Decitabine-based treatment strategy improved the outcome of HSCT in JMML: a retrospective cohort study.

Introduction: Pre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients. Methods: This retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival. Results: There were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002). Conclusion: Implementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments.

Temporal dynamics changes in the vaginal fluid microbiome: Implications for body fluid identification and estimating time since deposition (TsD) for forensics.

Vaginal fluid analysis plays a crucial role in sexual assault investigations. However, vaginal fluid found at crime scenes is usually subject to a certain duration of exposure. This study thus aimed to assess the influence of different durations of exposure to indoor environment on the vaginal microbiota. The 16S rDNA high-throughput sequencing was used on vaginal fluid samples exposed for short-term (30 days) and long-term (240 days), respectively. Despite potential contamination from environmental microorganisms, particularly following long-term exposure, the results indicated that the vaginal microbiota after exposure was still dominated by Lactobacillus. Both in short-term and long-term exposure involving vaginal fluid, there were clusters with time-dependent characteristics, wherein the relative abundances of associated microbial genera showed a trend of increasing or decreasing over time. In addition, each bodily fluid presented with a unique array of dominant bacterial genera, enabling the differentiation of exposed vaginal fluid samples from other bodily fluids (semen, skin, saliva, feces) with a remarkable 98.75 % accuracy rate. Furthermore, the mean absolute error achieved by the long-term deposition time prediction model was 13.54 days. The mean absolute error for the short-term deposition time prediction model was notably lower, reaching just 2.05 days. In summary, this study investigates the variations in microbial communities within vaginal fluid subjected to different indoor exposure durations and explores their potential in body fluid identification and estimating the time since deposition, thereby contributing valuable supporting evidence in forensic investigations.

Combined analysis of the microbiome and metabolome to reveal the characteristics of saliva from different diets: a comparison among vegans, seafood-based omnivores, and red meat (beef and lamb) omnivores.

Introduction: Revealing individual characteristics is supportive for identifying individuals in forensic crime. As saliva is one of the most common biological samples used in crime scenes, it is important to make full use of the rich individual information contained in saliva. The aim of this study was to explore the application of the microbiome in forensic science by analysing differences in the salivary microbiome and metabolome of healthy individuals with different dietary habits. Methods: We performed 16S rDNA sequencing analysis based on oral saliva samples collected from 12 vegetarians, 12 seafood omnivores and 12 beef and lamb omnivores. Non-targeted metabolomics analyses were also performed based on saliva samples from healthy individuals. Results: The results showed that the dominant flora of vegetarians was dominated by Neisseria (belonging to the phylum Proteobacteria), while seafood omnivores and beef and lamb omnivores were dominated by Streptococcus (belonging to the phylum Firmicutes). NDMS-based and cluster analyses showed that vegetarian dieters were significantly differentiated from meat dieters (seafood omnivores and beef and lamb omnivores), which may be related to the fact that high-fiber diets can create a different salivary flora structure. Variants were also detected in salivary metabolic pathways, including positive correlations with Lipid metabolism, Amino acid metabolism, Carbohydrate metabolism, and Nucleotide metabolism in vegetarians, and correlations in seafood omnivores. In order to select salivary microorganisms and metabolic markers that can distinguish different dietary profiles, a random forest classifier model was constructed in this study, and the results showed that individuals with different dietary profiles could be successfully distinguished based on the core genera and metabolites such as Streptococcus, Histidinyl-Valine. Conclusion: Our study provides a supportive basis for the application of salivary polyomics in order to reveal the dietary characteristics of individuals for forensic investigation and crime solving.

Changes in the microbial community of semen exposed to different simulated forensic situations.

Semen is one of the common body fluids in sexual crime cases. The current methods of semen identification have certain limitations, so it is necessary to search for other methods. In addition, there are few reports of microbiome changes in body fluids under simulated crime scenes. It is essential to further reveal the changes in semen microbiomes after exposure to various simulated crime scenes. Semen samples from eight volunteers were exposed in closed plastic bags, soil, indoor, cotton, polyester, and wool fabrics. A total of 68 samples (before and after exposure) were collected, detected by 16S rDNA sequencing, and analyzed for the microbiome signature. Finally, a random forest model was constructed for body fluid identification. After exposure, the relative abundance of Pseudomonas and Rhodococcus changed dramatically in almost all groups. In addition, the treatment with the closed plastic bags or soil groups had a greater impact on the semen microbiome. According to the Shannon indices, the alpha diversity of the closed plastic bags and soil groups was much lower than that of the other groups. Attention should be given to the above two scenes in practical work of forensic medicine. In this study, the accuracy of semen recognition was 100%. The exposed semen can still be correctly identified as semen based on its microbiota characteristics. In summary, semen microbiomes exposed to simulated crime scenes still have good application potential for body fluid identification. IMPORTANCE: In this study, the microbiome changes of semen exposed to different environments were observed, and the exposed semen microbiome still has a good application potential in body fluid identification.

Skin locations inference and body fluid identification from skin microbial patterns for forensic applications.

Given that microbiological analysis can be an alternative method that overcomes the shortcomings of traditional forensic technology, and skin samples may be the most common source of cases, the analysis of skin microbiome was investigated in this study. High-throughput sequencing targeting the V3-V4 region of 16S rRNA gene was performed to reveal the skin microbiome of healthy individuals in Guangdong Han. The bacterial diversity of the palm, navel, groin and plantar of the same individual was analyzed. The overall classification based on 16S rRNA gene amplicons revealed that the microbial composition of skin samples from different anatomical parts was different, and the dominant bacterial genus of the navel, plantar, groin and palm skin were dominated by Cutibacterium, Staphylococcus, Corynebacterium and Staphylococcus, respectively. PCoA analysis showed that the skin at these four anatomical locations could only be grouped into three clusters. A predictive model based on random forest algorithm showed the potential to accurately distinguish these four anatomical locations, which indicated that specific bacteria with low abundance were the key taxa. In addition, the skin microbiome in this study is significantly different from the dominant microbiome in saliva and vaginal secretions identified in our previous study, and can be distinguished from these two tissue fluids. In conclusion, the present findings on the community and microbial structure details of the human skin may reveal its potential application value in assessing the location of skin samples and the type of body fluids in forensic medicine.

Interventricular septum involvement is related to right ventricular dysfunction in anterior STEMI patients without right ventricular infarction: a cardiovascular magnetic resonance study.

The value of cardiovascular magnetic resonance (CMR) in assessing and predicting acute right ventricular (RV) dysfunction in patients with anterior ST-segment elevation myocardial infarction (STEMI) remains ascertained. Eighty eight patients with anterior STEMI were prospectively recruited and underwent CMR examinations within one week following the coronary intervention. Patients with RV ejection fraction (RVEF) less than 2 standard deviations below the average at the center (RVEF ≤ 45.0%) were defined as having RV dysfunction. The size of infarction, segmental wall motion, and T1 and T2 mapping values of global myocardium and the interventricular septum (IVS) were measured. Predictive performance was calculated using receiver-operating characteristic curve analysis and logistic regression test. Twenty two patients presented with RV dysfunction. The RV dysfunction group had a larger IVS infarct extent (54.28 ± 10.35 vs 33.95 ± 15.09%, P < 0.001) and lower left ventricle stroke volume index (33.93 ± 7.96 vs 42.46 ± 8.14 ml/m2, P < 0.001) compared to the non-RV dysfunction group. IVS infarct extent at 48.8% best predicted the presence of RV dysfunction with an area under the curve of 0.864. Left ventricular stroke volume index (LVSVI) and IVS infarct extent were selected by stepwise multivariable logistic regression analysis. Lower LVSVI (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.79 to 0.99; P = 0.044) and higher IVS infarct extent (OR 1.16; 95% CI 1.05 to 1.33; P = 0.01) were found to be independent predictors for RV dysfunction. In patients with anterior STEMI, those with larger IVS infarct extent and worse LV function are more likely to be associated with RV dysfunction.

Analysis of research topics and trends in investigator-initiated research/trials (IIRs/IITs): A topic modeling study.

BACKGROUND: With the exponential growth of publications in the field of investigator-initiated research/trials (IIRs/IITs), it has become necessary to employ text mining and bibliometric analysis as tools for gaining deeper insights into this area of study. By using these methods, researchers can effectively identify and analyze research topics within the field. METHODS: This study retrieved relevant publications from the Web of Science Core Collection and conducted bioinformatics analysis. The latent Dirichlet allocation model, which is based on machine learning, was utilized to identify subfield research topics. RESULTS: A total of 4315 articles related to IIRs/IITs were obtained from the Web of Science Core Collection. After excluding duplicates and articles with missing abstracts, a final dataset of 3333 articles was included for bibliometric analysis. The number of publications showed a steady increase over time, particularly since 2000. The United States, Germany, the United Kingdom, the Netherlands, Canada, Denmark, Japan, Switzerland, and France emerged as the most productive countries in terms of IIRs/IITs. The citation analysis revealed intriguing trends, with certain highly cited articles showing a significant increase in citation frequency in recent years. A model with 45 topics was deemed the best fit for characterizing the extensively researched fields within IIRs/IITs. Our analysis revealed 10 top topics that have garnered significant attention, spanning domains such as community health, cancer treatment, brain development and disease mechanisms, nursing research, and stem cell therapy. These top topics offer researchers valuable directions for further investigation and innovation. Additionally, we identified 12 hot topics, which represent the most cutting-edge and highly regarded research areas within the field. CONCLUSION: This study contributes to a comprehensive understanding of the current research landscape and provides valuable insights for researchers working in this domain.

Correlation between surrogate endpoints and overall survival in unresectable hepatocellular carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

This study aimed to assess the therapeutic effect of immune checkpoint inhibitors (ICIs) in patients with unresectable hepatocellular carcinoma (uHCC) and investigate the correlation between surrogate endpoints and overall survival (OS). A systematic literature search included phase I, II, and III clinical trials comparing ICIs to placebo or other therapies for uHCC treatment. Correlations between OS and surrogate endpoints were evaluated using meta-regression analyses and calculating the surrogate threshold effect (STE). The correlation analysis showed a weak association between OS and progression-free survival (PFS), with an R2 value of 0.352 (95% CI: 0.000-0.967). However, complete response (CR) exhibited a strong correlation with OS (R2 = 0.905, 95% CI: 0.728-1.000). Subgroup analyses revealed high correlations between OS and PFS, CR, stable disease (SD), and DC in phase III trials (R2: 0.827-0.922). For the ICI + IA group, significant correlations were observed between OS and SD, progressive disease (PD), and grade 3-5 immune-related adverse events (irAEs) (R2: 0.713-0.969). Analyses of the correlation between survival benefit and risk of mortality across various time points showed a strong association within the first year (R2: 0.724-0.868) but a weak association beyond one year (R2: 0.406-0.499). In ICI trials for uHCC, PFS has limited utility as a surrogate endpoint for OS, while CR exhibits a strong correlation with OS. Subgroup analyses highlight high correlations between OS and PFS, SD, and DC in phase III trials. Notably, the ICI + IA group shows significant associations between OS and SD, PD, and grade 3-5 irAEs. These findings offer valuable insights for interpreting trial outcomes and selecting appropriate endpoints in future clinical studies involving ICIs for uHCC patients.

Response of salivary microbiome to temporal, environmental, and surface characteristics under in vitro exposure.

The microbiome of saliva stains deposited at crime scenes and in everyday settings is valuable for forensic investigations and environmental ecology. However, the dynamics and applications of microbial communities in these saliva stains have not been fully explored. In this study, we analyzed saliva samples that were exposed to indoor conditions for up to 1 year and to different carriers (cotton, sterile absorbent cotton swab, woolen, dacron) in both indoor and outdoor environments for 1 month using high-throughput sequencing. The analysis of microbial composition and Mfuzz clustering showed that the salivary flora, specifically Streptococcus (cluster7), which was associated with microbial contamination, remained stable over short periods of time. However, prolonged exposure led to significant differences due to the invasion of environmental bacteria such as Pseudomonas and Achromobacter. The growth and colonization of environmental flora were promoted by humidity. The neutral model predictions indicated that the assembly of salivary microbial communities in outdoor environments was significantly influenced by stochastic processes, with environmental characteristics having a greater impact on community change compared to surface characteristics. By incorporating data from previous studies on fecal and vaginal secretion microbiology, we developed RF and XGBoost classification models that achieved high accuracy (>98 %) and AUC (>0.8). Additionally, a RF regression model was created to determine the time since deposition (TsD) of the stains. Time inference models yielded a mean absolute error (MAE) of 7.1 days for stains exposed for 1 year and 14.2 h for stains exposed for 14 days. These findings enhance our understanding of the changes in the microbiome of saliva stains over time, in different environments, and on different surfaces. They also have potential applications in assessing potential microbial contamination, identifying body fluids, and inferring the time of deposition.

Integrative group psychotherapy for patients with somatic symptom disorder: A randomized controlled trial.

The study aimed to determine whether specific integrative group psychotherapy (IGPT), based on CBT, combined with techniques of psychodynamic therapy and mindful body and emotional awareness is more effective than non-specific supportive group psychotherapy (SGPT) and treatment as usual (TAU) alone. A total of 120 SSD patients were randomly assigned to IGPT, SGPT or TAU groups. Both IGPT and SGPT showed significantly lower SSD-12 scores at the 4, 8, and 12-week follow-ups compared to TAU. No significant differences were observed between IGPT and SGPT at any follow-up point. These findings highlight the potential benefits of group psychotherapy in SSD treatment.

A novel approach for exploring the regional features of vaginal fluids based on microbial relative abundance and alpha diversity.

Vaginal fluids are one of the most common biological samples in forensic sexual assault cases, and their characterization is vital to narrow the scope of investigation. Presently, approaches for identifying vaginal fluids in different regions are not only rare but also have certain limitations. However, the microbiome has shown the potential to identify the source of body fluids and reveal the characteristics of individuals. In this study, 16S rRNA gene high-throughput sequencing was used to characterize the vaginal microbial community from three regions, Sichuan, Hainan and Hunan. In addition, data on relative abundance and alpha diversity were used to construct a random forest model. The results revealed that the dominant genera in the three regions were Lactobacillus, followed by Gardnerella. In addition, Ureaplasma, Nitrospira, Nocardiodes, Veillonella and g-norank-f-Vicinamibacteraceae were significantly enriched genera in Sichuan, llumatobacter was enriched in Hainan, and Pseudomonas was enriched in Hunan. The random forest classifier based on combined data on relative abundance and alpha diversity had a good ability to distinguish vaginal fluids with similar dominant microbial compositions in the three regions. The study suggests that combining high-throughput sequencing data with machine learning models has good potential for application in the biogeographic inference of vaginal fluids.

Developmental validation of a novel multiple genotyping assay with 24 Canine STR loci.

Canine individual identification and parentage testing are essential in various fields, including forensics and breeding programs. This study aimed to develop and validate the Canine 25 A kit, a multiplex polymerase chain reaction (PCR) system designed to address these critical requirements. This novel system enables the simultaneous amplification of 24 canine autosomal short tandem repeat (STR) loci and one sex-determining marker. Validation of the Canine 25 A kit was conducted following the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines, demonstrating significant sensitivity, high inhibitor tolerance, canine specificity within a mixture, species specificity, and precision in genotype determination. The Canine 25 A kit was crucial in resolving several forensic cases, such as casework samples from a dog attack incident and parentage determination. Its effectiveness in genotyping these samples highlights its significance in forensic applications. Population genetic parameter analysis revealed a high discriminatory power, as indicated by the calculated combined discrimination power (CDP) values for each breed exceeding 0.999 999 999 999, while the combined power of exclusion (CPE) surpassed 0.9999. Overall, the Canine 25 A kit offers a precise and dependable tool for canine individual identification and parentage determination.

Changes in the microbial community after vaginal fluid exposure in different simulated forensic situations.

If vaginal fluid is found on clothing or on the body of the suspect, it may indicate the occurrence of sexual assault. Therefore, it is important to collect the victim's vaginal fluid at different sites from the suspect. Previous studies have revealed that fresh vaginal fluids can be identified based on 16S rRNA gene sequencing data. However, the influence of environmental factors on the stability of microbial markers must be investigated before being used in forensic practice. We collected vaginal fluid from nine unrelated individuals and placed each individual of vaginal swab on five different substrates. A total of 54 vaginal swabs were analyzed using 16S rRNA on the V3-V4 regions. Then, we constructed a random forest model including the samples of all vaginal fluids in this study and the other four types of body fluids in our previous studies. The alpha diversity of vaginal samples increased after exposure to the substrate environment for 30 days. The dominant vaginal bacteria were Lactobacillus and Gardnerella, which remained relatively stable after exposure, with Lactobacillus being the most abundant in all substrates, while Gardnerella was more abundant in other substrates than in the polyester fiber substrate. Except for bed sheets, Bifidobacterium significantly declined when placed on other substrates. Rhodococcus and Delftia from the substrate environment migrated to the vaginal samples. Rhodococcus was abundant in polyester fibers, and Delftia was abundant in wool substrates, while those environmental bacteria were all in low abundance in bed sheets. Overall, the bed sheet substrates showed a good retention capacity for the dominant flora and could reduce the number of taxa migrated by the environment compared with the other substrates. Both fresh and exposed vaginal samples of the same individuals could mostly be clustered and clearly distinguished from different individuals, showing the potential of individual identification, and the confusion matrix value of body fluid identification for vaginal samples was 1. In summary, vaginal samples placed on the surface of different substrates retained their stability and demonstrated good application potential for individual and body fluid identification.

Development and application of a multiplex PCR system for forensic salivary identification.

In forensics, accurate identification of the origin of body fluids is essential for reconstructing a crime scene or presenting strong evidence in court. Microorganisms have demonstrated great potential in body fluid identification. We developed a multiplex PCR system for forensic salivary identification, which contains five types of bacteria:Streptococcus salivarius, Neisseria subflava, Streptococcus. mutans, Bacteroides thetaiotaomicron, and Bacteroides. uniformis. And the validated studies were carried out following the validation guidelines for DNA analysis methods developed by the Scientific Working Group on DNA Analysis Methods (SWGDAM), which included tests for sensitivity, species specificity, repeatability, stability, and mixed samples, trace samples, case samples, and a population study. Our result depicted that the lowest detection limit of the system was 0.01 ng template DNA. Moreover, the corresponding bacteria can still be detected when the amount of saliva input is low to 0.1 µL for DNA extraction. In addition, the target bacteria were not detected in the DNA of human, seven common animals, and seven bacteria DNA and in nine other body fluid samples (skin, semen, blood, menstrual blood, nasal mucus, sweat, tears, urine, and vaginal secretions). Six common inhibitors such as indigo, EDTA, hemoglobin, calcium ions, alcohol and humic acid were well tolerated by the system. What is more, the salivary identification system recognized the saliva component in all mixed samples and simulated case samples. Among 400 unrelated individuals from the Chinese Han population analyzed by this novel system, the detection rates of N. subflava, S. salivarius, and S. mutans were 97.75%, 70.75%, and 19.75%, respectively, with 100% identification of saliva. In conclusion, the salivary identification system has good sensitivity, specificity, stability, and accuracy, which can be a new effective tool for saliva identification.

Recent progress in patent foramen ovale and related neurological diseases: A narrative review.

Patent foramen ovale (PFO) is a common congenital cardiac abnormality when the opening of the interatrial septum is not closed in adulthood. This abnormality affects 25% of the general population. With the development of precision medicine, an increasing number of clinical studies have reported that PFO is closely related to various neurological diseases such as stroke, migraine, obstructive sleep apnea, and decompression syndrome. It has also been suggested that PFO closure could be effective for preventing and treating these neurological diseases. Therefore, increasing attention has been given to the prevention, diagnosis, and treatment of PFO-related neurological diseases. By reviewing existing literature, this article focuses on the pathogenesis, epidemiology, and clinical characteristics of PFO-related neurological diseases, as well as the prevention and treatment of different neurological diseases to discuss, and aims to provide current progress for this field and decision-making evidence for clinical practice.

Core outcomes were rarely reported overall in systematic reviews on acupuncture for osteoarthritis: a cross-sectional meta-epidemiological study.

OBJECTIVE: To identify a comprehensive list of outcomes and explore the reporting rate of core outcome sets (COS) and related factors in systematic reviews (SRs) of acupuncture for osteoarthritis (OA). STUDY DESIGN AND SETTING: Databases were searched for the relative SRs. Descriptive statistics were calculated as frequencies and percentages. Binary logistic regression was used to explore the factors affecting the reporting rate of COS. RESULTS: We included 59 SRs. Outcome measures reported in the SRs were classified into 11 domains and 67 unique outcomes. No SR completely reported COS. In COS released in 2016, 75% of outcomes (6/8) were only reported by ⩽5% SRs. In COS released in 2019, the reporting rate was very low (from 0% to 17%) for 73.3% of outcomes (11/15). SRs published in the most recent 5 years had a significantly greater possibility of reporting COS (odds ratio (OR) = 4.74, 95% confidence interval (CI) = 1.33 to 16.88, p = 0.016). CONCLUSION: Core outcomes were rarely reported in systematic reviews of acupuncture for OA, with considerable heterogeneity in the use of outcomes. The publication of COS in the COMET (Core Outcome Measures in Effectiveness Trials) database may help promote the reporting of COS. We encourage systematic reviewers to use relevant COS.

Fecal microbial signatures of healthy Han individuals from three bio-geographical zones in Guangdong.

Important forensic evidence traced from crime scenes, such as fecal materials, can help in the forensic investigation of criminal cases. Intestines are the largest microbial pool in the human body whose microbial community is considered to be the human "second fingerprint". The present study explored the potential for community characteristics of gut microbes in forensic medicine. Fecal microbiota profiles of healthy individuals from three representative Han populations (Guangzhou, Shantou and Meizhou) in Guangdong Province, China were evaluated using High-throughput sequencing of V3-V4 hypervariable regions of the 16SrRNA gene. Results of the present study showed that at the genus level, Shantou, Guangzhou, and Meizhou behaved as Enterotype1, Enterotype2, and Enterotype3, which were mainly composed of Bacteroides, Prevotella, and Blautia, respectively. Based on OTU abundance at the genus level, using the random forest prediction model, it was found that there might be potential for distinguishing individuals of Guangzhou, Meizhou, and Shantou according to their fecal microbial community. Moreover, the findings of the microbial community of fecal samples in the present study were significantly different from that of saliva samples reported in our previous study, and thus it is evident that the saliva and feces can be distinguished. In conclusion, this study reported the fecal microbial signature of three Han populations, which may provide basic data for the potential application in forensic practice, containing body fluid identification, and geographical inference.

The Molecular Associations of Signet-Ring Cell Carcinoma in Colorectum: Meta-Analysis and System Review.

Background: Signet ring cell carcinoma (SC) accounts for 1% of total colorectal cancer (CRC) cases and is associated with aggressive behaviors, such as lymphatic invasion and distant metastases, resulting in poor prognosis. To date, there is still a lack of consensus on the genetic etiology underpinning this cancer subtype. This study aimed to clarify the molecular associations of SC by using meta-analysis and a systematic review. Methods: PubMed, Embase, and Cochrane Library were searched for studies evaluating the KRAS, BRAF, P53 statuses, and microsatellite instability (MSI) in CRC patients with different histological subtypes, including SC. The diagnosis of SC is defined as the signet ring cells comprising ≥50 percent of the tumor mass. By dividing the studies into subgroups based on the composition of control groups, such as classic adenocarcinoma (AC; no SC components) and non-SC (including those with SC components < 50%), the relative risk (RR) of molecular alterations for SC in each study were pooled using a random-effects model. Two reviewers identified trials for inclusion, assessed quality, and extracted data independently. Results: Data from 29 studies consisting of 9366 patients were included in this analysis. SC was associated positively with MSI (RR 1.78, 95% CI 1.34 to 2.37; 95% CI 0.77 to 4.15; p = 0.0005), BRAF mutation (RR 1.99, 95% CI 1.21 to 3.26; 95%CI 0.68 to 5.82; p = 0.0146), and negatively with KRAS mutation (RR 0.48, 95% CI 0.29 to 0.78; 95% CI 0.09 to 2.49; p = 0.0062). No association was found between SC and P53 expression (RR 0.92, 95% CI 0.76 to 1.13; 95%CI 0.61 to 1.39; p = 0.3790). Moreover, it was associated negatively with P53 gene mutations (RR 0.92, 95% CI 0.77 to 1.09; 95% CI 0.46 to 1.82; p = 0.1568), and P53 protein (RR 0.93, 95% CI 0.58 to 1.49; 95% CI 0.40 to 2.17; p = 0.6885). Conclusions: The molecular etiology of SC may be associated with the BRAF and MSI pathways. Its features, such as the high frequency of BRAF mutation, could partly explain its less favorable outcomes and limited effects of traditional chemotherapy.

Herbal Granules of Heat-Clearing and Detoxifying for Children with Mild Hand, Foot, and Mouth Disease: A Bayesian Network Meta-Analysis.

Background: Regarding ethical considerations of randomized controlled trials (RCTs) in children, limited evidence for mild hand, foot, and mouth disease (HFMD) is available. Recently, with the increasing but result-conflicting RCTs published around herbal granules of heat-clearing and detoxifying (HGs-HD), a head-to-head comparison is urgently needed to choose a suitable therapy for clinical practice. Materials and Methods: This study was conducted according to the preferred reporting items for systematic review and meta-analysis (PRISMA) extension statement for network meta-analysis (NMA). Eight databases (Medline, Embase, and so on) and two trial registry platforms (https://www.clinicaltrials.gov and https://www.chictr.org.cn) were searched from inception to May 26, 2021. The NMA was performed using a random-effect model. The treatment hierarchy was summarized and reported as the surface under the cumulative ranking curve (SUCRA) probability values. The rankings of each HGs-HD at primary outcomes were estimated by the inverse probability weighting (IPW) approach and averaged, which presents the comprehensive improvement effect. Results: Forty-five RCTs involving 18 interventions were included that studied 5,652 children with mild HFMD. The best performance probability for improving symptoms were respectively presented in terms of fever (Xiao'er Resuqing granules, XRGs, 94.9%), rash (Xiao'er Jinqiao granules, 83.9%), hospitalization (Xiao'er Chiqiao Qingre granules, XCQGs, 92.7%), vesicles (Jinlianhua granules, 91.0%), appetite (Xiao'er Chiqiao Qingre granules, XCQGs, 86.7%), and ulcers (Kouyanqing granules, KouGs, 88.8%). Furthermore, the top 5 rankings for comprehensive improvement effect were Yanning granules (YNGs, 2.256), XCQGs (2.858), XRGs (3.270), KouGs (7.223), and Houerhuan Xiaoyan granules (HXGs, 7.597). Conclusions: This is the first NMA of HGs-HD head-to-head comparisons for children with mild HFMD. Of those, YNGs, XCQGs, XRGs, KouGs, and HXGs could be recommended as potential choices for clinical practice. Of course, the results should be interpreted with caution due to the limited high-quality RCTs.

Integrating the salivary microbiome in the forensic toolkit by 16S rRNA gene: potential application in body fluid identification and biogeographic inference.

Saliva is a common body fluid with significant forensic value used to investigate criminal cases such as murder and assault. In the past, saliva identification often relied on the α-amylase test; however, this method has low specificity and is prone to false positives. Accordingly, forensic researchers have been working to find new specific molecular markers to refine the current saliva identification approach. At present, research on immunological methods, mRNA, microRNA, circRNA, and DNA methylation is still in the exploratory stage, and the application of these markers still has various limitations. It has been established that salivary microorganisms exhibit good specificity and stability. In this study, 16S rDNA sequencing technology was used to sequence the V3-V4 hypervariable regions in saliva samples from five regions to reveal the role of regional location on the heterogeneity in microbial profile information in saliva. Although the relative abundance of salivary flora was affected to a certain extent by geographical factors, the salivary flora of each sample was still dominated by Streptococcus, Neisseria, and Rothia. In addition, the microbial community in the saliva samples in this study was significantly different from that in the vaginal secretions, semen, and skin samples reported in our previous studies. Accordingly, saliva can be distinguished from the other three body fluids and tissues. Moreover, we established a prediction model based on the random forest algorithm that could distinguish saliva between different regions at the genus level even though the model has a certain probability of misjudgment which needs more in-depth research. Overall, the microbial community information in saliva stains might have prospects for potential application in body fluid identification and biogeographic inference.