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Spinal intradural (subdural and subarachnoid) hematoma following percutaneous kyphoplasty is an extremely rare complication. In this report, we described a case of 2 episodes of subarachnoid hemorrhage with delayed paralysis after kyphoplasty. A 73-year-old man underwent percutaneous kyphoplasty in our hospital an osteoporotic vertebral fracture at the T12 level. On the 55 h after kyphoplasty for T12 osteoporotic vertebral fracture, he developed paralysis of the lower limbs. An emergency posterior decompression from T8 to L2 was performed. And the subarachnoid hematomas were removed. Postoperatively, the neurological symptoms improved rapidly. However, 2 weeks after the operation, the patient experienced a setback with severe neurological decline (paraplegia with sensory and autonomic dysfunction). An emergency posterior decompression from T5 to L2 was performed. The subarachnoid hematomas were removed. This case reflects the cause and progression of spinal subdural hematoma. Previous literature has debated the best treatment approach for spinal subarachnoid hemorrhage, but the prognosis of patients is heavily dependent on precise symptom evaluation and localization.

Abstract Background Triptans selectively agoniste 5-Hydroxytryptamine(5-HT) receptors and are widely used in the treatment of migraine. Nevertheless, there is a dearth of comprehensive real-world clinical research on the safety of triptans. In light of the growing prevalence of migraine, it is imperative to gain a deeper understanding of the true extent of adverse events (AEs) associated with triptans in the clinical management of migraine. Methods A database query of AEs reported to the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for triptans was performed using the online platform Open Vigil 2.1. The query spanned the period from 1 January 2018 to 31 December 2023 and extracted all AEs for ‘sumatriptan’, ‘zolmitriptan’, ‘rizatriptan’, and ‘naratriptan’ from the 15–49 years old population and retrospective quantitative analyses. A proportional reporting ratio (PRR), reporting odds ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN) methodology were utilized to contrast AEs across the four triptans. Results A total of 1.272 AEs reports for sumatriptan, 114 for zolmitriptan, 162 for rizatriptan, and 15 for naratriptan were identified. The ratio of females to males was approximately three times higher in all cases, with the highest number of reports originating from the Americas. A review of the FAERS database revealed that nervous system disorders were the primary SOC category for four drugs, with all four drugs exhibiting the AE indicative of reversible cerebral vasoconstriction syndrome, also classified as Nervous system disorders. The most frequently reported AE signal for sumatriptan was dyspnea, which is classified as respiratory, thoracic and mediastinal disorders. The most frequently reported AEs signals for the remaining three drugs were nausea, vomiting and terminal ileitis, all of which are classified as gastrointestinal disorders. Conclusion Analyses have demonstrated that AEs are present in a range of systems, including cardiac, nervous, gastrointestinal, and musculoskeletal disorders. It should be noted, however, that the incidence and signal intensity of these AEs vary depending on the specific drug in question. In clinical practice, the selection of an appropriate drug and the monitoring of AEs should be tailored to the individual patient’s and specific characteristics.

A new species from China, Elymus multiramosus Y.C. Zhang, sp. nov. is described and illustrated herein, based on morphological characters and molecular phylogenetic analysis. The taxonomic descriptions of E. multiramosus and the comparison with related species are presented. The taxonomic distinctiveness of this new species was inferred by Maximum Likelihood (ML) analysis and Bayesian phylogenetic analysis, based on the complete chloroplast genome sequence. It is assigned to the Elymus section and bears similarity to Elymus nutans Griseb. However, it can be easily distinguished from other species by its compound spike, in contrast to the simple spike inflorescence typical of those species. The compound spike is characterised by rhachillas that are extended at the base of the main axis, giving rise to 3–6 mini-spike-like branches. Notably, these branches significantly increase in length from the top towards the bottom of the compound spike. In the molecular phylogeny, Elymus multiramosus from Qinghai, north-western China, is phylogenetically positioned as a distinct lineage. The lineage comprising Elymus sinosubmuticus from Sichuan, east of the Tibetan Plateau and Elymus nutans from the Himalayas forms a sister group to Elymus multiramosus, suggesting that these three species share a common ancestor that is distinct from the lineage leading to Elymus atratus from Gansu, north of the Tibetan Plateau.

PurposePostherpetic neuralgia (PHN) is a type of refractory neuropathic pain that causes significant suffering, disability, economic loss, and medical burden. In this study, we aim to evaluate the efficacy and safety of interferon (IFN)-α1b injection into the intervertebral foramen of patients with PHN.Patients and methodsThis is a study protocol for a randomized, double-blind placebo-controlled multicenter clinical trial. A total of 200 participants with PHN from 11 hospitals will be recruited and randomly assigned to the treatment group administered with IFN-α1b and control group treated with placebo in a 1:1 ratio. Both groups will also receive oral pregabalin 150 mg twice daily and lidocaine injection into the intervertebral foramen as conventional therapy. This trial will involve a screening period, a 2-week intervention, and a 3-month follow-up. The primary outcomes will include the visual analog scale score and duration of pain relief. The secondary outcomes will include the 36-item short-form, dosage and duration of painkillers taken, viral load of varicella-zoster virus DNA, humoral cytokine level, and dosage and frequency of rescue medication. All adverse events and severe adverse events will be assessed during the study.ConclusionThis study is expected to provide evidence for the efficacy and safety of IFN-α1b injection into the intervertebral foramen in patients with PHN.Clinical trial registrationhttps://www.chictr.org.cn/indexEN.html, identifier ChiCTR240008996.

Abstract Background Quantitative evidence on the impact of meteorological factors on influenza transmissibility across different virus types/subtypes is scarce, and no previous studies have reported the effect of hourly temperature variability (HTV) on influenza transmissibility. Herein, we explored the associations between meteorological factors and influenza transmissibility according to the influenza type and subtype in Guangzhou, a subtropical city in China. Methods We collected influenza surveillance and meteorological data of Guangzhou between October 2010 and December 2019. Influenza transmissibility was measured using the instantaneous effective reproductive number (R t ). A gamma regression with a log link combined with a distributed lag non-linear model was used to assess the associations of daily meteorological factors with R t by influenza types/subtypes. Results The exposure-response relationship between ambient temperature and R t was non-linear, with elevated transmissibility at low and high temperatures. Influenza transmissibility increased as HTV increased when HTV

Establishing cultivated grassland in the Qinghai-Tibet Plateau region is an effective method to address the conflict between vegetation and livestock. However, the high altitude, low temperature, and arid climate in the region result in slow regeneration and susceptibility to degradation of mixed cultivation grassland containing perennial legumes and gramineous plants. Therefore, we aim to through field experiments, explore the feasibility of establishing mixed cultivation grassland of Poaceae species in the region by utilizing two grass species, Poa pratensis L. and Puccinellia tenuiflora. By employing a mixture of P. pratensis and P. tenuiflora to establish cultivated grassland, we observed significant changes in forage yield over time. Specifically, during the 3rd to 6th years of cultivation, the yield in the mixed grassland was higher than in monocultures. It exceeded the yield of monoculture P. tenuiflora by 19.38% to 29.14% and surpassed the monoculture of P. pratensis by 17.18% to 62.98%. Through the analysis of soil physicochemical properties and soil microbial communities in the cultivated grassland, the study suggests that the mixed grassland with Poaceae species can enhance soil enzyme activity and improve soil microbial communities. Consequently, this leads to increased soil nutrient levels, enhanced nitrogen fixation efficiency, and improved organic phosphorus conversion efficiency. Therefore, establishing mixed grasslands with Poaceae species in the Qinghai-Tibet Plateau region is deemed feasible.

BackgroundThe GABRA1 gene, encoding the GABRAR subunit α1, plays vital roles in inhibitory neurons. Previously, the GABRA1 gene has been identified to be associated with developmental and epileptic encephalopathy (DEE) and idiopathic generalized epilepsy (IGE). This study aims to explore the phenotypic spectrum of GABRA1 and molecular subregional effect analysis.MethodsTrios-based whole-exome sequencing was performed in patients with epilepsy. Previously reported GABRA1 mutations were systematically reviewed to analyze the molecular subregional effects.ResultsDe novo GABRA1 mutations were identified in six unrelated patients with heterogeneous epilepsy, including three missense mutations (p.His83Asn, p.Val207Phe, and p.Arg214Cys) and one frameshift mutation (p.Thr453Hisfs*47). The two missense mutations, p.His83Asn and p.Val207Phe, were predicted to decrease the protein stability but no hydrogen bond alteration, with which the two patients also presented with mild genetic epilepsy with febrile seizures plus and achieved seizure-free status by monotherapy. The missense variant p.Arg214Cys was predicted to decrease protein stability and destroy hydrogen bonds with surrounding residues, which was recurrently identified in three cases with severe DEE. The frameshift variant p.Thr453Hisfs*47 was located in the last fifth residue of the C-terminus and caused an extension of 47 amino acids, with which the patients presented with moderated epilepsy with generalized tonic-clonic seizures alone (GTCA) but achieved seizure-free status by four drugs. The four variants were not presented in gnomAD and were evaluated as “pathogenic/likely pathogenic” according to ACMG criteria. Analysis of all reported cases indicated that patients with mutations in the N-terminal extracellular region presented a significantly higher percentage of FS and DEE, and the patients with variants in the transmembrane region presented earlier seizure onset ages.SignificanceThis study suggested that GABRA1 variants were potentially associated with a spectrum of epilepsies, including EFS+, DEE, and GTCA. Phenotypic severity may be associated with the damaging effect of variants. The molecular subregional effects help in understanding the underlying mechanism of phenotypic variation.

AIM: To analyze the diagnostic value of macular ganglion cell complex(mGCC)and thickness and visual field of peripapillary retinal nerve fiber layer(pRNFL)on neovascular glaucoma(NVG).METHODS: Retrospective study. A total of 92 patients(100 eyes)with NVG who were admitted to our hospital from January 2018 to October 2021 were selected. They were divided into 31 cases(32 eyes)with early NVG, 31 cases(36 eyes)with open angle glaucoma and 30 cases(32 eyes)with angle-closure glaucoma according to their pathology and term. Additionally, 50 cases(100 eyes)receiving health examination in our hospital at the same period were selected as the control group. Pearson correlation was used to analyze the correlation among mGCC, pRNFL thickness and mean deviation(MD), and the diagnostic efficiency of each index was studied by the receiver operating characteristic(ROC)curve.RESULTS: The levels of mGCC-average(a), mGCC-superior(s)and mGCC-inferior(i)in the patients with early NVG, open-angle glaucoma and angle-closure glaucoma were lower than those in the control group(all P

AIM:To observe the efficacy and safety of RS-type lacrimal drainage tube and annular silicone tube placement in the treatment of lacrimal canaliculus laceration.METHODS: Retrospective study. A total of 64 patients(64 eyes)with lacrimal canaliculus laceration were selected, and divided into group A(34 eyes treated with RS-type lacrimal drainage tube placement)and group B(30 eyes treated with annular silicone tube placement)according to different treatment. Clinical effect, operation time, regression time of postoperative eyelid swelling and complications at 3 and 6mo after surgery were compared between the two groups.RESULTS:There was no statistically significant difference in the total response rate between the two groups at 3mo(94% vs. 87%)and 6mo(91% vs. 83%)after operation(all P

Targeting single tumor antigens makes it difficult to provide sufficient tumor selectivity for T cell engagers (TCEs), leading to undesirable toxicity and even treatment failure, which is particularly serious in solid tumors. Here, we designed novel trispecific TCEs (TriTCEs) to improve the tumor selectivity of TCEs by logic-gated dual tumor-targeting. TriTCE can effectively redirect and activate T cells to kill tumor cells (∼18 pM EC50) by inducing the aggregation of dual tumor antigens, which was ∼70- or 750- fold more effective than the single tumor-targeted isotype controls, respectively. Further in vivo experiments indicated that TriTCE has the ability to accumulate in tumor tissue and can induce circulating T cells to infiltrate into tumor sites. Hence, TriTCE showed a stronger tumor growth inhibition ability and significantly prolonged the survival time of the mice. Finally, we revealed that this concept of logic-gated dual tumor-targeted TriTCE can be applied to target different tumor antigens. Cumulatively, we reported novel dual tumor-targeted TriTCEs that can mediate a robust T cell response by simultaneous recognition of dual tumor antigens at the same cell surface. TriTCEs allow better selective T cell activity on tumor cells, resulting in safer TCE treatment.

Background: Given the limitations of traditional pharmacology pedagogical method, diverse novel teaching methods have been widely explored. In this study, we performed a network meta-analysis (NMA) to evaluate the effects of different strategies in pharmacology education.Methods: Literature databases were searched from their inception to November 2022, and the studies were screened according to predefined inclusion and exclusion criteria to extract important information. Outcomes, including theoretical test scores, experimental test scores, subjective test scores, satisfaction scores, and the proportion of satisfaction, were analyzed using R software (version 3.6.1) and STATA (version 15). The NMA was conducted with a random-effects model under the Bayesian framework to calculate odds ratios (ORs) or mean differences (MDs) with associated 95% credible intervals (95% CIs). Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the teaching methods examined.Results: A total of 150 studies involving 21,269 students were included. This NMA systematically evaluated 24 teaching strategies, such as problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL) and flipped classrooms (FC), etc., The results of the NMA showed that, PBL combined with CBL was most likely to improve students’ theoretical and subjective test scores (SUCRA = 75.49 and 98.19%, respectively), TBL was most likely to improve the experimental test score (SUCRA = 92.38%) and the satisfaction score (SUCRA = 88.37%), while FC had the highest probability of being the best option for improving the proportion of satisfaction (SUCRA = 84.45%).Conclusion: The current evidence indicates that TBL, PBL combined with CBL, and FC might be optimal strategies for pharmacology education since they have a more beneficial effect on students.

Background The global spread of infectious diseases is currently a prominent threat to public health, with the accelerating pace of globalization and frequent international personnel intercourse. The present study examined the epidemiological characteristics of overseas imported cases of acute infectious diseases in Guangzhou, China. Methods We retrospectively investigated the distribution of diseases, demographic characteristics, and temporal and spatial variations of imported cases of acute infectious diseases in Guangzhou based on the surveillance data of notifiable infectious diseases from 2005 to 2019, provided by Guangzhou center for Disease Control and Prevention. The Cochran-Armitage trend test was applied to examine the trend in the number of imported cases over time. Results A total of 1,025 overseas imported cases of acute infectious diseases were identified during the study period. The top three diseases were dengue (67.12%), malaria (12.39%), and influenza A (H1N1) pdm09 (4.10%). Imported cases were predominantly males, with a sex ratio of 2.6: 1 and 75.22% of the cases were those aged 20–49 years. Businessmen, workers, students and unemployed persons accounted for a large proportion of the cases (68.49%) and many of the cases came from Southeast Asia (59.02%). The number of imported cases of acute infectious diseases increased during the study period and hit 318 in 2019. A clear seasonal pattern was observed in the number of imported cases with a peak period between June and November. Imported cases were reported in all of the 11 districts in Guangzhou and the central districts were more seriously affected compared with other districts. Conclusions The burden of dengue imported from overseas was substantial and increasing in Guangzhou, China, with the peak period from June to November. Dengue was the most common imported disease. Most imported cases were males aged 20–49 years and businessmen. Further efforts, such as strengthening surveillance of imported cases, paying close attention to the epidemics in hotspots, and improving the ability to detect the imported cases from overseas, are warranted to control infectious diseases especially in the center of the city with a higher population density highly affected by imported cases. Author summary Guangzhou, a city located in the south of China, is heavily affected by imported infectious disease, with frequent trade, personnel movements and unique subtropical monsoon climate which favors transmissions of various infectious diseases. In this study, we examined the epidemiological characteristics of imported cases of acute infectious diseases in Guangzhou, 2005–2019. Our findings highlighted the potential risk of spread of infectious diseases triggered by imported cases. The top three imported acute infectious diseases were dengue, malaria and influenza A (H1N1)pdm09 and most of the imported cases came from Southeast Asian. The burden of dengue imported from overseas was substantial and increasing in Guangzhou, China, with the peak period from June to November. Most imported cases were males aged 20–49 years and businessmen. Further efforts, such as strengthening surveillance of imported cases, paying close attention to the epidemics in hotspots, and improving the ability to detect the imported cases from overseas, are warranted to control infectious diseases especially in the center of the city with a higher population density highly affected by imported cases.

The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case–control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18–59 years who consisted of SARS-CoV-2 test-positive cases (n = 74) and test-negative controls (n = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6–89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40–59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%.

Abstract Background This study analyzed the trends and seasonality in mortality among children aged 0–14 years in Guangzhou, China during 2008–2018. Understanding the epidemiology of this public health problem can guide policy development for children mortality prevention. Methods A population-based epidemiological retrospective study was conducted. Seven thousand two hundred sixty-five individual data of children mortality were obtained from the Guangzhou Center for Disease Control and Prevention (CDC). The Poisson regression was used to quantify the annual average reduction rate and the difference in mortality rate between sex and age groups. Incidence ratio with 95% confidence interval (CI) was estimated to determine the temperaol variations in mortality by month, season, school term, day of the week and between holidays and other days. Results Between 2008 and 2018, the children mortality rate in Guangzhou decreased from 54.0 to 34.3 per 100,000 children, with an annual reduction rate of 4.6% (95% CI: 1.1%–8.1%), especially the under-5 mortality rate decreased by 8.3% (95% CI: 4.8%–11.6%) per year. Decline trends varied by causes of death, even with an upward trend for the mortality of asphyxia and neurological diseases. The risk of death among males children was 1.33 times (95% CI: 1.20–1.47) of that of females. The distribution of causes of death differed by age group. Maternal and perinatal, congenital and pneumonia were the top three causes of death in infants and cancer accounted for 17% of deaths in children aged 1–14 years. Moreover, the injury-related mortality showed significant temporal variations with higher risk during the weekend. And there was a summer peak for drowning and a winter peak for asphyxia. Conclusions Guangzhou has made considerable progress in reducing mortality over the last decade. The findings of characteristics of children mortality would provide important information for the development and implementation of integrated interventions targeted specific age groups and causes of death.

Abstract Background Anaemia is highly prevalent in gastric cancer (GC) patients. The role of initial haemoglobin levels in predicting the prognosis of GC patients treated by chemotherapy has not been well determined. Our present study aims to evaluate the relationship between the degree of anaemia and the overall survival (OS) and progression-free survival (PFS) of patients with GC. Methods Our retrospective study enrolled 598 patients who were treated with chemotherapy when the recurrent or metastatic GCs were unsuitable for surgical resection. Univariate and multivariate analyses were performed to identify risk factors that had the potential to affect patient prognosis. Additionally, the relationship between clinicopathological characteristics, including treatment method, and degree of cancer-related reduction in haemoglobin was further analysed. Results Our results revealed that patients with HBini level ≤ 80 g/L had a trend toward a shortened median OS and PFS (p = 0.009 and p = 0.049, respectively). Interestingly, we also found that HBdec ≥ 30 g/L was associated with a significantly shortened median OS and PFS (p = 0.039 and p = 0.001, respectively). Multivariate analysis showed that HBini levels ≤80 g/L could be used as an independent prognostic factor for recurrent and metastatic GC. More importantly, HBdec ≥ 30 g/L and treatment response were also significantly associated with OS and PFS. Furthermore, the degree of haemoglobin decrease was associated with chemotherapy including platinum and the number of chemotherapy cycles. Conclusion Our study concludes that the initial degree of anaemia and a decrease in haemoglobin of ≥30 g/L can serve as biomarkers to predict prognosis in recurrent or metastatic GC patients, while chemotherapy treatment rather than red blood cell (RBC) transfusion can improve their prognosis. Additionally, platinum should not be recommended for treating severely anaemic GC patients.

BackgroundThe first community transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant of concern (VOC) in Guangzhou, China occurred between May and June 2021. Herein, we describe the epidemiological characteristics of this outbreak and evaluate the implemented containment measures against this outbreak.Methodology/principal findingsGuangzhou Center for Disease Control and Prevention provided the data on SARS-CoV-2 infections reported between 21 May and 24 June 2021. We estimated the incubation period distribution by fitting a gamma distribution to the data, while the serial interval distribution was estimated by fitting a normal distribution. The instantaneous effective reproductive number (Rt) was estimated to reflect the transmissibility of SARS-CoV-2. Clinical severity was compared for cases with different vaccination statuses using an ordinal regression model after controlling for age. Of the reported local cases, 7/153 (4.6%) were asymptomatic. The median incubation period was 6.02 (95% confidence interval [CI]: 5.42-6.71) days and the means of serial intervals decreased from 5.19 (95% CI: 4.29-6.11) to 3.78 (95% CI: 2.74-4.81) days. The incubation period increased with age (PConclusions/significanceThe hierarchical prevention and control strategy against COVID-19 in Guangzhou was timely and effective. Authorised inactivated vaccines are likely to contribute to reducing the probability of developing severe disease. Our findings have important implications for the containment of COVID-19.

Liuweiwuling Tablet (LWWL) is a licensed Chinese patent medicine (approval number: Z20060238) included in the national health insurance for anti-inflammation of chronic HBV infection, whereas its anti-HBV effect remains clarification. The study aimed to clarify its antiviral effect and related mechanisms. HepG2.2.15 cells (wild-type HBV-replicating cells) and HepG2. A64 cells (entecavir-resistant HBV-replicating cells) were used for in vitro test. Hydrodynamic injection-mediated HBV-replicating mouse model was used for in vivo test. Active compounds and related mechanisms for antiviral effect of LWWL were analyzed using network pharmacology and transcriptomics. The inhibition rates of LWWL (0.8 mg/ml) on HBV DNA, HBsAg, and pgRNA were 57.06, 38.55, and 62.49% in HepG2.2.15 cells, and 51.57, 17.57, and 53.88% in HepG2. A64 cells, respectively. LWWL (2 g kg−1 d−1 for 4 weeks)-treated mice had 1.16 log10 IU/mL decrease of serum HBV DNA, and more than 50% decrease of serum HBsAg/HBeAg and hepatic HBsAg/HBcAg. Compared to tenofovir control, LWWL was less effective in suppressing HBV DNA but more effective in suppressing HBV antigens. Thirteen differentially-expressed genes were found in relation to HBV-host interaction and some of them were enriched in interferon (IFN)-β pathway in LWWL-treated HepG2.2.15 cells. CD3+CD4+ T-cell frequency and serum IFN-γ were significantly increased in LWWL-treated mice compared to LWWL-untreated mice. Among 26 compounds with potential anti-HBV effects that were predicted by network pharmacology, four compounds (quercetin, luteolin, wogonin, and kaempferol) were experimentally confirmed to have antiviral potency. In conclusion, LWWL had potent inhibitory effect on both wild-type and entecavir-resistant HBV, which might be associated with increasing IFN-β and IFN-γ production.

The national Expanded Program on Immunization (EPI) in China has covered vaccines for measles, mumps, and rubella, among children aged 18–24 months since September 2008. However, no previous studies have quantified the effectiveness of the EPI on mumps incidence. There are methodological challenges in assessing the effect of an intervention that targets a subpopulation but finally influences the whole population. In this study, monthly data on mumps incidence were collected in Guangzhou, China, during 2005–2019. We proposed a multi-age-group interrupted time-series design, setting the starting time of exerting effect separately for 14 different age groups. A mixed-effects quasi-Poisson regression was applied to analyze the effectiveness of the EPI on mumps incidence, after controlling for long-term and seasonal trends, and meteorological factors. The model also accounted for the first-order autocorrelation within each age group. Between-age-group correlations were expressed using the contact matrix of age groups. We found that 70,682 mumps cases were reported during 2005–2019, with an annual incidence rate of 37.91 cases per 100,000 population. The effect of EPI strengthened over time, resulting in a decrease in the incidence of mumps by 16.6% (EPI-associated excess risk% = −16.6%, 95% CI: −27.0% to −4.7%) in September 2009 to 40.1% (EPI-associated excess risk% = −40.1%, 95% CI: −46.1% to −33.3%) in September 2019. A reverse U-shape pattern was found in age-specific effect estimates, with the largest reduction of 129 cases per 100,000 population (95% CI: 14 to 1173) in those aged 4–5 years. The EPI is effective in reducing the mumps incidence in Guangzhou. The proposed modeling strategy can be applied for simultaneous assessment of the effectiveness of public health interventions across different age groups, with adequate adjustment for within- and between-group correlations.

BackgroundSelf-management of ambulatory cancer pain is full of challenges. Motivated by the need for better pain management, we developed a WeChat-supported platform, Medication Housekeeper (MediHK), to enhance communication, optimize outcomes, and promote self-management in the home setting. ObjectiveWe conducted a randomized controlled trial to assess whether the joint physician-pharmacist team through MediHK would provide better self-management of ambulatory patients with cancer pain. MethodsPatients were randomly assigned to either an intervention group or control group. During the 4-week study period, the pharmacist would send 24-hour pain diaries daily, adverse drug reaction (ADR) forms every 3 days, and the Brief Pain Inventory form every 15 days to patients in the intervention group via MediHK. If a patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician, who was then responsible for prescribing or adjusting pain medications. If no adjustments were needed, the pharmacist provided appropriate targeted education based on knowledge deficits. Patients in the control group received conventional care and did not receive reminders to fill out the forms. However, if the control group patients filled out a form via MediHK, the pain management team would review and respond in the same way as for the intervention group. The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included patient-reported outcome measures, medication adherence, ADRs, and rehospitalization rates. ResultsA total of 100 patients were included, with 51 (51%) in the intervention group and 49 (49%) in the control group. The worst pain scores, least pain scores, and average pain scores in the intervention group and the control group were statistically different, with median values of 4 (IQR 3-7) vs 7 (IQR 6-8; P=.001), 1 (IQR 0-2) vs 2 (IQR 1-3; P=.02), and 2 (IQR 2-4) vs 4 (IQR 3-5; P=.001), respectively, at the end of the study. The pain interference on patients' general activity, mood, relationships with others, and interests was reduced, but the difference was not statistically significant compared with the control group (Ps=.10-.76). The medication adherence rate increased from 43% to 63% in the intervention group, compared with an increase of 33% to 51% in the control group (P

In 2019, dengue incidences increased dramatically in many countries. However, the prospective growth in dengue incidence did not occur in Guangzhou, China. We examined the effectiveness of early start of Grade III response to dengue in Guangzhou. We extracted the data on daily number of dengue cases during 2017-2019 in Guangzhou and weekly data for Foshan and Zhongshan from the China National Notifiable Disease Reporting System, while the data on weekly number of positive ovitraps for adult and larval Aedes albopictus were obtained from Guangzhou Center for Disease Control and Prevention. We estimated the number of dengue cases prevented by bringing forward the starting time of Grade III response from September in 2017-2018 to August in 2019 in Guangzhou using a quasi-Poisson regression model and applied the Baron and Kenny's approach to explore whether mosquito vector density was a mediator of the protective benefit. In Guangzhou, early start of Grade III response was associated with a decline in dengue incidence (relative risk [RR]: 0.54, 95% confidence interval [CI]: 0.43-0.70), with 987 (95% CI: 521-1,593) cases averted in 2019. The rate of positive ovitraps also significantly declined (RR: 0.64, 95% CI: 0.53-0.77). Moreover, both mosquito vector density and early start of Grade III response was significantly associated with dengue incidence after adjustment for each other. By comparing with the incidence in Foshan and Zhongshan where the Grade III response has not been taken, benefits from the response starting in August were confirmed but not if starting from September. Early start of Grade III response has effectively mitigated the dengue burden in Guangzhou, China, which might be partially through reducing the mosquito vector density. Our findings have important public health implications for development and implementation of dengue control interventions for Guangzhou and other locations with dengue epidemics.

Abstract Background Understanding genetic diversity of wild plant germplasm and the relationships between ecogeographic and genetic characteristics may provide insights for better utilizing and conserving genetic resources. Elymus tangutorum (Nevski) Hand.-Mazz, a cool-season hexaploid perennial, is an important pasture bunchgrass species used for forages and grassland restoration in Qinghai-Tibet Plateau and northwest China. In this study, 27 E. tangutorum accessions from diverse origins of western China were evaluated using AFLP markers in an effort to delve into the genetic relationships among them. The effects of eco-environmental factors and geographical isolation on the genetic diversity and population structure were also elucidated. Results On account of 554 polymorphic fragments amplified with 14 primer combinations, the mean values of some marker parameters including polymorphic information content, resolving power and marker index were 0.2504, 14.10 and 23.07, respectively, validating the high efficiency and reliability of the markers selected. Genetic dissimilarity index values among accessions ranged from 0.1024 to 0.7137 with a mean of 0.2773. STRUCTURE, UPGMA clustering and PCoA analyses showed that all accessions could be divided into the three main clusters; however, this results do not exactly coincide with geographic groups. We found medium differentiation (F ST = 0.162) between Qinghai-Tibet Plateau (QTP) and Xinjiang (XJC), and high differentiation (F ST = 0.188) among three Bayesian subgroups. A significant correlation (r = 0.312) between genetic and geographical distance was observed by Mantel test in the species level, while the weak correlation was detected between genetic and environmental distance for all accessions and most of geographical groups. In addition, a significant ecological influence of average annual precipitation on genetic distance was revealed in XJC group and the Bayesian subgroup A. Conclusion This study indicates that AFLP technique are a useful tool to measure genetic diversity in E. tangutorum, showing that geographical and environmental factors (especially precipitation) together, play a crucial role in genetic differentiation patterns. These findings underline the importance of local adaptation in shaping patterns of genetic variability and population structure in E. tangutorum germplasm collected in Western China.

LZ91 magnesium alloy extruded sheets were subjected to cold rolling. The microstructure and texture evolution were tracked using optical microscopy (OM) and X-ray diffraction (XRD). The α-Mg and β-Li phases were elongated along rolling direction (RD), contributing to the formation of a thin lamellar “sandwich” structure. This “sandwich” structure is favored for glissile dislocation of α-Mg phase during rolling. The α-Mg and β-Li phases are near Burgers orientation relationship, resulting in an unusual RD texture component in (0002) pole figure. Keywords: LZ91, Microstructure, Texture, Burgers orientation relationship

The specific recognition of T cell receptors (TCR) and peptides presented by human leukocyte antigens (pHLAs) is the core step for T cell triggering to execute anti-tumor activity. However, TCR assembly and soluble expression are challenging, which precludes the broad use of TCR in tumor therapy. Herein, we used heterodimeric Fc to assist in the correct assembly of TCRs to achieve the stable and soluble expression of several TCRs in mammalian cells, and the soluble TCRs enable us to yield novel bispecific T cell engagers (TCR/aCD3) through pairing them with an anti-CD3 antibody. The NY-ESO-1/LAGE-1 targeted TCR/aCD3 (NY-TCR/aCD3) that we generated can redirect naïve T cells to specific lysis antigen-positive tumor cells, but the potency of the NY-TCR/aCD3 was disappointing. Furthermore, we found that the activation of T cells by NY-TCR/aCD3 was mild and unabiding, and the activity of NY-TCR/aCD3 could be significantly improved when we replaced naïve T cells with pre-activated T cells. Therefore, we employed the robust T cell activation ability of staphylococcal enterotoxin C2 (SEC2) to optimize the activity of NY-TCR/aCD3. Moreover, we found that the secretions of SEC2-activated T cells can promote HLA-I expression and thus increase target levels, which may further contribute to improving the activity of NY-TCR/aCD3. Our study described novel strategies for soluble TCR expression, and the optimization of the generation and potency of TCR/aCD3 provided a representative for us to fully exploit TCRs for the precision targeting of cancers.

The development of therapeutic monoclonal antibodies through mouse immunization often originates drug candidates that are not cross-reactive to the mouse ortholog. In such cases, and particularly in oncology, drug efficacy studies are performed on human tumor xenografts or with "surrogate" anti-mouse ortholog antibodies if targeting tumor host cells. Safety assessment of drug candidate(s) is performed at a later development stage in healthy non-human primates. While the latter remains necessary before a drug advances into human subjects, it precludes evaluation of safety in disease conditions and drug de-risking during early development. Therefore, mouse models that allow concomitant evaluation of drug efficacy and safety are highly desirable. The C-X-C motif chemokine receptor 4 (CXCR4) is an attractive target for tumor-targeted and immuno-oncology therapeutics, with multiple mouse immunization-derived antibodies undergoing clinical trials. Given the pleiotropic role of CXCR4 in cancer biology, we anticipate continuous interest in this target, particularly in the testing of therapeutic combinations for immuno-oncology. Here, we describe the generation and validation of the first mouse knock-in of the whole coding region of human CXCR4. Homozygous human CXCR4 knock-in (hereafter designated as HuCXCR4KI) mice were viable and outwardly healthy, reproduced normally and nursed their young. The expression pattern of human CXCR4 in this model was similar to that of CXCR4 expression in normal human tissues. The human CXCR4 knock-in gene was expressed as a biologically active protein, thereby allowing normal animal development and adequate"homing" of leukocytes to the bone marrow. To further validate our model, we used an in vivo functional assay of leukocyte mobilization from bone marrow to peripheral blood by blocking CXCR4 signaling. Both an anti-human CXCR4 -specific blocking antibody and the small molecule CXCR4 inhibitor AMD3100 induced increased leukocyte counts in peripheral blood, whereas an anti-mouse CXCR4 -specific blocking antibody had no effect. This new mouse model is useful to evaluate efficacy and safety of anti-human CXCR4 -specific drugs as single agents or in combination therapies, particularly in the oncology, immuno-oncology, wound healing and chronic inflammation therapeutic areas.

The southern Ordos Basin has excellent petroleum exploration prospects. However, the tectono-thermal history and the controls on petroleum generation, accumulation and preservation conditions in southern basin are unclear. In this study, we analyzed the present geothermal field, paleo-geothermal gradient, maturity of the hydrocarbon source rocks, uplift and cooling process and tectono-thermal evolution history. In the study area, for the Ordovician, Permain and the Triassic strata, the present temperature is low (30-70 °C) in the southeastern area but high (80-140 °C) in the northwestern area. The paleogeothermal gradient varied from 24 °C/km to 30 °C/km with a heat flow of 58e69 mW/m2 (i.e., a medium-temperature basin). The paleo-temperatures are higher than the present temperatures and the maximum paleo-temperatures controlled the thermal maturity of the source rocks. The vitrinite reflectance (Ro) values of the Triassic strata are >0.7% and the thermal maturity reached the middlemature oil generation stage. The Ro values of the Permian-Ordovician strata are >1.8% and the thermal maturity reached the over-mature gas generation stage. The southern Ordos Basin has experienced the multiple tectonic events at the Late Ordovician Caledonian (452 Ma), Late Triassic (215 Ma), Late Jurassic (165-160 Ma), End-Early Cretaceous (110-100 Ma) and Cenozoic (since 40 Ma). A large-scale tectonothermal event occurred at the End-Early Cretaceous (110-100 Ma), which was controlled by lithospheric extension, destruction and thinning. This event led to the highest paleo-temperatures and thermal maturities and coeval with the peak period of petroleum generation and accumulation. The southern Ordos Basin has undergone rapid and large-scale uplift since the Late Cretaceous due to expansion of the northeastern margin of the Tibetan Plateau, uplift of the Qinling orogenic belt and thrust faulting in the Liupanshan tectonic belt. The southern Ordos Basin experienced tectonic overprinting that was strong in the south and weak in the north. The strongest overprinting occurred in the southwestern part of the basin. The large-scale uplift, denudation and faulting led to oil and gas loss from reservoirs. The petroleum generation, accumulation and preservation in the southern Ordos Basin were affected by deep lithospheric structures and the tectono-thermal evolution. This work provides a novel tectono-thermal perspective on the petroleum generation, accumulation and preservation condition of the southern Ordos Basin. [ABSTRACT FROM AUTHOR]

In order to improve the distance of 5th Generation (5G) Mobile Communication Technology) millimeter-wave outdoor point-to-point relay transmission, a 2-port Multiple Input Multiple Output (MIMO) antenna with high gain and low sidelobe level characteristics is designed at 39 GHz. The antenna is designed using the Taylor synthesis method and slotting technology to increase the antenna gain and lower the sidelobe level. Loading hollow T-shaped branches reduces the mutual coupling between MIMO antennas. The measured results are basically in line with the simulation ones. The results show that the bandwidth of the antenna is 38:1 ~ 39:3 GHz; the isolation degree is more than 50 dB; the antenna gain is 25.75 dBi at 39 GHz; the E-plane and H-plane sidelobe levels are -20:5 dB and -20 dB, respectively. Furthermore, the Envelope Correlation Coefficient (ECC) is less than 0.022; the Diversity Gain (DG) is more than 9.89; and the radiation efficiency reaches 90% in the working frequency band. Therefore, this antenna can be used as a long-distance relay antenna in 5G millimeter-wave communication system with high gain and low sidelobe level characteristics based on meeting the requirements of the MIMO antenna. [ABSTRACT FROM AUTHOR]