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This study utilized metabolomics and metagenomics to investigate the microbial composition and functions in low- and high-salt Chinese horse bean-chili pastes (CHCPs). The results showed that 25 key metabolites were identified to distinguish the flavor attributes between the two samples. Leuconostoc was identified as the dominant microbiota in low-salt CHCP, while Pantoea prevailed in the high-salt CHCP. Compared to traditional high-salt fermentation, low-salt and inoculated fermentation promoted the increase in the relative abundances of Companionlactobacillus, Levilactobacillus, Tetragenococcus, Zygosaccharomyces and Wickerhamiella as well as the enrichment of carbohydrate and amino acid metabolic pathways, which contributed to the enhancement of characteristic flavor compounds. Further metabolic pathway reconstruction elucidated 21 potential microbial genera associated with the formation of key metabolites, such as Leuconostoc, Levilactobacillus, Pantoea, and Pectobacterium. This study may provide insights for optimizing the fermentation process and improving the flavor quality of low-salt CHCP and similar fermentation products. KEYWORDS: Low-salt fermentation Hight-salt fermentation Chinese horse-bean chili paste Flavor formation Metabolomics Metagenomics.

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Cerebral hemorrhage represents a severe neurological disorder with significant implications for patient health. Numerous factors play a crucial role in determining the prognosis of this condition. In recent years, research has highlighted the polymorphism of the apolipoprotein E (APOE) gene as being closely associated with cerebrovascular diseases and the recovery of neurological functions. This study aims to explore the influence of APOE gene polymorphism on cerebral oxygen saturation, cerebral electrical activity, and the clinical prognosis of patients experiencing cerebral hemorrhage. The goal is to identify potential new biomarkers that could enhance the management and treatment of individuals who have suffered from this type of bleed in the brain.To investigate this relationship, the study analyzed the ε2, ε3, and ε4 alleles of the APOE gene through gene sequencing techniques. Measurements of cerebral oxygen saturation and electrical brain activity were conducted using specialized equipment including brain oxygen monitors and electroencephalography (EEG) devices. Additionally, detailed clinical data were gathered, encompassing neurological function assessments and the duration of recovery for each patient.A comparative analysis was performed to assess the cerebral oxygen saturation levels, EEG characteristics, and overall prognosis associated with the different APOE genotypes. The findings indicated that patients carrying the APOE ε4 allele exhibited significantly impaired cerebral oxygen metabolism and diminished electrical activity in the initial stages of intracerebral hemorrhage. This impairment potentially results in a worse prognostic outlook when compared to individuals who are non-carriers of the APOE ε4 allele. Furthermore, the relationship between the pulsatility index (PR) and regional cerebral oxygen saturation (rScO2) was found to be negatively correlated. Specifically, patients with intracerebral hemorrhage who exhibited elevated PR levels alongside reduced rScO2 demonstrated poorer clinical outcomes.

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Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror spatial patterns of progenitor streams surrounding interneuron nests, as seen during human brain development. Integrating these findings with genome-wide CRISPR-Cas9 screens identifies genes upregulated in interneuron lineage progenitors as major dependencies. Among these, CDK6 emerges as a targetable vulnerability: DHG-H3G34 tumor cells show enhanced sensitivity to CDK4/6 inhibitors and a CDK6-specific degrader, promoting a shift toward more mature interneuron-like states, reducing tumor growth, and prolonging xenograft survival. Notably, a patient with progressive DHG-H3G34 treated with a CDK4/6 inhibitor achieved 17 months of stable disease. This study underscores interneuronal progenitor-like states, organized in characteristic niches, as a distinct vulnerability in DHG-H3G34, highlighting CDK6 as a promising clinically actionable target.

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Seminal plasma extracellular vesicles (SPEVs) play an important role in regulating sperm motility by delivering various cargoes, such as miRNAs, mRNAs, proteins and metabolites. However, information on the lipid compositions of SPEVs and their roles in semen quality is limited. Here, we performed high-throughput transcriptomic and lipidomic analysis on SPEVs isolated from 20 boars with high or low sperm motility. Then, we evaluated the lipid composition and gene expression characteristics of SPEVs and identified the specific lipids and genes related to sperm motility. As a result, a total of 26 lipid classes were identified in SPEVs, and five subclasses, CerG2, CerG3, LPE, LPS and TG, were significantly different in boars with high and low sperm motility. In addition, 195 important lipids and 334 important genes were identified by weighted gene coexpression analysis (WGCNA) and differential expression analysis. We observed that several important genes and lipids in SPEVs potentially influence sperm motility via glycerophospholipid metabolism, glycerolipid metabolism, the sphingolipid signaling pathway and the ferroptosis pathway. Furthermore, we found a significant correlation between the content of 22 lipids and the expression levels of 67 genes (|cor| > 0.8, P < 0.05). Moreover, we observed that three important gene-lipid linkages (CerG1 (d22:0/24:0) - RCAN3, Cer (d18:1/24:0) - SCFD2 and CerG1 (d18:0/24:1) - SCFD2) were strongly correlated with sperm motility. Based on the results, some genes and lipids in SPEVs may play important roles in sperm motility by interacting with sperm through important pathways.

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A comprehensive understanding of the evolution of soybean climate potential productivity and its response to climate change in Heilongjiang Province can offer reference and basis for further tapping soybean production potential and realizing stable and high yield of soybean in the frigid region. Based on meteorological data from 80 meteorological stations in Heilongjiang Province from 1961 to 2020, we estimated photosynthesis, light temperature, and climate potential productivity of soybean by the stepwise correction method, examined the spatiotemporal variations by spatial interpolation and statistical analysis methods, and analyzed the impact of changes in climate factors such as radiation, temperature, and precipitation on climate potential productivity. The results showed that during the study period, the average values of photosynthesis potential productivity (YQ), light-temperature potential productivity (YT), and climate potential productivity (YW) of soybean in Heilongjiang Province were 7533, 6444, and 3515 kg·hm-2, respectively. The temporal changes of those variables showed significant increasing trends, with increases of 125.9, 182.9, and 116.1 kg·hm-2·(10 a)-1, respectively. For the spatial distribution, YQ, YT, YW were characterized by high values in plains and lower in the mountains, and gradually decreased from southwest to northeast. Compared with that during 1961-1990, the high value zone of YW in period 1991-2020 expanded by 7.1%, and the low value zone decreased by 5.1%. YW showed a significant response to climate change. The potential temperature growth period was extended due to climate warming. The continuous increase in thermal resources, combined with relatively sufficient precipitation, effectively alleviated the negative impact of the decline in light resources on soybean production in Heilongjiang Province. The projected "warm and humid" climate would comprehensively boost climate potential productivity of soybean in Heilongjiang Province.

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Whether the dynamic development of peripheral inflammation aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis (IVT), remains unclear and warrants further study. In this study, total of 1034 patients with acute ischemic stroke who underwent IVT were enrolled. Serum leukocyte variation (whether increase from baseline to 24 h after IVT), National Institutes of Health Stroke Scale (NIHSS), infarct volume, early neurologic deterioration (END), the unfavorable outcome at 3-month (modified Rankin Scale [mRS] score ≥3) and mortality were recorded. Serum brain injury biomarkers, including Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100ß, neuron-specific enolase (NSE), were measured to reflect the extent of brain injury. We found that patients with increased serum leukocytes had elevated brain injury biomarkers (GFAP, UCH-L1, and S100ß), larger infarct volume, higher 24 h NIHSS, higher proportion of END, unfavorable outcome and mortality. Furthermore, an increase in serum leukocytes was independently associated with infarct volume, 24 h NIHSS, END, and unfavorable outcome at 3 months, and serum UCH-L1, S100ß, and NSE levels. These results suggest that an increase in serum leukocytes indicates severe brain injury and may be used to predict the outcome of patients with ischemic stroke who undergo IVT.

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Trichomes are specialized epidermal outgrowths covering the aerial parts of most terrestrial plants. There is a large species variability in occurrence of different types of trichomes such that the molecular regulatory mechanism underlying the formation and the biological function of trichomes in most plant species remain unexplored. Here, we used Chrysanthemum morifolium as a model plant to explore the regulatory network in trichome formation and terpenoid synthesis and unravel the physical and chemical roles of trichomes in constitutive defense against herbivore feeding. By analyzing the trichome-related genes from transcriptome database of the trichomes-removed leaves and intact leaves, we identified CmMYC2 to positively regulate both development of T-shaped and glandular trichomes as well as the content of terpenoids stored in glandular trichomes. Furthermore, we found that the role of CmMYC2 in trichome formation and terpene synthesis was mediated by interaction with CmMYBML1. Our results reveal a sophisticated molecular mechanism wherein the CmMYC2-CmMYBML1 feedback inhibition loop regulates the formation of trichomes (non-glandular and glandular) and terpene biosynthesis, collectively contributing to the enhanced resistance to Spodoptera litura larvae feeding. Our findings provide new insights into the novel regulatory network by which the plant synchronously regulates trichome density for the physical and chemical defense against herbivory.

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OBJECTIVE: Radiation therapy is applied in the treatment of head and neck cancer patients. However, oral-health-related side effects like hyposalivation and a higher prevalence of caries have been shown. This study aims to assess the influence of different radiotherapy doses on the mechanical properties, roughness, superficial microstructure, and crystallinity of the enamel and dentin of human premolar teeth. METHODS: Specimens (n = 25) were categorized into five groups based on the radiation dose received (0, 10, 30, 50, and 70 Gy). The enamel and dentin of these specimens were subjected to a microhardness tester, profilometer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and X­ray diffraction (XRD) before and after different irradiation doses and compared to hydroxylapatite in each group. The data were analyzed using repeated-measures analysis of variance (ANOVA). RESULTS: Therapeutic radiation doses of 30, 50, and 70 Gy led to a decrease in the microhardness and an increase in the average roughness of the enamel, and rougher surfaces were observed in the mixed three-dimensional images. Moreover, in the dentin, a similar outcome could be observed for more than 10 Gy. The main crystalline phase structure remained hydroxylapatite, but the crystallinity decreased and the crystalline size increased above 10 Gy. The superficial micromorphology revealed granulation, fissures, and cracks in a dose-dependent manner. Radiation below 70 Gy had little effect on the hydroxylapatite concentration during the whole experiment. CONCLUSION: Above a radiation dose of 30 Gy, the micromorphology of the tooth enamel changed. This occurred for dentin above 10 Gy, which indicates that dentin is more sensitive to radiotherapy than enamel. The radiation dose had an effect on the micromorphology of the hard tissues of the teeth. These results illustrate the possible mechanism of radiation-related caries and have guiding significance for clinical radiotherapy.

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Glycyl radical enzymes (GREs) catalyze mechanistically diverse radical-mediated reactions, playing important roles in the metabolism of anaerobic bacteria. The model bacterium Escherichia coli MG1655 contains two GREs of unknown function, YbiW and PflD, which are widespread among human intestinal bacteria. Here, we report that YbiW and PflD catalyze ring-opening C-O cleavage of 1,5-anhydroglucitol-6-phosphate (AG6P) and 1,5-anhydromannitol-6-phosphate (AM6P), respectively. The product of both enzymes, 1-deoxy-fructose-6-phosphate (DF6P), is then cleaved by the aldolases FsaA or FsaB to form glyceraldehyde-3-phosphate (G3P) and hydroxyacetone (HA), which are then reduced by the NADH-dependent dehydrogenase GldA to form 1,2-propanediol (1,2-PDO). Crystal structures of YbiW and PflD in complex with their substrates provided insights into the mechanism of radical-mediated C-O cleavage. This "anhydroglycolysis" pathway enables anaerobic growth of E. coli on 1,5-anhydroglucitol (AG) and 1,5-anhydromannitol (AM), and we probe the feasibility of harnessing this pathway for the production of 1,2-PDO, a highly demanded chiral chemical feedstock, from inexpensive starch. Discovery of the anhydroglycolysis pathway expands the known catalytic repertoire of GREs, clarifies the hitherto unknown physiological functions of the well-studied enzymes FsaA, FsaB, and GldA, and demonstrates how enzyme discovery efforts can cast light on prevalent yet overlooked metabolites in the microbiome.

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Cutaneous melanoma is a highly lethal form of cancer. Developing a medical image segmentation model capable of accurately delineating melanoma lesions with high robustness and generalization presents a formidable challenge. This study draws inspiration from cellular functional characteristics and natural selection, proposing a novel medical segmentation model named the vital characteristics cellular neural network. This model incorporates vital characteristics observed in multicellular organisms, including memory, adaptation, apoptosis, and division. Memory module enables the network to rapidly adapt to input data during the early stages of training, accelerating model convergence. Adaptation module allows neurons to select the appropriate activation function based on varying environmental conditions. Apoptosis module reduces the risk of overfitting by pruning neurons with low activation values. Division module enhances the network's learning capacity by duplicating neurons with high activation values. Experimental evaluations demonstrate the efficacy of this model in enhancing the performance of neural networks for medical image segmentation. The proposed method achieves outstanding results across numerous publicly available datasets, indicating its potential to contribute significantly to the field of medical image analysis and facilitating accurate and efficient segmentation of medical imagery. The proposed method achieves outstanding results across numerous publicly available datasets, with an F1 score of 0.901, Intersection over Union of 0.841, and Dice coefficient of 0.913, indicating its potential to contribute significantly to the field of medical image analysis and facilitating accurate and efficient segmentation of medical imagery.

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Background: Programmed cell death protein 1 (PD-1) inhibitor therapy has become a routine treatment for advanced non-small cell lung cancer (NSCLC). However, only some NSCLC patients would benefit from anti-PD-1 therapy. We urgently need to identify biomarkers associated with clinical response to change treatment strategies promptly for patients who fail to benefit from anti-PD-1 treatment. This study was aimed to explore whether circulating CD4+ T cells and CD8+ T cells could be biomarkers for predicting anti-PD-1 efficacy. Methods: In this study, 118 NSCLC patients who received anti-PD-1 therapy were enrolled. The percentages of circulating CD4+ T cells and CD8+ T cells before and after anti-PD-1 treatment were determined by flow cytometry. The programmed cell death ligand 1 (PD-L1) expression of tumor tissues was detected by immunocytochemistry. The anti-PD-1 treatment efficacy was assessed by immune response evaluation criteria in solid tumors (iRECIST). Results: The percentage of CD4+ T cells and CD4+/CD8+ ratio in the peripheral blood (PB) was significantly elevated after anti-PD-1 treatment. In contrast, the percentage of CD8+ T cells in the PB was significantly decreased after anti-PD-1 treatment. Furthermore, we found that the percentages of CD4+ T cells and CD4+/CD8+ ratios considerably increased, and the percentages of CD8+ T cells significantly reduced in the effective group. On the contrary, the patients in the ineffective group showed no significant differences in the biomarkers. Multivariate logistic revealed that the percentage of CD4+ T cells at baseline was an independent predictor of anti-PD-1 treatment. The area under the curve (AUC) of the CD4+ T cells percentage was 0.7834 with a cut-off value of 28.53% (sensitivity =82.5%, specificity =66.23%). Conclusions: The percentage of CD4+ T cells at baseline could predict anti-PD-1 efficacy in NSCLC patients.

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Fresh yak meat is highly nutritious and prone to spoilage, so developing suitable preservation methods is crucial. In this study, hydrogel coatings composed of konjac glucomannan, Lactiplantibacillus plantarum and gallic acid (KGX) were applied to preserve fresh yak meat under ice temperature (-1 °C). After 16 days, KGX group showed lowest total viable count (5.3 ± 0.1 log cfu/g) and total volatile basic nitrogen (13.02 ± 1.40 mg/100 g), which did not exceed the relevant standards of fresh meat. Combined assessments of color, texture, pH, drip loss rate, and thiobarbituric acid reactive substances indicated that KGX coating effectively prolonged yak meat preservation. High-throughput sequencing revealed that KGX coating effectively reduced the abundance of Pseudomonas and Candida. The application of L. plantarum hydrogel coatings in conjunction with ice temperature increased the shelf life of fresh yak meat to 16-20 days, suggesting its potential as a viable preservation method for fresh meat.

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Background: Upper limb motor impairment is a common consequence of stroke, and the effectiveness and underlying mechanisms of rehabilitation therapy for improving upper limb function remain uncertain. Functional near-infrared spectroscopy, a reliable wearable neuroimaging technique, holds promise for investigating brain activity during functional tasks. This study aims to explore the synchronous oxygenation characteristics of the central cortex and upper-limb flexors during a grasping task and investigate the rehabilitation mechanisms of upper limb motor function in individuals with stroke. Methods: Participants with stroke who demonstrate the ability to grasp and lift cubic wood blocks of different sizes (2.5cm3, 5cm3, and 10cm3) using their affected hand will be divided into three groups: A, B, and C. Each group will consist of twenty stroke patients, resulting in a total of sixty participants with stroke. Additionally, twenty matched healthy subjects will be enrolled as a control group. Comprehensive assessments will be conducted before and after the intervention, including blood oxygen parameter monitoring of the cerebral cortex and upper limb flexors using fNIRS during the grasping task. Other assessments will include MyotonPRO, the Modified Ashworth Scale, the upper extremity section of the Fugl-Meyer Assessment, the Action Research Arm Test, and the Modified Barthel Index. The study will be undertaken between January 2024 and September 2025. Conclusions: The results of this trial will provide an in-depth understanding of the Characteristics of central cortex and upper-limb flexors synchronous oxygenation during grasping task and how it may relate to the rehabilitation mechanism of upper limb motor function in people with stroke. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2400080619.

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Objective: To investigate whether using Zishen Yutai Pills (ZYP) following embryo transfer would affect the live birth rate in frozen-thawed embryo transfer (FET) cycles. Methods: A retrospective analysis was performed on 15044 FET cycles in the Reproductive Medicine Center of The Affiliated Chenggong Hospital of Xiamen University from January 2013 to December 2020. Patients who used Zishen Yutai Pills were defined as Zishen Yutai Pills Group (ZYP, n=2735), while patients who did not use them were defined as Non- Zishen Yutai Pills Group (Non-ZYP, n=12309). The propensity score matching method was used to control for potential confounders between the two groups, and logistic regression analysis was also used to assess whether using ZYP would affect the live birth rate. Results: After propensity score matching, basic characteristics were similar between the two groups. Using ZYP did not increase the pregnancy rate (51.5% vs. 52.7%, P=0.372), and live birth rate (43.0% vs. 44.7%, P=0.354). This was also confirmed by the logistic regression analysis results (OR=0.95, 95%CI=0.85-1.06). In the subgroup analysis of the endometrial preparation protocols, however, it was found that the use of ZYP in patients with natural cycles increased the live birth rate (47.4% vs. 41.5%, P=0.004). A significant interaction between endometrial preparation and ZYP was found (OR=1.38, 95%CI=1.07-1.79) in the multivariate model. Conclusion: The use of ZYP may not improve the live birth rate of unselected patients in FET cycles. However, a future study is needed on the effect of ZYP in natural cycles for endometrial preparation.

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Background: Pythium insidiosum (P. insidiosum) is the causative agent of pythiosis, an infectious disease with a high morbidity and fatality rate. Pythiosis cases have increased dramatically during the past ten years, particularly in tropical and subtropical areas. Sadly, microbiologists and medical professionals know very little about pythiosis, and the disease is frequently challenging to identify. It is frequently misdiagnosed as a fungal infection. Methods: We report two cases of pythiosis, one was Pythium keratitis, the other was cutaneous pythiosis. The patient with corneal infection had no underlying disease, while the patient with cutaneous pythiosis had a history of liver cirrhosis, diabetes, and psoriasis. The corneal sample and subcutaneous pus were sent for metagenomic Next-Generation Sequencing (mNGS). To further diagnose the isolated strain, P. insidiosum zoospores were induced to produce by co-incubation with sterile grass leaves in sterile pond water. Their zoospores were used as an inoculum for drug susceptibility testing by disk diffusion and broth microdilution method. Results: The mNGS of two cases were reported as P. insidiosum. Zoospores were produced after incubation 48h. The zoospores were collected for drug susceptibility assay. All antifungal drugs, antibacterial drugs of ß-Lactams, vancomycin, levofloxacin, ciprofloxacin, gentamicin, trimethoprim-sulfamethoxazole, clindamycin have no inhibitory activity against P. insidiosum in vitro. Minocycline, tigecycline, linezolid, erythromycin and azithromycin have significant in vitro activity against P. insidiosum. Based on the susceptibility results, the drug was changed from itraconazole to linezolid and minocycline, along with multiple debridements and drainage for cutaneous pythiosis. The patient was discharged after 24 days of treatment. Conclusions: Early and accurate identification, combined with aggressive surgical debridement and appropriate drug therapy, can greatly improve patient managements. Conventional culture and zoospore induction remain gold standard for diagnosis; however, DNA-based method should be performed simultaneously. The drug susceptibility testing provides profound effects on proper drug selection against P. insidiosum.

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CONTEXT: Dietary factors are crucial in the onset and development of autoimmune thyroid disease (AITD), but the relationship between specific fatty acids and AITD remains unexplored. METHODS: We analyzed the US National Health and Nutrition Examination Survey (NHANES) 2007-2012 data on 3949 men and 3964 women aged 20 years and over with valid data on TPOAb, TgAb and details of fat intake, using multivariable regression models to examine the relationship of fat intake and specific fatty acid intake with thyroid autoimmunity. RESULTS: Of the 7913 participants, 7.5% had TgAb seropositivity and 11.9% had TPOAb seropositivity. The seropositivity of TgAb and TPOAb was more common in low-fat intake participants. In the overall population and men, fats were associated with thyroid autoimmunity before and after full adjustment for age, ethnicity, body mass index, smoking status and urine iodine concentration (total fat: OR=0.64, 95% CI 0.49 to 0.83; SFA: OR=0.65, 95% CI 0.51 to 0.84; MUFA: OR=0.65, 95% CI 0.50 to 0.85; PUFA: OR=0.76, 95% CI 0.57 to 0.995, after full adjustment in men). Some specific fatty acids followed a similar pattern. The association between fats and TgAb seropositivity was significant in the overall population and men. The association between fats and TPOAb seropositivity was only found in the overall population. CONCLUSION: We found a strong association between fat consumption and thyroid autoimmunity in the overall population and men from the nationally representative population-based survey. Fat and fatty acid consumption may be of benefit to individuals with thyroid autoimmunity.

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OBJECTIVES: To explore early diagnostic biological markers for Leigh syndrome caused by the m.8993T>G mutation. METHODS: A retrospective analysis was performed on the clinical data of four children diagnosed with m.8993T>G mutation-related mitochondrial disease at the Children's Hospital of Chongqing Medical University from January 2014 to January 2024. Additionally, a literature review was conducted. RESULTS: All four children had plasma amino acid and acylcarnitine analyses that revealed decreased citrulline levels, and one child was initially identified through neonatal genetic metabolic disease screening. According to the literature review, there were 26 children with mitochondrial disease and hypocitrullinemia caused by the m.8993T>G mutation (including the four children in this study). Among these, 12 children exhibited clinical phenotypes of Leigh syndrome or Leigh-like syndrome, while 18 children were identified with hypocitrullinemia and/or elevated levels of 3-hydroxyisovalerylcarnitine (C5-OH) during neonatal genetic metabolic disease screening. CONCLUSIONS: Hypocitrullinemia may serve as a potential biomarker for the early diagnosis of m.8993T>G mutation-associated Leigh syndrome, detectable as early as during neonatal genetic metabolic disease screening.

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BACKGROUND: In China, the problem of HIV infection among the older people has become increasingly prominent. This study aimed to analyze the pattern and influencing factors of HIV transmission based on a genomic and spatial epidemiological analysis among this population. METHODS: A total of 432 older people who were aged ≥ 50 years, newly diagnosed with HIV-1 between January 2018 and December 2021 and without a history of ART were enrolled. HIV-1 pol gene sequence was obtained by viral RNA extraction and nested PCR. The molecular transmission network was constructed using HIV-TRACE and the spatial distribution analyses were performed in ArcGIS. The multivariate logistic regression analysis was performed to analyze the factors associated with clustering. RESULTS: A total of 382 sequences were successfully sequenced, of which CRF07_BC (52.3%), CRF01_AE (32.5%), and CRF08_BC (6.8%) were the main HIV-1 strains. A total of 176 sequences entered the molecular network, with a clustering rate of 46.1%. Impressively, the clustering rate among older people infected through commercial heterosexual contact was as high as 61.7% and three female sex workers (FSWs) were observed in the network. The individuals who were aged ≥ 60 years and transmitted the virus by commercial heterosexual contact had a higher clustering rate, while those who were retirees or engaged other occupations and with higher education degree were less likely to cluster. There was a positive spatial correlation of clustering rate (Global Moran I = 0.206, P < 0.001) at the town level and the highly aggregated regions were mainly distributed in rural area. We determined three large clusters which mainly spread in the intra-region of certain towns in rural areas. Notably, 54.5% of cases in large clusters were transmitted through commercial heterosexual contact. CONCLUSIONS: Our joint analysis of molecular and spatial epidemiology effectively revealed the spatial aggregation of HIV transmission and highlighted that towns of high aggregation were mainly located in rural area. Also, we found vital role of commercial heterosexual contact in HIV transmission among older people. Therefore, health resources should be directed towards highly aggregated rural areas and prevention strategy should take critical persons as entry points.

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Background: Multiple sclerosis (MS) is the most common non-traumatic disabling disease affecting young adults. A definitive curative treatment is currently unavailable. Many randomized controlled trials (RCTs) have reported the efficacy of Chinese herbal medicine (CHM) on MS. Because of the uncertain quality of these RCTs, the recommendations for routine use of CHM for MS remain inconclusive. The comprehensive evaluation of the quality of RCTs of CHM for MS is urgent. Methods: Nine databases, namely, PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Sinomed, Wanfang Database, China National Knowledge Infrastructure, and VIP Database, were searched from inception to September 2023. RCTs comparing CHM with placebo or pharmacological interventions for MS were considered eligible. The Consolidated Standards of Reporting Trials (CONSORT) and its extension for CHM formulas (CONSORT-CHM Formulas) checklists were used to evaluate the reporting quality of RCTs. The risk of bias was assessed using the Cochrane Risk of Bias tool. The selection criteria of high-frequency herbs for MS were those with cumulative frequency over 50% among the top-ranked herbs. Results: A total of 25 RCTs were included. In the included RCTs, 33% of the CONSORT items and 21% of the CONSORT-CHM Formulas items were reported. Eligibility title, sample size calculation, allocation concealment, randomized implementation, and blinded description in CONSORT core items were reported by less than 5% of trials. For the CONSORT-CHM Formulas, the source and authentication method of each CHM ingredient was particularly poorly reported. Most studies classified the risk of bias as "unclear" due to insufficient information. The top five most frequently used herbs were, in order, Radix Rehmanniae Preparata, Radix Rehmanniae Recens, Herba Epimedii, Scorpio, and Poria. No serious adverse effect had been reported. Conclusions: The low reporting of CONSORT items and the unclear risk of bias indicate the inadequate quality of RCTs in terms of reporting completeness and result validity. The CONSORT-CHM Formulas appropriately consider the unique characteristics of CHM, including principles, formulas, and Chinese medicinal substances. To improve the quality of RCTs on CHM for MS, researchers should adhere more closely to CONSORT-CHM Formulas guidelines and ensure comprehensive disclosure of all study design elements.

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