1:1 ratio according to sex, age, and index date. Moreover, 1080 matched non-cancer individuals were considered normal controls. Data were obtained from the National Health Insurance Research Database and Cancer Registry. The primary end point was the incidence of herpes zoster, and the adjusted confounding factors were age, sex, comorbidities, oncological surgery, and chemotherapy. RESULTS: The incidence of herpes zoster was higher in cancer patients than in non-cancer individuals but did not significantly differ (13.67 vs. 8.06 per 1,000 person-years, p = 0.18). The risk of herpes zoster was significantly higher in the radiotherapy cohort than in the non-radiotherapy cohort (18.55 vs. 9.06 per 1,000 person-years, p = 0.03). The 5-year incidence rates in the radiotherapy and non-radiotherapy cohorts were 8.9% and 5%, respectively (p < 0.0001). Survival analysis indicated there was no immortal time bias. The time trends in the radiotherapy cohort persistently showed a high risk within the first 2 years, which decreased thereafter. Only patients with comorbid rheumatoid arthritis showed a significantly high risk of herpes zoster (p = 0.02). Oncological surgery and chemotherapy had no impact on the development of herpes zoster. CONCLUSIONS: This nationwide population-based study showed that patients with head and neck cancer receiving radiotherapy are at an increased risk of herpes zoster. Health care professionals should pay more attention to this vulnerable group to improve their quality of life.

[Formation and Prevention of Secondary Nitrate in PM2.5 in Tianjin].

To study the formation and approaches to controlling secondary nitrate in PM2.5, the ionic compositions of PM2.5, pH of aerosols, variations in NH3-NH4+ and HNO3-NO3- concentrations, and the joint NH3/HNO3 sensitivity regime map of ammonium nitrate were investigated based on high-resolution online monitoring data for an urban site in central Tianjin from 2018 to 2019. The results showed that the average concentration of PM2.5 was 58µg·m-3, and the main ionic compositions of PM2.5 were nitrate (NO3-), ammonium (NH4+), sulfate (SO42-), Cl-, and K+ with corresponding mass percentages of 18.4%, 11.6%, 10.3%, 3.3%, and 2.6%, respectively. Concentrations of PM2.5 and the main components were relatively high during the heating season and relatively low during the non-heating season. The aerosols were weakly acidity with an average pH of 5.21; pH was higher in spring and winter and lower in summer and autumn, and diurnal variations pH were lower in the morning (00:00-08:00) and slightly higher at other times. The concentrations of NH3(g) (gas NH3) and HNO3(g) (gas HNO3) were 16.7µg·m-3and 1.2µg·m-3, respectively. The concentrations of NH3(g) were relatively higher from April to September and lower from October to February of the following year. HNO3(g) concentrations did not show any clear monthly pattern. Except during the summer, NH3(g) concentrations were higher in the morning and evening, and HNO3(g) concentrations were higher during the day. No clear linear relationships were observed between the concentrations of NH3(g) and NH4+ nor the concentrations of HNO3(g) and NO3- at different pH levels. Higher concentrations of NO3- and NH4+ were observed in the morning and evening, while no linear relationships were observed between the pH and concentrations of NH3(g)-NH4+ and HNO3(g)-NO3-. The joint NH3/HNO3 sensitivity regime map showed that most of the points were located in the HNO3 sensitive region with some in the NH3 & HNO3 sensitive region. In spring, autumn, and winter, most of the points were located in the HNO3 sensitive region while in summer, a significant quantity of the points were located in the NH3 & HNO3 sensitive region. Therefore, the precursors of HNO3 (such as NOx) should be controlled in the spring, autumn, and winter, and attention should be given to the control of the precursors of HNO3 (NOx) and NH3 in the summer to effectively control nitrate and ammonium aerosols in PM2.5 in Tianjin.

Integrative analysis of epigenomics, transcriptomics, and proteomics to identify key targets and pathways of Weining granule for gastric cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Weining granule (WNG) is a "Qi-Enriching and Kidney-Tonifying, Spleen-Reinforcing and Stasis-Removing" formula for gastric cancer (GC). Past research we noted WNG inhibited cell growth and raised apoptosis in GC. However, the underlying mechanism of WNG for GC have yet to be systematically clarified. AIM OF THE STUDY: We sought to characterize the molecular landscape of GC cells in vitro after WNG treated, to identify the molecular targets and pathways that were associated with WNG for inducing the apoptosis of GC cells, and further to clarify underlying molecular mechanism of WNG for GC. MATERIALS AND METHODS: We performed the techniques of RNA sequencing, tandem mass tags (TMT) based quantitative proteomics, and reduced representation bisulfite sequencing (RRBS) in WNG-treated/or untreated SGC-7901 GC cells to gain a comprehensive molecular portrait of WNG treatment. Then we integrated methylomics, transcriptomics, and proteomics data to carry out the bioinformatics analysis, and constructed the protein-protein interaction (PPI) network to identify molecular targets, and to discover the underlying signaling pathways associated with WNG for GC by network analysis. Besides, we verified the candidate target genes by Kaplan-Meier plotter database. RESULTS: We identified 1249 significant differentially expressed genes (DEGs) from RNA expression datasets, 191 significant differentially abunabundant proteins (DAPs) from proteomics datasets, and 8293 significant differentially methylated regions (DMRs) from DNA methylation datasets. GO and KEGG analysis showed DEGs, DAPs, and DMRs enriched in the cancer-related biological processes of calcium signaling pathway, pathways in cancer, metabolic pathways, MAPK signaling pathway, PI3K-Akt signaling pathway, and transcriptional misregulation in cancer. We integrated three profile datasets and performed network analysis to distinguish the hub genes, and finally the genes of SOD2, HMOX1, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, POLR2F, and HSPA9 were identified. The Kaplan-Meier plotter confirmed that SOD2, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, and HSPA9 were significantly correlated with OS in GC patients (P < 0.01), while HMOX1 and POLR2F expression were not significantly relevant to survival of GC patients (P > 0.01). CONCLUSIONS: SOD2, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, and HSPA9 were the predictive pharmaceutical targets of WNG for GC. The anticancer function of WNG was significantly associated with the pathways of focal adhesion pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and Wnt signaling pathway.

Morpho-physiological properties and connectivity of vasoactive intestinal polypeptide-expressing interneurons in the mouse hippocampal dentate gyrus.

The hippocampus is a key brain structure for cognitive and emotional functions. Among the hippocampal subregions, the dentate gyrus (DG) is the first station that receives multimodal sensory information from the cortex. Local-circuit inhibitory GABAergic interneurons (INs) regulate the excitation-inhibition balance in the DG principal neurons (PNs) and therefore are critical for information processing. Similar to PNs, GABAergic INs also receive distinct inhibitory inputs. Among various classes of INs, vasoactive intestinal polypeptide-expressing (VIP+ ) INs preferentially target other INs in several brain regions and thereby directly modulate the GABAergic system. However, the morpho-physiological characteristics and postsynaptic targets of VIP+ INs in the DG are poorly understood. Here, we report that VIP+ INs in the mouse DG are highly heterogeneous based on their morpho-physiological characteristics. In approximately two-thirds of morphologically reconstructed cells, their axons ramify in the hilus. The remaining cells project their axons exclusively to the molecular layer (15%), to both the molecular layer and hilus (10%), or throughout the entire DG layers (8%). Generally, VIP+ INs display variable intrinsic properties and discharge patterns without clear correlation with their morphologies. Finally, VIP+ INs are recruited with a long latency in response to theta-band cortical inputs and preferentially innervate GABAergic INs over glutamatergic PNs. In summary, VIP+ INs in the DG are composed of highly diverse subpopulations and control the DG output via disinhibition.

Radiotherapy combined with chemotherapy increases the risk of herpes zoster in patients with gynecological cancers: a nationwide cohort study.

OBJECTIVE: This study aimed to determine the effect of radiotherapy (RT) on the risk of herpes zoster (HZ) in patients with gynecological cancers via a nationwide population-based study. METHODS: Based on patient data obtained from the National Health Insurance Research Database, 1928 gynecological cancer patients were identified with 1:1 matching for RT and non-RT cohorts by age, index date, and cancer type. Another cohort consisting of 964 non-cancer individuals matched was used as normal control. The incidence of HZ was compared between cancer patients with and without RT. Age, comorbidities, cancer-related surgery and chemotherapy (CT), and cancer type were adjusted as confounders. RESULTS: The risk of HZ in cancer patients was higher than that of non-cancer individuals (14.23 versus 8.34 per 1,000 person-years [PY], the adjusted hazard ratio [aHR]=1.38, p=0.044). In the cancer population, the incidence of HZ for the RT and non-RT cohorts was 20.55 versus 10.23 per 1,000 PY, respectively (aHR=1.68, p=0.009). Age >50 years was an independent factor for developing HZ. The 5-year actuarial incidence for patients receiving neither RT nor CT, RT alone, CT alone, and combined modalities was 5.4%, 6.9%, 3.7%, and 9.9%, respectively (p<0.001). In the RT cohort, the risk rose rapidly in the first year, becoming steady thereafter. CONCLUSION: This population-based study showed that gynecological cancer patients receiving RT combined with CT had the highest cumulative risk of HZ. Health care professionals should be aware of the potential toxicities.

[Evaluation of Different ISORROPIA-â ¡ Modes and the Influencing Factors of Aerosol pH Based on Tianjin Online Data].

Aerosol acidity is closely related to particle properties and the explosive growth of secondary particles. Aerosol pH is difficult to measure directly but can be estimated indirectly by thermodynamic equilibrium modeling. ISORROPIA-Ⅱ is one of the most commonly used thermodynamic models and includes different modes (forward and reverse) and aerosol states (stable and metastable). Studies have shown that the calculated pH results vary with the selected mode and phase state. In addition to the selection of modes and phases, there are also other factors that influence the modeling results. In order to explore the appropriate mode and phase selection of ISORROPIA-Ⅱ as well as the factors influencing the model results under the air pollution characteristics of typical Chinese cities, the simulation results of different modes and aerosol states were analyzed by using online hourly data for Tianjin. The results showed that the pH calculations using the forward mode and metastable state were satisfactory at a higher RH. With increased temperature, the pH, aerosol water content, and concentration proportion in the aerosol phase of semi-volatile components all decreased. RH affected aerosol pH by influencing the aerosol water content and concentration of semi-volatile components. An increased cation concentration led to an increased pH and NH3 concentration but a decreased HNO3 concentration, whereas an increased anion concentration had the opposite effect. Ca2+, SO42-, NO3-, and NH4+ had a great influence on pH. Compared with SO42-, NO3- had less effect on pH. Sensitive areas exist in the influence of NH4+ on pH, and a high NH4+ concentration did not cause a continuous pH increase. This study can improve the understanding of aerosol pH simulation using ISORROPIA-Ⅱ, and provides reference for research on the pH-related secondary generation mechanism, semi-volatile component gas-particle distribution, and pollution control measures.