High-Safety Lithium-Ion Battery Separator with Adjustable Temperature Function Inspired by the Sugar Gourd Structure.

As the power core of an electric vehicle, the performance of lithium-ion batteries (LIBs) is directly related to the vehicle quality and driving range. However, the charge-discharge performance and cycling performance are affected by the temperature. Excessive temperature can cause internal short circuits and even lead to safety issues, such as thermal runaway. The separator plays a crucial role in protecting the battery from regular operation, preventing direct touch between the cathode and the anode while allowing the transport of lithium ions. In this study, we have designed a thermoregulating separator in the shape of calabash, which uses melamine-encapsulated paraffin phase change material (PCM) with a wide enthalpy (0-168.52 J g-1) to dissipate the heat generated inside the battery promptly. Under extra-long-use conditions, the heat emitted by the battery is absorbed by the PCM without causing a significant temperature rise that triggers thermal runaway. The PCM separator can effectively suppress the temperature increase caused by battery penetration. Due to the unique structure of the PCM, the battery is short-circuited; it can significantly delay the internal temperature rise of the battery and quickly dissipate the heat, which is consistent with the characteristics of natural calabash in nutrient absorption and water diffusion, improving the melting and heat storage efficiency of the PCM. The design of the phase change separator provides an effective reference for overheat protection and improved safety in lithium-ion batteries.

Trajectories of Intergenerational Emotional Closeness in Multi-Child Aging Families in China.

Intergenerational emotional closeness (IEC) in multi-child families manifests not only in the overall parent-child relationship but also by the extent of its within-family differentiation. This study aimed to identify distinct trajectories of collective IEC in multi-child families and to examine its potential associated factors. The study used four waves of the China Family Panel Studies (2010-2018). Based on a sample of 3474 older adults (age >60), growth mixture modelling and logistic regression were conducted. Two latent trajectory patterns of IEC were identified: increasingly tight-knit (93%) and persistently collectively ambivalent (7%). Compared to the latter trajectory, older adults who had a married/cohabiting partner, had better health and received support from all children, were more likely to have increasingly tight-knit trajectories of IEC. The study tells a story more about emotional cohesion between Chinese older adults and multiple offspring over time. Aging families experiencing persistently collectively ambivalent IEC deserve more attention.

Self-Assembly of Binderless MXene Aerogel for Multiple-Scenario and Responsive Phase Change Composites with Ultrahigh Thermal Energy Storage Density and Exceptional Electromagnetic Interference Shielding.

The severe dependence of traditional phase change materials (PCMs) on the temperature-response and lattice deficiencies in versatility cannot satisfy demand for using such materials in complex application scenarios. Here, we introduced metal ions to induce the self-assembly of MXene nanosheets and achieve their ordered arrangement by combining suction filtration and rapid freezing. Subsequently, a series of MXene/ K+/paraffin wax (PW) phase change composites (PCCs) were obtained via vacuum impregnation in molten PW. The prepared MXene-based PCCs showed versatile applications from macroscale technologies, successfully transforming solar, electric, and magnetic energy into thermal energy stored as latent heat in the PCCs. Moreover, due to the absence of binder in the MXene-based aerogel, MK3@PW exhibits a prime solar-thermal conversion efficiency (98.4%). Notably, MK3@PW can further convert the collected heat energy into electric energy through thermoelectric equipment and realize favorable solar-thermal-electric conversion (producing 206 mV of voltage with light radiation intensity of 200 mw cm-2). An excellent Joule heat performance (reaching 105 °C with an input voltage of 2.5 V) and responsive magnetic-thermal conversion behavior (a charging time of 11.8 s can achieve a thermal insulation effect of 285 s) for contactless thermotherapy were also demonstrated by the MK3@PW. Specifically, as a result of the ordered arrangement of MXene nanosheet self-assembly induced by potassium ions, MK3@PW PCC exhibits a higher electromagnetic shielding efficiency value (57.7 dB) than pure MXene aerogel/PW PCC (29.8 dB) with the same MXene mass. This work presents an opportunity for the multi-scene response and practical application of PCMs that satisfy demand of next-generation multifunctional PCCs.

Molecular surveillance of chloroquine resistance in Plasmodium vivax isolates from malaria cases in Yunnan Province of China using pvcrt-o gene polymorphisms.

BACKGROUND: The efficacy of chloroquine treatment for vivax malaria has been rarely evaluated due to a lack of an appropriate testing method. The objective of this study was to conduct molecular monitoring of chloroquine resistance in Plasmodium vivax strains from vivax malaria patients in Yunnan Province, focusing on the analysis of polymorphism in the P. vivax chloroquine resistance transporter protein orthologous gene (pvcrt-o). METHODS: In accordance with the principles of a cohort study, blood samples were collected from malaria cases diagnosed with a P. vivax mono-infection in Yunnan Province from 2020 to 2022. Segmental PCR was used to amplify the whole pvcrt-o gene in the blood samples and their products were subsequently sequenced. The sequencing data were arranged to obtain the full coding DNA sequence (CDS) as well as the gene's promoter region sequences. The CDSs were aligned with the reference sequence (XM_001613407.1) of the P. vivax SalI isolate to identify the mutant loci. RESULTS: From a total of 375 blood samples taken from vivax malaria cases, 272 both whole gene CDSs (1272-1275 bp) and promoter DNA sequences (707 bp) of pvcrt-o gene were obtained. Among the whole CDSs, there were 7 single nucleotide polymorphic sites in which c.7 A>G was the minor allele frequency (MAF) site with 4.4% (12/272) detection rate. The mutation detection rate showed a significant decrease from 9.8% (10/102) in 2020 to 1.1% (1/92) in 2021 and 1.3% (1/78) in 2022, indicating statistical significance (χ2 = 11.256, P < 0.05). Among the identified 12 haplotypes, the majority of which were wild type (75.7%; 206/272). These four mutant haplotypes (Hap_3, Hap_5, Hap_9, and Hap_10) were classified as "K10 insertion type" and accounted for 12.1% (33/272). The detection rate of Hap_3 increased from 1.0% (1/102) in 2020 to 13.0% (12/92) in 2021 and 14.1% (11/78) in 2022, indicating statistical significance. A total of 23.8% (65/272) of the samples exhibited 14 bp (bp) deletions in the promoter region, occurring most frequently in the wild type haplotype (Hap_1) samples at a rate of 28.6% (59/206). CONCLUSIONS: In recent years in Yunnan Province, a notable proportion of vivax malaria patients are infected by P. vivax strains with a "K10 insertion" and partial sequence deletions in the promoter region of the pvcrt-o gene, necessitating vigilance.

Characteristics of molecular markers associated with chloroquine resistance in Plasmodium vivax strains from vivax malaria cases in Yunnan Province, China.

BACKGROUND: Chloroquine (CQ) has been the preferred clinical treatment for vivax malaria in Yunnan Province since 1958, with over 300,000 patients. This study aimed to help make trend predictions regarding variations the in anti-malarial drug susceptibility of Plasmodium vivax distributed in Yunnan Province and effectively implement monitoring measures on the efficacy of anti-malarial drugs for vivax malaria. METHODS: Blood samples collected from patients with mono-P. vivax infections were employed in this study based on the principle of cluster sampling. The whole gene of P. vivax multidrug resistance 1 protein gene (pvmdr1) was amplified by nested-PCR techniques and the PCR amplification produce were sequenced by Sanger bidirectional sequencing. The mutant loci and haplotypes of coding DNA sequence (CDS) were identified by comparison with the reference sequence (NC_009915.1) of the P. vivax Sal I isolate. Parameters such as Ka/Ks ratio were calculated using MEGA 5.04 software. RESULTS: A total of 753 blood samples from patients infected with mono-P. vivax were collected, of which 624 blood samples yielded the full gene sequence (4392 bp) of the pvmdr1 gene, with 283, 140, 119, and 82 sequences from 2014, 2020, 2021 and 2022, respectively. A total of 52 single nucleotide polymorphic (SNP) loci were detected for the 624 CDSs, of which 92.3% (48/52), 34.6% (18/52), 42.3% (22/52), and 36.5% (19/52) SNPs were detected in 2014, 2020, 2021 and 2022, respectively. All of 624 CDSs were defined for a total of 105 mutant haplotypes, with CDSs of 2014, 2020, 2021, and 2022 containing 88, 15, 21, and 13 haplotypes, respectively. Of the 105 haplotypes, the threefold mutant haplotype (Hap_87) was the starting point for stepwise evolution, and the most drastic tenfold mutations were Hap_14 and Hap_78, and the fivefold, sixfold, sevenfold, and eightfold mutations. CONCLUSIONS: In the majority of vivax malaria cases in Yunnan Province, most of them were infected with strains carrying demonstrating highly mutated in pvmdr1 genes. However, the dominant mutation strains types varied from year to year, which warrants further exploration in order to confirm the correlation between with phenotypic changes in P. vivax strains and their susceptibility to anti-malarial drugs such as chloroquine.

Molecular identification of vivax malaria relapse patients in the Yunnan Province based on homology analysis of the Plasmodium vivax circumsporozoite protein gene.

More than 85% of the malaria burden in the Yunnan Province is caused by imported vivax malaria, and Yunnan is also where the majority of vivax malaria patients are diagnosed in China. Timely removal of the infection sources of Plasmodium vivax and its breeding environment remains the key to eliminating the secondary transmission of imported malaria. To that end, blood samples were collected from cases diagnosed and revalidated as single species infection with P. vivax in the Yunnan Province from 2013 to 2020. Specifically, samples from vivax malaria patients with suspected relapses episodes were subjected to PCR amplification, product sequencing, and analysis of the P. vivax circumsporozoite protein (pvcsp) gene. In total, 77 suspected relapse patients were identified out of 2484 cases infected with P. vivax, with a total of 81 recurrent episodes. A total of 156 CDS (coding DNA sequence) chains were obtained through PCR amplification and sequencing of the pvcsp gene from 159 blood samples, 121 of which can be matched to the paired sequences of 59 vivax malaria patients with both primary attack and recurrent experience. Of the 59 pairs of pvcsp gene sequences, every one of 31 pairs showed only one haplotype and no variant sites (VS), meaning every two paired sequence was completely homologous. Every one of the remaining 28 paired sequences had two haplotypes but no length polymorphism, indicating that the paired sequences was "weakly heterologous" with no fragment insertions (or deletions). All 59 vivax malaria patients with recurrences were caused by the activation of P. vivax hypnozoites originated from the same population as the primary infection. The paired analysis of the similarity between high variant genes allowed the identification of relapse episodes caused by P. vivax homologous hypnozoites and also demonstrated pvcsp gene as one of the candidate molecular markers for tracing infection origin.

Socio-economic determinants of suicide rates in transforming China: A spatial-temporal analysis from 1990 to 2015.

BACKGROUND: China has experienced dramatic social changes in the last three decades. This study aimed to investigate socio-economic factors related to suicide rates in China from 1990 to 2015, and examine how the impacts of these factors on suicide rates changed over time. METHODS: Suicide rates in 31 provinces in mainland China between 1990 and 2015 were obtained from the Global Burden of Disease (GBD) Study 2019. Temporal-spatial modelling was applied to assess the effects of GDP per capita, urbanization, migration, employment, divorce, proportions of children and older adults on provincial overall, male and female suicide rates. FINDINGS: The overall suicide rate in China declined from 18·1 /100,000 in 1990 to 8·6 /100,000 in 2015, with considerable spatial variation in the magnitude of decline across provinces. The protective effects of increasing in GDP per capita, and urbanization, on provincial suicide rate were strong in 1990 (log GDP: -3·56 [95% CI: -6·15, -0·96], urbanisation: -0·07 [-0·14, -0·01]), however these effects were negligible by 2015. The association between employment and suicide rates has shifted from positive to negative over the study period, while migration remained a constant risk factor for high suicide rates (0·04 [0.00, 0·09]). INTERPRETATION: This study highlighted the dynamic effects of economic and social factors on suicide rates in the context of transforming China. To maintain further reductions in suicide rates cannot rely simply on improving people's materialistic and economic conditions. A more holistic approach to improve overall population well-being is needed. FUNDING: Humanities and Social Sciences Prestigious Fellowship (37000320) and the General Research Fund (17611619) at the University of Hong Kong.

Intergenerational relationship quality and activity profiles among older adults in China.

Currently, very few studies have comprehensively investigated how intergenerational relationship quality (IRQ) between older parents and adult children is related to older adults' activity engagement. To fill this gap, this study endeavoured to examine the associations between IRQ and older adults' activity profiles, not only considering the overall IRQ but also different dimensions of IRQ. We also aimed to reveal the different roles of IRQ with son(s) and with daughter(s). This study made use of survey data collected in Yibin City, Sichuan Province of China in 2018 (N = 4,211). We adopted hierarchical cluster analysis to identify activity profiles, and performed multinomial logistic regressions to assess the association between IRQ and the profiles. We identified five activity profiles among older adults: "caregiving-oriented", "employment-oriented", "social withdrawal", "diverse engagement" and "physically active". Those with greater IRQ were more likely to be "caregiving-oriented" and have "diverse engagement" relative to "social withdrawal". It also showed that structural-associational solidarity and affectual closeness were more predictive of the activity profiles, compared to consensual-normative solidarity and intergenerational conflict. Children's gender plays an important role in the relationship between IRQ and activity engagement profiles. Good intergenerational relationships might not narrow down older adults' activity domains, and instead might actually promote their participation in diverse domains. Promoting structural-associational solidarity and affectual closeness was likely to reduce social withdrawal among older adults in China.

Prediction of the CYP2D6 enzymatic activity based on investigating of the CYP2D6 genotypes around the vivax malaria patients in Yunnan Province, China.

BACKGROUND: In recent years, the incidence rate of vivax malaria recurrence still had 3.1% in Yunnan Province population after eradication therapy using primaquine (PQ). In order to understand the specific failure reasons for preventing vivax malaria relapses, a preliminary exploration on the CYP2D6 enzyme activity was carried out in the vivax malaria patients in Yunnan Province population by analysing mutational polymorphism in the coding region of CYP2D6 gene. METHODS: Blood samples were collected from vivax malaria patients with suspected relapse (SR) and non-relapsed (NR) malaria in Yunnan Province. The DNA fragments containing 9 exons regions of human CYP2D6 gene were amplified by performing PCR and sequenced. The sequencing results were aligned by using DNAStar 11.0 to obtain the coding DNA sequence (CDS) of CYP2D6 gene. DnaSP 6.11.01 software was used to identify mutant polymorphisms and haplotypes of the CDS chain. The waterfall function of GenVisR package in R was utilized to visualize the mutational landscape. The alleles of CYP2D6 gene were identified according to the criteria prescribed by Human Cytochrome P450 (CYP) Allele Nomenclature Committee Database and the CYP2D6 enzyme activity was predicted based on diploid genotype. RESULTS: A total of 320 maternal CDS chains, including 63 from SR group and 257 from NR group, were obtained. Twelve mutant loci, including c.31 (rs769259), c.100 (rs1065852), c.271 (rs28371703), c.281 (rs28371704), c.294 (rs28371705), c.297 (rs200269944), c.336 (rs1081003), c.408 (rs1058164), c.505 (rs5030865), c.801 (rs28371718), c.886 (rs16947), and c.1,457 (rs1135840) were observed on the 640 CDS chains (including 320 maternal and 320 paternal chains). The high-frequency mutation at rs1135840 (0.703) and low-frequency mutation, such as rs28371703, were detected only in the SR group. The frequency of mutant rs1058164 and rs1135840 were significantly increased in the SR group ([Formula: see text]= 4.468, 5.889, P < 0.05), as opposed to the NR group. Of the 23 haplotypes (from Hap_1 to Hap_23), the nomenclatures of 11 allelic forms could be found: Hap_3 was non-mutant, Hap_2 accounted for the highest frequency (36.9%, 236/640), and Hap_9 had the most complex sequence structure, containing 7 loci mutations. Allele *10 was the most frequent among these genotypes (0.423). Among the allele *10 standard named genotypes, *1/*10, *1/*1 and *2/*10 were significantly more frequent in the NR group ([Formula: see text]= 3.911, P < 0.05) and all showed uncompromised enzyme activity; the impaired genotype *10/*39 was more frequent in the SR group ([Formula: see text]= 10.050, P < 0.05), and genotype *4/*4was detected only in the SR group. CONCLUSION: In the patients receiving PQ dosage in Yunnan Province population, both rs1135840 single nucleotide polymorphism and *10 allele form was common in the CYP2D6 gene. Low-frequency mutation sites, such as rs28371703, were only presented in patients with vivax malaria relapse.

The link between climate change, food security and fertility: The case of Bangladesh.

Climate change is likely to worsen the food security situation through its impact on food production, which may indirectly affect fertility behaviour. This study examines the direct and indirect effects of climate change (e.g., temperature and precipitation) via the production of major crops, as well as their short- and long-term effects on the total fertility rate (TFR) in Bangladesh. We used structural equation modelling (SEM) to perform path analysis and distinguish the direct influence of climate change on fertility and its indirect influence on fertility through food security. We also applied the error correction model (ECM) to analyze the time-series data on temperature and precipitation, crop production and fertility rate of Bangladesh from 1966 to 2015. The results show that maximum temperature has a direct effect and indirect negative effect-via crop production-on TFR, while crop production has a direct positive effect and indirect negative effect-via infant mortality-on TFR. In the short term, TFR responds negatively to the maximum temperature but positively in the long term. The effect of rainfall on TFR is found to be direct, positive, but mainly short-term. Although indicators of economic development play an important part in the fertility decline in Bangladesh, some climate change parameters and crop production are non-negligible factors.

The status of anxiety state among cancer patients and their relatives during coronavirus disease 2019 (COVID-19) in Hubei, China.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, tumor patients and their families might suffer from greater psychological stress as a result of anxiety or other psychological disorders. We conducted an online study during the epidemic to explore the mental state of tumor patients and their families during this extraordinary time. METHODS: A cross-sectional survey was carried out. Questionnaires were distributed through the WeChat "Questionnaire Star" network. The snowball sampling technique was adopted and further promoted by subjects who had completed the questionnaire. RESULTS: A total of 1,030 valid questionnaires were collected. There were 609 (59.13%) tumor patients and 421 (40.87%) family members. One hundred and fifty-six (15.15%) subjects had anxiety, among which 65 (6.31%) had moderate to severe anxiety. Single-factor analysis indicated that age (>60 years old), the farmer occupation, and a high sleep disorder assessment score were risk factors for anxiety, while the latter two might also be independent risk factors, as suggested by multi-factor analysis. Infrequent contact with doctors was an independent risk factor for cancer patients, while uninterrupted anti-tumor therapy was an independent protective factor. 40.19% of the subjects expressed a need for psychosocial support during the COVID-19 period. CONCLUSIONS: The COVID-19 outbreak resulted in tumor patients and their relatives experiencing greater psychological pressure than usual, and patients were more worried about anti-tumor treatment and disease progression impacted by the epidemic. Both groups had a significant need for psychosocial help.

The association of CYP2D6 gene polymorphisms in the full-length coding region with higher recurrence rate of vivax malaria in Yunnan Province, China.

BACKGROUND: Accumulating evidence suggest that compromised CYP2D6 enzyme activity caused by gene mutation could contribute to primaquine failure for the radical cure of vivax malaria. The current study aims to preliminarily reveal the association between the recurrence of vivax malaria in Yunnan Province and CYP2D6 gene mutation by analysing polymorphisms in the entire coding region of human CYP2D6 gene. METHODS: Blood samples were collected from patients with vivax malaria, who received "chloroquine and 8-day course of primaquine therapy" in Yunnan Province. The suspected relapsed cases were determined by epidemiological approaches and gene sequence alignment. PCR was conducted to amplify the CYP2D6 gene in the human genome, and the amplified products were then sequenced to compare with the non-mutation "reference" sequence, so as to ensure correct sequencing results and to determine 9 exon regions. Subsequently, the DNA sequences of 9 exons were spliced into the coding DNA sequence (CDS), which, by default, is known as maternal CDS. The paternal CDS was obtained by adjusting the bases according to the sequencing peaks. The mutation loci, haplotypes (star alleles), genotypes and odds ratios (OR) of all the CDSs were analysed. RESULTS: Of the119 maternal CDS chains in total with 1491 bp in length, 12 mutation sites in the 238 maternal and paternal CDS chains were detected. The c.408G > C mutation was most frequently detected in both suspected relapsed group (SR) and non-relapsed group (NR), reaching 85.2% (75/88) and 76.0% (114/150), respectively. The c.886C > T mutation was most closely related to the recurrence of vivax malaria (OR = 2.167, 95% CI 1.104-4.252, P < 0.05). Among the 23 haplotypes (Hap_1 ~ Hap_23), Hap_3 was non-mutant, and the sequence structure of Hap_9 was the most complicated one. Five star alleles, including *1, *2, *4, *10 and *39, were confirmed by comparison, and CYP2D6*10 allele accounted for the largest percentage (45.4%, 108/238). The frequency of CYP2D6*2 allele in the SR group was significantly higher than that in the NR group (Χ2 = 16.177, P < 0.05). Of the defined 24 genotypes, 8 genotypes, including *4/*4, *4/*o, *2/*39, *39/*m, *39/*x, *1/*r, *1/*n, and *v/*10, were detected only in the SR group. CONCLUSION: Mutation of CYP2D6*10 allele accounts for the highest proportion of vivax malaria cases in Yunnan Province. The mutations of c. 886C > T and CYP2D6*2 allele, which correspond to impaired PQ metabolizer phenotype, are most closely related to the relapse of vivax malaria. In addition, the genotype *4/*4 with null CYP2D6 enzyme function was only detected in the SR group. These results reveal the risk of defected CYP2D6 enzyme activity that diminishes the therapeutic effect of primaquine on vivax malaria.

Solid Tumor Complicated With Venous Thromboembolism: A 10-Year Retrospective Cross-Sectional Study.

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) occurs more frequently in cancer patients than in the general population. A retrospective cross-sectional study was carried out in patients with solid tumor complicated with VTE admitted to the Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 1st, 2008 and December 31th, 2017. The incidence of VTE in hospitalized cancer patients was 1.8%, twice the incidence of VTE in hospitalized non-cancer patients. The annual incidence of cancer-associated VTE in our center varied between 1.6% in 2015 and 0.4% in 2009 with an overall average incidence of 1.3% over the research decade. BMI values of 549(67.7%) cancer patients were within the normal range, but none of patients had BMI greater than 35 kg/m2. 747(92.1%) cancer patients had ECOG PS score ≤ 2 and 481(59.3%) had distant metastasis. Patients with pancreatic, bladder, ovarian and endometrial cancer had the highest incidence of VTE. Upper extremity DVT (47.2%) was more common in cancer patients and might be closely associated with CVC (74.9%), while lower extremities DVT (36.1%) intended to PE development (15.0%). The annual incidence rates showed a fluctuating and upward trend over the research decade. VTE occurrence was closely related to tumor stage, tumor site, catheterization and anti-neoplasm therapy in cancer patients.

A Decomposition of Life Expectancy and Life Disparity: Comparison Between Hong Kong and Japan.

BACKGROUND: Life expectancy and life disparity are 2 useful indicators to assess the health condition of a society. Both Hong Kong and Japan have one of the longest life expectancies in the world. Recently, Hong Kong has overtaken Japan and topped the life expectancy rankings. However, whether Hong Kong has also outperformed Japan in life disparity is still unknown. METHODS: Decomposition analyses have been conducted to evaluate age-specific contributions to the changes in life expectancy and life disparity for each of the populations. Furthermore, the differences between the 2 populations were examined over the period 1977-2016. RESULTS: Reduction in mortality of the adult and the old age groups contributes most to the increase in life expectancy for the study period. Hong Kong has a higher life disparity than Japan, and due to the great improvement in reducing premature deaths, the Hong Kong-Japan gap has been narrowing. However, in recent years, further reduction in mortality of the oldest elderly in Hong Kong has actually contributed to the increase in its disparity, thus widening its gap with Japan again. CONCLUSION: Increasing dominant influence of "saving lives at late ages" is very likely to cause the reemergence of increasing life disparity in these 2 long-lived populations.

Analysis of initial laboratory diagnosis of malaria and its accuracy compared with re-testing from 2013 to 2018 in Yunnan Province, China.

BACKGROUND: According to China's Malaria Eradication Action Plan, malaria cases diagnosed and reported by health authorities at the county level must be further re-confirmed by provincial laboratories. The Yunnan Province Malaria Diagnostic Reference Laboratory (YPMDRL) began the synchronous implementation of microscopic examinations and nested polymerase chain reaction (nested-PCR) testing to re-test the malaria cases initially diagnosed by county-level laboratories and to evaluate the consistency of Plasmodium species identified between by YPMDRL and by the county-level laboratories from 2013 to 2018 in Yunnan Province. METHODS: Data on malaria initial diagnosis completed by county-level laboratories in Yunnan Province were collected weekly from the "China Disease Prevention and Control Information System" from 2013 to 2018. The YPMDRL performed Plasmodium microscopic examination and 18S rRNA gene nested-PCR testing on every malaria case managed by the China Disease Prevention and Control Information System. The re-testing detection results were fed back to the initial diagnosis and reporting unit for revision of malaria case types. RESULTS: A total of 2,869 malaria cases were diagnosed and reported by county-level laboratories in Yunnan Province from 2013 to 2018. The re-testing rate was 95.6% (2,742/2,869), and the re-testing rate increased from 2013 to 2018. Among the re-tested 2,742 cases, 96.7% (2651/2742), 2.2% (59/2742), and 1.1% (32/2742) were doubly examined by microscopy and by nested-PCR, only by microscopy, and only by nested-PCR, respectively. The total Plasmodium species accuracy rate at county-level laboratories was 92.6% (2,543/2,742) reference to the diagnosis by YPMDRL. Among the inconsistent 199 cases, they were identified as including 103 negative cases, 45 falciparum malaria cases, 30 vivax malaria cases, 11 ovale malaria cases, and 10 malariae malaria cases by YPMDRL. From 2013 to 2018, the revised and registered malaria cases by the China Disease Prevention and Control Information System in Yunnan Province was 2,747 cases, including 2,305 vivax malaria cases, 421 falciparum malaria cases, 11 ovale malaria cases, and 10 malariae malaria cases. CONCLUSIONS: The double re-testing strategy by microscopy and by gene testing increases the accuracy of diagnoses malaria in Yunnan Province, and gene testing can reliably differentiate Plasmodium species. The re-testing results provided by YPMDRL are the authoritative basis for revising malaria kind in Yunnan Province.

Polymorphism analysis of propeller domain of k13 gene in Plasmodium ovale curtisi and Plasmodium ovale wallikeri isolates original infection from Myanmar and Africa in Yunnan Province, China.

BACKGROUND: Eighteen imported ovale malaria cases imported from Myanmar and various African countries have been reported in Yunnan Province, China from 2013 to 2018. All of them have been confirmed by morphological examination and 18S small subunit ribosomal RNA gene (18S rRNA) based PCR in YNRL. Nevertheless, the subtypes of Plasmodium ovale could not be identified based on 18S rRNA gene test, thus posing challenges on its accurate diagnosis. To help establish a more sensitive and specific method for the detection of P. ovale genes, this study performs sequence analysis on k13-propeller polymorphisms in P. ovale. METHODS: Dried blood spots (DBS) from ovale malaria cases were collected from January 2013 to December 2018, and the infection sources were confirmed according to epidemiological investigation. DNA was extracted, and the coding region (from 206th aa to 725th aa) in k13 gene propeller domain was amplified using nested PCR. Subsequently, the amplified products were sequenced and compared with reference sequence to obtain CDS. The haplotypes and mutation loci of the CDS were analysed, and the spatial structure of the amino acid peptide chain of k13 gene propeller domain was predicted by SWISS-MODEL. RESULTS: The coding region from 224th aa to 725th aa of k13 gene from P. ovale in 83.3% of collected samples (15/18) were amplified. Three haplotypes were observed in 15 samples, and the values of Ka/Ks, nucleic acid diversity index (π) and expected heterozygosity (He) were 3.784, 0.0095, and 0.4250. Curtisi haplotype, Wallikeri haplotype, and mutant type accounted for 73.3% (11/15), 20.0% (3/15), and 6.7% (1/15). The predominant haplotypes of P. ovale curtisi were determined in all five Myanmar isolates. Of the ten African isolates, six were identified as P. o. curtisi, three were P. o. wallikeri and one was mutant type. Base substitutions between the sequences of P. o. curtisi and P. o. wallikeri were determined at 38 loci, such as c.711. Moreover, the A > T base substitution at c.1428 was a nonsynonymous mutation, resulting in amino acid variation of T476S in the 476th position. Compared with sequence of P. o. wallikeri, the double nonsynonymous mutations of G > A and A > T at the sites of c.1186 and c.1428 leads to the variations of D396N and T476S for the 396th and 476th amino acids positions. For P. o. curtisi and P. o. wallikeri, the peptide chains in the coding region from 224th aa to 725th aa of k13 gene merely formed a monomeric spatial model, whereas the double-variant peptide chains of D396N and T476S formed homodimeric spatial model. CONCLUSION: The propeller domain of k13 gene in the P. ovale isolates imported into Yunnan Province from Myanmar and Africa showed high differentiation. The sequences of Myanmar-imported isolates belong to P. o. curtisi, while the sequences of African isolates showed the sympatric distribution from P. o. curtisi, P. o. wallikeri and mutant isolates. The CDS with a double base substitution formed a dimeric spatial model to encode the peptide chain, which is completely different from the monomeric spatial structure to encode the peptide chain from P. o. curtisi and P. o. wallikeri.

Optimal Strategies for Reducing Number of People in the Social Security System.

Providing social security to the population in need has become a major expenditure for many governments. Reducing the number of dependents in the social security system and maintaining a dynamic economically active population is a high priority concern for policymakers. A good understanding of the dynamics of the social security system-specifically, who enters and who exits the system-would be helpful for formulating effective interventions. Here, we made use of the data of Hong Kong's Comprehensive Social Security Assistance (CSSA), which is currently a basic welfare scheme in Hong Kong that provides supplementary payments to households that cannot support themselves financially. We proposed a stochastic model to examine the in- and out- movement in the CSSA scheme and conducted elasticity analyses. The elasticity analyses allowed us to identify the potential target groups of people that would lead to the largest reduction in the number of the CSSA recipients in the system. This analytical method can also reveal whether policies would be more effective in preventing people from entering the CSSA system or helping them leave the CSSA scheme. Our analyses suggest that targeting those aged 30-49 with children would have the largest impact. Additionally, we found that policies that aim to prevent this group from entering the CSSA system would be more effective in reducing the number of CSSA recipients compared with policies that aim to help them exit. In contrast, for the younger age group of 10-29, policies that help them leave CSSA would be more effective than policies that prevent them from entering CSSA. Providing employment for those unemployed in this younger group would be more effective. The results indicate that by tailoring measures to specific subgroups, the overall number of CSSA recipients would be reduced, thereby improving the efficiency of Hong Kong's social security system, which has accounted for more than 16.5% of Hong Kong government expenditure in 2018, amounting to more than HKD 92 billion.

Combined Antiangiogenic Therapy and Immunotherapy Is Effective for Pancreatic Cancer With Mismatch Repair Proficiency but High Tumor Mutation Burden: A Case Report.

Immunotherapy has been recommended as a second-line treatment only for high microsatellite instability or DNA mismatch repair deficiency advanced pancreatic cancer in National Comprehensive Cancer Network guidelines. Here, we report a case with a good response to immunotherapy in pancreatic cancer with mismatch repair proficiency. A 55-year-old woman diagnosed with pancreatic cancer cT4N1M1 (liver, lung) who harbored ERBB2 mutations with high tumor mutation burden (TMB) underwent multiple therapies and survived 19 months. A partial response in pancreatic cancer was observed when the patient was treated with combined antiangiogenic therapy and immunotherapy after a series of ineffective treatments. Neutrophil-to-lymphocyte ratio (NLR), a predictive marker of efficacy of immunotherapy, confirmed that immunotherapy resulted in the partial response in pancreatic cancer. To our knowledge, this is the first to report advanced pancreatic cancer with mismatch repair proficiency had a good response to immunotherapy, and this is the first to report an association between high blood-based TMB or NLR and improved clinical outcomes in pancreatic cancer. Therefore, TMB may also be a biomarker for immunotherapy of pancreatic cancer, and NLR may be a prospective predictive marker for efficacy of immunotherapy in pancreatic cancer.

Validation and Application of the Chinese Version of the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI-C).

OBJECTIVES: To validate and use the Chinese Version of the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI-C) to assess the symptom burden of Chinese-speaking patients with gastrointestinal cancer. METHODS: In total, 527 patients with postoperative or advanced digestive tract tumors were enrolled in the trial, who had definitive diagnoses and different treatments in our cancer center. MDASI-GI-C was administered to these patients between February and December 2017. The item-scale correlations and internal consistency were evaluated. Construct validity was established by factor analysis. Hierarchical cluster analysis was performed. RESULTS: Cronbach's alpha of the symptom severity and interference subscales was 0.842 and 0.859, respectively. Construct validity revealed a four-factor structure. Known-group validity was established by comparing the MDASI-GI-C scores between patients having different Karnofsky Performance Status scores (≤70 or >70), which were observed to have significant differences. The overall mean subscale scores for the core and interference subscales were 1.63 ± 2.02 and 2.17 ± 2.34, respectively. Fatigue, disturbed sleep, and lack of appetite had the highest scores for most serious symptoms. No significant differences in age, working status, and educational level were found. CONCLUSIONS: MDASI-GI-C is a reliable and valid tool for assessing cancer-related symptoms in Chinese-speaking patients with digestive tract tumors, facilitates the understanding of the common symptoms of patients with digestive tract tumors, and enables timely management of these symptoms. Cognitive debriefing demonstrated that the patients found MDASI-GI-C to be an easy-to-use and understandable instrument.

Genetic polymorphism of histidine rich protein 2 in Plasmodium falciparum isolates from different infection sources in Yunnan Province, China.

BACKGROUND: Failed diagnoses of some falciparum malaria cases by RDTs are constantly reported in recent years. Plasmodium falciparum histidine-rich protein 2 (pfhpr2) gene deficiency has been found to be the major reason of RDTs failure in many countries. This article analysed the deletion of pfhpr2 gene of falciparum malaria cases isolated in Yunnan Province, China. METHODS: Blood samples from falciparum malaria cases diagnosed in Yunnan Province were collected. Plasmodium genomic DNA was extracted and the pfhrp2 gene exon2 region was amplified via nested PCR. The haplotype of the DNA sequence, the nucleic acid diversity index (PI) and expected heterozygosity (He) were analyzed. Count PfHRP2 amino acid peptide sequence repeat and its times, and predict the properties of PfHRP2 peptide chain reaction to RDTs testing. RESULTS: A total of 306 blood samples were collected, 84.9% (259/306) from which pfhrp2 PCR amplification products (gene exon2) were obtained, while the remaining 47 samples were false amplification. The length of the 250 DNA sequences ranged from 345 - 927 bp, with 151 haplotypes, with PI and He values of 0.169 and 0.983, respectively. The length of the PfHRP2 peptide chain translated from 250 DNA sequences ranged from 115 to 309 aa. All peptide chains had more than an amino acid codon deletion. All 250 PfHRP2 strands ended with a type 12 amino acid repeat, 98.0% (245/250) started with a type 1 repetition and 2.0% (5/250) with a type 2 repetition. The detection rate for type 2 duplicates was 100% (250/250). Prediction of RDT sensitivity of PfHRP2 peptide chains based on type 2 and type 7 repeats showed that 9.60% (24/250), 50.0% (125/250), 13.20% (33/250) and 27.20.5% (68/250) of the 250 peptide chains were very sensitive, sensitive, borderline and non-sensitive, respectively. CONCLUSION: The diversified polymorphism of the pfhrp2 gene deletion from different infection sources in the Yunnan province are extremely complex. The cause of the failure of pfhrp2 exon2 amplification is still to be investigated. The results of this study appeal to Yunnan Province for a timely evaluation of the effectiveness and applicability of RDTs in the diagnosis of malaria.