[Comparison of the Prognostic Value of C-Reactive Protein to Albumin Ratio and Glasgow Prognostic Score in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow prognostic score (GPS), in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed. A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical, laboratory data and follow-up information were included. The receiver operating characteristic (ROC) curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival. Furthermore, the association between CAR and baseline clinical, laboratory characteristics of patients was evaluated, and progression-free survival (PFS) and overall survival (OS) were compared between different CAR and GPS subgroups. Finally, the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes. RESULTS: ROC curve showed that the area under the curve (AUC) of CAR predicting PFS and OS in DLBCL patients was 0.687 (P =0.002) and 0.695 (P =0.005), respectively, with the optimal cut-off value of 0.11 for both predicting PFS and OS. Compared with the lower CAR (<0.11) group, the higher CAR (≥0.11) group had more clinical risk factors, including age >60 years (P =0.025), ECOG score ≥2 (P =0.004), Lugano stage III-IV (P < 0.001), non-germinal center B-cell-like (non-GCB) subtype (P =0.035), elevated lactate dehydrogenase (LDH) ( P < 0.001), extranodal involved site >1 (P =0.004) and IPI score >2 (P < 0.001). The interim response evaluation of patients showed that the overall response rate (ORR) and complete response rate (CRR) in the lower CAR group were both significantly better than those in the higher CAR group (ORR: 96.9% vs 80.0%, P =0.035; CRR: 63.6% vs 32.5%, P =0.008). With a median follow-up of 24 months, patients with lower CAR had significantly longer median PFS and OS than those with higher CAR (median PFS: not reached vs 67 months, P =0.0026; median OS: not reached vs 67 months, P =0.002), while there was no statistical difference in PFS (P =0.11) and OS (P =0.11) in patients with GPS of 0, 1, and 2. Multivariate Cox regression analysis indicated that only sex (male) and IPI score >2 were independent risk factors for both PFS and OS. CONCLUSION: CAR is significantly correlated with disease progression and survival in DLBCL patients; And compared with GPS, CAR has more advantages in predicting disease outcomes in DLBCL patients.

A case of fatal poisoning caused by etomidate: evidence from pathological and toxicological analyses.

Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.

Gaps in forensic toxicological analysis: The veiled abrin.

Abrus precatorius is an herbaceous, flowering plant that is widely distributed in tropical and subtropical regions. Its toxic component, known as abrin, is classified as one of the potentially significant biological warfare agents and bioterrorism tools due to its high toxicity. Abrin poisoning can be utilized to cause accidents, suicides, and homicides, which necessitates attention from clinicians and forensic scientists. Although a few studies have recently identified the toxicological and pharmacological mechanisms of abrin, the exact mechanism remains unclear. Furthermore, the clinical symptoms and pathological changes induced by abrin poisoning have not been fully characterized, and there is a lack of standardized methods for identifying biological samples of the toxin. Therefore, there is an urgent need for further toxicopathologic studies and the development of detection methods for abrin in the field of forensic medicine. This review provides an overview of the clinical symptoms, pathological changes, metabolic changes, toxicologic mechanisms, and detection methods of abrin poisoning from the perspective of forensic toxicology. Additionally, the evidence on abrin in the field of forensic toxicology and forensic pathology is discussed. Overall, this review serves as a reference for understanding the toxicological mechanism of abrin, highlighting the clinical applications of the toxin, and aiding in the diagnosis and forensic identification of toxin poisoning.

Changes in microbial composition and interaction patterns of female urogenital tract and rectum in response to HPV infection.

BACKGROUND: Previous studies have shown that changes in the microbial community of the female urogenital tract are associated with Human papillomavirus (HPV) infection. However, research on this association was mostly focused on a single site, and there are currently few joint studies on HPV infection and multiple sites in the female urogenital tract. METHODS: We selected 102 healthy women from Yunnan Province as the research object, collected cervical exfoliation fluid, vaginal, urethral, and rectal swabs for microbial community analysis, and measured bacterial load, and related cytokine content. The link between HPV, microbiota, and inflammation was comprehensively evaluated using bioinformatics methods. FINDINGS: The impact of HPV infection on the microbial composition of different parts varies. We have identified several signature bacterial genera that respond to HPV infection in several detection sites, such as Corynebacterium, Lactobacillus, Campylobacter, and Cutibacterium have been detected in multiple sites, reflecting their potential significance in cross body sites HPV infection responses. There was a solid microbial interaction network between the cervix, vagina, and urethra. The interrelationships between inflammatory factors and different bacterial genera might also affect the immune system's response to HPV infection. INTERPRETATION: It might be an effective strategy to prevent and treat HPV infection by simultaneously understanding the correlation between the microbial changes in multiple parts of the female urogenital tract and rectum and HPV infection, and controlling the microbial network related to HPV infection in different parts.

Mid-infrared dual-comb spectroscopy for rapid temperature distribution characterization.

Due to the influence of chemical reactions, phase change, and other phenomena, the combustion system is a complicated high-temperature environment. Therefore, the spatio-temporally resolved monitoring of the temperature field is crucial for gaining a comprehensive understanding of the intricate combustion environment. In this study, we proposed a fast and high-precision temperature measurement technique based on mid-infrared (MIR) dual-comb spectroscopy with a high spectral resolution and fast refresh rate. Based on this technique, the spatio-temporally resolved measurement of a non-uniform temperature field was achieved along the laser path. To verify the capability of DCS for temperature measurement, the bandhead ro-vibrational lines of the CO2 molecule were acquired, and the 1-σ uncertainty of the retrieved temperature was 3.2°C at 800°C within 100 ms. The results demonstrate the potential of our fast and high-precision laser diagnostic technique which can be further applied to combustion kinetics.

Application of acoustic spectroscopy and neural networks to on-line size measurement of pharmaceutical nanocrystals.

Acoustic spectroscopy and neural networks (NNs) are applied to on-line real-time measurement of particle size distribution (PSD) during wet milling of pharmaceutical nanocrystals. A method for modeling the relationship between acoustic attenuation spectra and PSD is proposed that is based on NNs and principal component analysis (PCA). PCA reduces the dimensions of both the spectra and the PSD; then, a neural network model of 2 × 2 × 2 (input, hidden, output layer nodes) with only eight connection weights is built. Compared with previous instrument models that could require as many as 14 physical properties, the current approach does not need any prior knowledge of the system's properties. In addition, the time taken to complete a PSD measurement is reduced from minutes to seconds and it always generates a single solution, rather than possible multiple PSD solutions as in early methods. Application to hydrotalcite nanomilling found good agreement between the on-line measurements and off-line analysis.

Penumbra-targeted CircOGDH siRNA-loaded nanoparticles alleviate neuronal apoptosis in focal brain ischaemia.

BACKGROUND: Nanoparticles (NPs) are a class of substances that can be loaded with therapeutic agents delivered to specific areas. In our earlier research, we identified a neuron-derived circular RNA (circRNA), circular oxoglutarate dehydrogenase (CircOGDH), as a promising therapeutic target for acute ischaemic stroke. This study dedicated to explore a prospective preliminary strategy of CircOGDH-based NP delivered to the ischaemic penumbra region in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. METHODS: Immunofluorescence in primary cortex neurons and in vivo fluorescence imaging revealed endocytosis of Poly(lactide-co-glycolide) (PLGA) poly amidoamine(PAMAM)@CircOGDH small interfering RNA (siRNA) NPs. Western blotting analysis and CCK8 assay were performed to evaluate the apoptotic level in ischaemic neurons treated with PLGA-PAMAM@CircOGDH siRNA NPs. Quantitative reverse transcription PCR experiments, mice behaviour test, T2 MRI analysis, Nissl and TdT-mediated dUTP nick end labeling (TUNEL) co-staining were performed to evaluate the apoptosis level of ischaemic penumbra neurons in MCAO/R mice. Biosafety evaluation of NPs in MCAO/R mice was detected by blood routine examination, liver and kidney function examination and HE staining. RESULTS: PLGA-PAMAM@CircOGDH siRNA NPs were successfully assembled. Endocytosis of PLGA-PAMAM@CircOGDH siRNA NPs in ischaemic neurons alleviated neuronal apoptotic level in vitro and in vivo. Furthermore, mice behaviour test showed that the neurological defects of MCAO/R mice were significantly alleviated after the tail injection of PLGA-PAMAM@CircOGDH siRNA NPs, and no toxic effects were observed. CONCLUSION: In conclusion, our results suggest that PLGA-PAMAM@CircOGDH siRNA NPs can be delivered to the ischaemic penumbra region and alleviate neuron apoptosis in MCAO/R mice and in ischaemic neurons; therefore, our study provides a desirable approach for using circRNA-based NPs for the treatment of ischaemic stroke.

[Prognostic Value of Pre-treatment Albumin/Fibrinogen Ratio in Patients with Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. RESULTS: The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR PFS=2.047, P =0.039; HR OS=4.854, P =0.001). CONCLUSION: Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.

Descriptive analyses of differentially expressed proteins during intrapuparial stage based on the label-free proteomics technique between Chrysomya megacephala and Synthesiomyia nudiseta.

The lack of rapid and accurate species identification methods on pupae restricts the practical application of forensic entomology. It is a new idea to construct portable and rapid identification kits based on the principle of antigen/antibody interaction. Screening differentially expressed proteins (DEPs) of fly pupae is a basis of solving the problem. Here, we used the label-free proteomics technique to discover the DEPs and further validate using the parallel reaction monitoring technique (PRM) in the common flies. In this study, we reared the Chrysomya megacephala and Synthesiomyia nudiseta at constanttemperature, and then we sampled at least four pupae at 24 h intervals until the end of the intrapuparial stage. We found 132 DEPs between Ch. megacephala, and S. nudiseta groups, with 68 and 64 proteins being up-regulated and down-regulated between the two groups. Among the 132 DEPs, we selected five proteins having potential for further development and utilization, such as C1-tetrahydrofolate synthase, Malate dehydrogenase, Transferrin, Protein disulfide-isomerase, and Fructose-bisphosphate aldolase, for further validation using PRM-targeted proteomics, with the trends of PRM results being consistent with the label-free data for corresponding proteins. The present study investigated DEPs via the label-free technique during the pupal development in the Ch. megacephala, and S. nudiseta and provided reference data for development of rapid and accurate identification kits.

Investigation and Analysis of Risk Factors and Psychological Status of Chronic Obstructive Pulmonary Disease in Permanent Residents Aged 40 or Older in Hongyuan County, Aba Prefecture, Sichuan Province.

Background: COPD is an important public health problem worldwide, and there is a lack of epidemiological data on COPD in high-altitude areas in Sichuan province. Thus, we aimed to investigate the prevalence, risk factors and psychological status of COPD in Hongyuan County, Aba Prefecture, Sichuan Province, which is located at an average altitude of 3507 meters. Methods: The 40 years old or greater permanent residents of Hongyuan County were selected by random sampling method, and the lung function test and questionnaires were conducted to determine the disease situation of COPD. The prevalence of COPD was compared among different factors of investigation, and multivariate logistic regression analysis was used for different factors to determine the independent influencing factors of COPD disease. Results: A total of 456 permanent residents aged 40 years or older in Hongyuan County, 436 qualified for quality control, among which 53 cases confirmed COPD, the total prevalence was 12.16%, among which the prevalence was 14.55% for men and it was 8.07% for women. There were significant differences in different gender, ethnicity, age, smoking status, smoking years, educational level, heating style, history of tuberculosis, and prevalence of BMI (P <0.05). Binary logistic regression analysis showed that age ≥60 years (OR = 2.810, 95% CI: 1.0457.557), Han Nationality (OR: 3.238, 95% CI: 1.290-8.127), the heating method including biofuels (OR: 18.119, 95% CI: 4.140-79.303) and coals (OR: 6.973, 95% CI: 1.856-26.200), medical history of pulmonary tuberculosis (OR: 2.670, 95% CI: 1.278-5.578), the education level including junior high school (OR: 3.336, 95% CI: 1.2259.075), high school and above (OR: 5.910, 95% CI: 1.796-19.450), and smoking (OR: 10.774, 95% CI: 3.622-32.051) were independent risk factors for COPD disease. The prevalence of anxiety was 16.98%, and the prevalence of depression was 13.2%. Conclusion: The prevalence of COPD in Hongyuan County was higher than the national level; age, ethnic group, education, smoking, heating method, and history of tuberculosis are the independent influencing factors of COPD in Hongyuan County. The prevalence of anxiety and depression is low.

Dual-comb optical activity spectroscopy for the analysis of vibrational optical activity induced by external magnetic field.

Optical activity (OA) spectroscopy is a powerful tool to characterize molecular chirality, explore the stereo-specific structure and study the solution-state conformation of biomolecules, which is widely utilized in the fields of molecular chirality, pharmaceutics and analytical chemistry. Due to the considerably weak effect, OA spectral analysis has high demands on measurement speed and sensitivity, especially for organic biomolecules. Moreover, gas-phase OA measurements require higher resolution to resolve Doppler-limited profiles. Here, we show the unmatched potential of dual-comb spectroscopy (DCS) in magnetic optical activity spectroscopy (MOAS) of gas-phase molecules with the resolution of hundred-MHz level and the high-speed measurement of sub-millisecond level. As a demonstration, we achieved the rapid, high-precision and high-resolution MOAS measurement of the nitrogen dioxide [Formula: see text]+[Formula: see text] band and the nitric oxide overtone band, which can be used to analyze fine structure of molecules. Besides, the preliminary demonstration of liquid-phase chiroptical activity (as weak as 10-5) has been achieved with several seconds of sampling time, which could become a routine approach enabling ultrafast dynamics analysis of chiral structural conformations.

Microstructural Evolution of SK85 Pearlitic Steel Deformed by Heavy Cold Rolling.

The microstructural evolution of SK85 pearlitic steel cold-rolled up to a 90% rolling reduction was characterized by scanning electron microscopy with electron backscattered diffraction (EBSD) and X-ray diffraction (XRD). SK85 steel exhibits excellent cold rolling performance. The interlamellar spacing of pearlite is refined obviously and a tensile strength of 2318 MPa can be reached for SK85 steel after 90% rolling reduction, an increase of 83% from 1264 MPa before rolling. The EBSD observation indicates that the {001} <110> texture becomes pronounced at a 90% rolling reduction in cold-rolled Sk85 steel. A propagation and multiplication of dislocations occur during rolling as the kernel average misorientation (KAM) angles significantly increase from 0.72° to 2.11°. The XRD analysis reveals that bcc ferrite is transformed into a bct structure at a 90% rolling reduction. The strengthening mechanism was discussed.

Population genetics and forensic efficiency of 30 InDel markers in four Chinese ethnic groups residing in Sichuan.

Sichuan Province is located at the transitional junction regions of the Qinghai-Tibet Plateau and the low-altitude plains. It also serves as the corridor of Sino-Tibetan-speaking population migration and expansion since neolithic expansion of Proto-Tibeto-Burman populations from Middle/Upper Yellow River during Majiayao period (3300-2000 BC). However, the population structure and the corresponding genetic diversity of forensic-related markers in this region remain unclear. Thus, we genotyped 30 insertion-deletion (InDel) markers in 444 samples from four ethnic groups (Han, Tibetan, Hui and Yi) from Sichuan Province using the Investigator® DIPplex kit to explore the characteristics of population genetics and forensic genetic focuses. All the loci were found to be in Hardy-Weinberg Equilibrium (HWE) after applying a Bonferroni correction and no pairwise loci showed prominent linkage disequilibrium. The combined matching probability (CMP) and the combined power of discrimination (CPD) are larger than 1.8089 × 10-11 and 0.99999999995, respectively. Principal component analysis, multi-dimensional scaling plots and Neighbour-Joining tree among 65 worldwide populations indicated that Sichuan Hui and Han are genetically close to Hmong-Mien and Tai-Kadai-speaking populations, and Sichuan Tibetan and Yi bear a strong genetic affinity with Tibeto-Burman-speaking populations. The model-based genetic structure further supports the genetic affinity between the studied populations and linguistically close populations.Key PointsForensic parameters of 30 insertion-deletions (InDels) in 444 individuals from four populations are reported, which showed abundant genetic affinity and diversity among populations and high value in personal identification.Genetic similarities existed between the studied populations and ethnically, linguistically close populations.Sichuan Hui and Han are genetically close to Hmong-Mien and Tai-Kadai-speaking populations.Sichuan Tibetan and Yi bear a strong genetic affinity with Tibeto-Burman-speaking populations.

Quantitative analysis for detection and grading of hepatocellular carcinoma: Comparison of diffusion kurtosis imaging, intravoxel incoherent motion and conventional diffusion-weighted imaging.

The aim of the present study was to compare the diagnostic performance of the main parameters derived from diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI) regarding the detection and grading of hepatocellular carcinoma (HCC). A total of 78 patients diagnosed with HCC by biopsy were prospectively enrolled in the present study, and underwent routine magnetic resonance imaging (MRI), DWI, IVIM, DKI and contrast-enhanced MRI prior to surgery. Measurements, including mean diffusivity (MD), mean diffusional kurtosis (MK), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC), were compared with grading HCC using one-way ANOVA followed by the Student-Neuman-Keuls-q post-hoc test. Spearman's correlation coefficient was used to analyze the correlation between each parameter and pathological grade, while the diagnostic efficiency was evaluated using a receiver operating characteristic (ROC) curve. The 78 patients enrolled in the present study were grouped into highly (n=22), moderately (n=41) or poorly (n=15) differentiated HCC groups according to the criteria of Pathology and Genetics Tumors of the Digestive System. MK values differed significantly between different grades and decreased gradually with the degree of tumor differentiation. The MD, D and ADC values in the highly differentiated HCC group were significantly higher than those in the moderately or poorly differentiated HCC groups (all P<0.001), whereas no significant differences were observed in D* or f (P=0.502 and P=0.853, respectively). A significant correlation was observed between MK, MD, D and ADC, and HCC grades (r=0.705, r=0.570, r=0.423 and r=0.687, respectively). The comparison of the ROC curves of MK, MD, D, ADC, D* and f values for predicting highly differentiated HCC suggested that MK and D were the best indicators for predicting highly differentiated HCC, as the area under the ROC curve (AUC) of MK and D was significantly higher than that of ADC (Z=2.247 and 2.428, P=0.025 and 0.016, respectively), whereas non-statistically significant differences were observed in the AUC values between MK and D (Z=0.072; P=0.942). The DKI-derived MK and IVIM-derived D values had a similar diagnostic performance and were superior to ADC in discriminating the histological grade of HCC. In addition, the combination of MK and D values exhibited an improved diagnostic performance.

Comparative study of Janus B2XY (X, Y = S, Se, Te) and F-BNBN-H monolayers for water splitting: revealing the positive and negative roles of the intrinsic dipole.

It is widely recognized that the intrinsic dipole in two-dimensional (2D) photocatalysts promotes hydrogen production during water splitting. Herein, we wonder whether the intrinsic dipole plays a negative role in water splitting. In this work, we make a comparative study of the structural, electronic, and photocatalytic properties of Janus B2XY (X, Y = S, Se, Te) and F-BNBN-H monolayers using first principles. Our theoretical results reveal that both B2XY and F-BNBN-H monolayers exhibit spatially separated conduction band minimum (CBM) and valence band maximum (VBM), as well as vacuum level differences at the opposite surfaces due to the intrinsic dipole. The F-BNBN-H monolayer has excellent redox ability for water splitting, because its CBM is located at the surface with a lower vacuum level and its VBM is distributed on the opposite surface possessing a higher vacuum level. By sharp contrast, B2XY monolayers have limited or vanishing redox ability, because their CBM is located at the surface with a higher vacuum level and their VBM is distributed on the opposite surface with a lower vacuum level. This work emphasizes the negative role of vacuum level differences of photocatalysts caused by the intrinsic dipole in water splitting.

Genetic diversity and phylogenetic analysis of Chinese Han and Li ethnic populations from Hainan Island by 30 autosomal insertion/deletion polymorphisms.

With the characteristics of low mutation rate, length variation and short amplicon size, insertion/deletion polymorphisms (InDels) have the advantages of both short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs). Herein, people of two ethnicities from Hainan Island were genotyped for the first time using the Investigator DIPplex kit. We investigated the forensic parameters of the 30 InDels and the phylogenetic relationships among different populations. The accumulated powers of discrimination and powers of exclusion were 0.999 999 999 9646 and 0.9897 in the Hainan Han population and 0.999 999 999 9292 and 0.9861 in the Hainan Li population, respectively. Additionally, population comparisons among geographically, ethnically and linguistically diverse populations via cluster heatmap, multidimensional scaling, principal component analysis, phylogenetic tree and STRUCTURE analyses demonstrated that the Hainan Han population had genetic similarities to the other Han, She and Tujia populations, while the Hainan Li population had close genetic relationships to the Zhuang and Miao groups; both populations had a high degree of genetic differentiation from most Turkic-speaking populations. Aforementioned results suggested that the 30 autosomal InDels are highly polymorphic and informative, which are suitable for human identification and population genetics.

Screening and selection of 21 novel microhaplotype markers for ancestry inference in ten Chinese subpopulations.

Genetic findings suggested ethnolinguistically diverse populations in China harbor differentiated genetic structure and complex evolutionary admixture histories, providing the genetic basis and theoretical foundation for forensic biogeographical ancestry inference (BGAI). Forensic assays for BGAI among intracontinental eastern Eurasians were previously conducted mainly based on SNPs or InDels. Microhaplotypes, as a set of closely linked SNPs within 200 base pairs, possess the advantages of both STRs and SNPs and have great potential in forensic ancestry inference. However, the forensic assay developed based on ancestry-informative microhaplotypes in the BGAI remains to be further explored, especially in China, which has rich genetic diversity. We described a new BGAI panel based on 21 novel identified ancestry-informative microhaplotypes that focused on dissected finer-scale ancestry compositions of Chinese populations. We initially screened all possible microhaplotypes with high Fst values among five East Asian populations and finally employed 21 candidate microhaplotypes in two multiplex SNaPshot assays. Forensic amplification efficiency and statistically/physically phased haplotypes of the 21 microhaplotypes were validated using SNaPshot and massively parallel sequencing (MPS) platforms. Next, we validated the efficiency of these microhaplotypes for BGAI in 764 individuals from ten Chinese populations using SNaPshot technology. The fine-scale ancestry source and ancestry proportion estimated by principal component analysis (PCA), multidimensional scaling (MDS), phylogenetic tree and model-based STRUCTURE among worldwide populations and East Asians showed that our customized panel could provide a higher discrimination resolution in both continental population stratification and East Asian regional substructure. East Asian populations could be classified into linguistically/geographically different intracontinental subpopulations (Tibeto-Burman, Tai-Kadai and others). Finally, we obtained a higher estimated accuracy using training and tested datasets in the microhaplotype-based panel than traditional SNP-based panels. Generally, the above results demonstrated that this microhaplotype panel was robust and suitable for forensic BGAI in Chinese populations, which provided high discriminatory power for continental populations and discriminated East Asians into linguistically restricted subpopulations.

Microwave ablation vs. cryoablation for treatment of primary and metastatic pulmonary malignant tumors.

At present, minimally invasive surgery is one of the primary strategies for the treatment of malignant pulmonary tumors. Although, there are some comparative studies between microwave ablation and radiofrequency for the treatment of malignant pulmonary tumors, there are few studies that have investigated the comparison between microwave ablation and cryoablation. The aim of the study was to retrospectively compare the efficacy and complications of microwave ablation (MWA) and cryoablation in the treatment of malignant pulmonary tumors. A retrospective analysis was performed on 48 patients with malignant lung tumors treated with MWA or cryoablation in The Third Hospital of Mianyang and The Affiliated Hospital of North Sichuan Medical College between June 2014 and June 2018. Of these patients, 29 received MWA and 19 received cryoablation. Intraprocedural pain was evaluated by using the visual analog scale (VAS). The intraprocedural pain, response rates, overall survival (OS) and complications rates were compared between the MWA group and cryoablation group. The results showed that the patients in the MWA group experienced more pain than those in cryoablation group as the MWA group VAS scores were much higher than those in cryoablation group (P<0.001). The overall response rate of the MWA group [21/29 (72.41%)] was not significantly different from the cryoablation group [14/19 (73.68%)] (P=0.92). The 6-, 12-, 24- and 36-month OS rates in the MWA group and cryoablation group were 92.72, 81.28, 64.54 and 54.91%, and 94.07, 81.13, 57.33 and 43.04%, respectively. No significant differences were found in the OS rate between the two groups (P=0.79). The complication rates in the MWA and cryoablation groups were 34.48 and 36.84%, respectively; there was no significant difference between the two groups (P=0.59). No patients died during the perioperative period. Cryoablation had a similar therapeutic effect compared with MWA in the treatment of pulmonary malignant tumors, but was associated with less pain.

The genomic history of southwestern Chinese populations demonstrated massive population migration and admixture among proto-Hmong-Mien speakers and incoming migrants.

Southwest China was the crossroad for the initial settler people of East Asia, which shows the highest diversity in languages and genetics. This region played a significant role in the formation of the genetic makeup of the proto-Hmong-Mien-speaking people and in the north-to-south human expansion during the Neolithic-to-historic transformation. Their genetic history covering migration events and the admixture processes still needs to be further explored. Therefore, in the current study, we have generated genome-wide data from three genomic aspects covering autosomal, mitochondrial and Y-chromosomal regions in 260 Hmong-Mien, Tibeto-Burman, and Sinitic people from 29 different southwestern Chinese groups, and further analyzed them with 2676 published modern and ancient Eurasian genomes. Here, we have noticed a new southwestern East Asian genetic cline composed of the Hmong-Mien-specific ancestry enriched in modern Hmong and Pathen. This newly identified southern inland East Asian lineage contributed to a great extent of the gene pool in the modern southern East Asians. We also have observed genetic substructure among Hmong-Mien-speaking populations. The southern Hmong-Mien-speaking people showed more genetic affinity with modern Tai-Kadai/Austroasiatic people, while the northern Hmong-Mien speakers expressed a closer genetic connection with the Neolithic-to-modern northern East Asians. Moreover, southwestern Sinitic populations had a strong genomic affinity with the adjacent Hmong-Mien-speaking populations and the lowlander Tibeto-Burman-speaking populations, which suggested the large-scale genetic admixture occurred between them. Allele-sharing-based qpAdm/qpGraph results further confirmed that all included southwestern Chinese populations could be modeled as a mixed result of the major ancestry component from the northern millet farmers in the Yellow River basin and the minor ancestry component from the southern rice farmers in the Yangtze River basin. Usually, this newly identified Hmong-Mien-associated southern East Asian ancestry could improve our understanding of the full-scale genetic landscape of the evolutionary and admixture history of southwestern East Asians. Further ancient genomic studies from southeastern China are required to shed deeper light on our established phylogeny context.

Forensic nanopore sequencing of microhaplotype markers using QitanTech's QNome.

In recent years, extraordinary progress has been made in genome sequencing technologies, which has led to a decrease in cost and an increase in the diversity of sequenced genomes. Nanopore sequencing is one of the latest genome sequencing technologies. It aims to sequence longer contiguous pieces of DNA, which are essential for resolving structurally complex regions, and provides a new approach for forensic genetics to detect longer markers in real time. To date, multiple studies have been conducted to sequence forensic markers using MinION from Oxford Nanopore Technologies (ONT), and the results indicate that nanopore sequencing holds promise for forensic applications. Qitan Technology (QitanTech) recently launched its first commercial nanopore genome sequencer, QNome. It could achieve a read length of more than 150 kbp, and could generate approximately 500 Mb of data in 8 h. In this pilot study, we explored and validated this alternative nanopore sequencing device for microhaplotype (MH) profiling using a custom set of 15 MH loci. Seventy single-contributor samples were divided into 7 batches, each of which included 10 samples and control DNA 9947A and was sequenced by QNome. MH genotypes generated from QNome were compared to those from Ion Torrent sequencing (Ion S5XL system) to evaluate the accuracy and stability. Twelve samples randomly selected from the last three batches and Control DNA 9947A were also subjected to ONT MinION sequencing (with R9.4 flow cell) for parallel comparison. Based on MHtyper, a bioinformatics workflow developed for automated MH designation, all MH loci can be genotyped and reliably phased using the QNome data, with an overall accuracy of 99.83% (4 errors among 2310 genotypes). Three occurred near or in the region of homopolymer sequences, and one existed within 50 bp of the start of the sequencing reaction. In the last 15 samples (12 individual samples and 3 replicates of control DNA 9947A), two SNPs located at 4-mer homopolymers failed to obtain reliable genotypes on the MinION data. This study shows the potential of state-of-the-art nanopore sequencing methods to analyze forensic MH markers. Given the rapid pace of change, sporadic and nonrepetitive errors presented in this study are expected to be resolved by further developments of nanopore technologies and analysis tools.