ObjectiveIn the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by the internal transcribed spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms. MethodsITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using Linear Discriminant Analysis Effect Size (LEfSe) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples. ResultsAmong the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted. ConclusionSignificant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.

The aim of this study was to investigate the improvement effect of Wenpi Pills(WPP) on non-alcoholic fatty liver disease(NAFLD). The experiment was divided into two parts, using C57BL/6 mouse models induced by a high-fat diet(HFD) and a methionine and choline deficiency diet(MCD). The HFD-induced experiment lasted for 16 weeks, while the MCD-induced experiment lasted for 6 weeks. Mice in both parts were divided into four groups: control group, model group, low-dose WPP group(3.875 g·kg~(-1), WPP＿L), and high-dose WPP group(15.5 g·kg~(-1), WPP＿H). After sample collection from the HFD-induced mice, lipid content in the serum and liver, liver function indexes in the serum, and hepatic pathology were examined. Real-time fluorescent quantitative reverse transcription PCR(qRT-PCR) was used to detect the expression of lipid-related genes. After sample collection from the MCD-induced mice, serum liver function indexes and inflammatory factors were measured, and hepatic pathology and lipid changes were analyzed by hematoxylin-eosin(HE) staining and widely targeted lipidomic profiling, respectively. The results from the HFD-induced experiment showed that, compared with the HFD group, WPP administration significantly reduced the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol(TC) in the serum, with the WPP＿H group showing the most significant improvement. HE staining results indicated that, compared with the HFD group, WPP treatment improved the morphology of white adipocytes, reducing their size, and alleviated hepatic steatosis and lipid droplet accumulation. The qRT-PCR results suggested that WPP might increase the mRNA expression of liver cholesterol-converting genes, such as liver X receptor α(LXRα) and cytochrome P450 family 27 subfamily A member 1(CYP27A1), as well as lipid consumption genes like peroxisome proliferator-activated receptor α(PPARα) and adenosine mono-phosphate-activated protein kinase(AMPK). Meanwhile, WPP decreased the mRNA expression of lipid synthesis genes, including fatty acid synthetase(FAS), stearoyl-CoA desaturase 1(SCD1), and sterol regulatory element-binding protein 1c(SREBP-1c), thereby reducing liver lipid accumulation. The results from the MCD-induced experiment showed that, compared with the MCD group, WPP administration reduced the levels of ALT, AST, and inflammatory factors in the serum, thereby alleviating liver injury and the inflammatory response. HE staining of liver tissue indicated that WPP effectively improved hepatic steatosis. Non-targeted lipidomics analysis showed that WPP improved lipid metabolism disorders in the liver, mainly by affecting the metabolism of TG and cholesterol esters. In conclusion, WPP can improve hepatic lipid accumulation in NAFLD mice induced by both HFD and MCD. This beneficial effect is primarily achieved by alleviating liver injury and inflammation, as well as regulating lipid metabolism.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Lipid Metabolism/drug effects* ; Mice ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Diet, High-Fat/adverse effects* ; Liver/drug effects* ; Humans ; Disease Models, Animal ; Methionine

Proanthocyanidin B_2(PAC-B_2), a polyphenolic dimeric compound comprising two epicatechin molecules linked by a C-C bond, is extensively found in traditional Chinese medicines, with anti-tumor and anti-oxidant activities. Given the limited bioavailability, a thorough investigation and comprehensive understanding of PAC-B_2 metabolism in vivo are essential for elucidating therapeutic forms and mechanisms. In the present study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) in the negative ion mode was employed to acquire the MS/MS information of PAC-B_2 and metabolites in urine and feces samples of the rats administrated with PAC-B_2. Online energy-resolved MS(ER-MS) was applied as supplementary to obtain the full collision energy ramp-MS~2 spectra(FCER-MS~2) of isomers-of-interest, which implied comprehensive MS~2 information of targeted compounds. Finally, the possible metabolic pathways of PAC-B_2 in rats were proposed. The primary fragmentation behaviors of PAC-B_2 in the negative ion mode included quinone methide fission between C_4-C_8 bond, retro Diels-Alder cracking of F-ring, heterocyclic ring fission of C-ring, and neutral loss of small molecules such as H_2O. A total of 25 metabolites were tentatively elucidated in urine and feces samples of rats administrated with PAC-B_2 by fragmentation pattern and reported literature. Two groups of isomers, M3/M4/M5 and M9/M11, were confirmatively differentiated based on the relationships between optimal collision energy provided by FCER-MS~2 and bond properties, including bond length and bond dissociation energy. In addition to the ring-opening and methylation, PAC-B_2 could also be metabolized into epicatechin and low molecular weight phenolic acids, which were subsequently subjected to dehydroxylation, ring-opening, methylation, sulfation, and glucuronidation. The structural information provided by online ER-MS and FCER-MS~2 enabled the differentiation of isomers and improved the identification confidence. More importantly, the present study deeply analyzes the in vivo metabolic pathways of PAC-B_2, providing a basis for the research on the pharmacological mechanism of this compound.
Animals ; Proanthocyanidins/urine* ; Rats ; Male ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Feces/chemistry* ; Molecular Structure

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

Objective： To systematically evaluate the clinical efficacy and safety of Tonifying kidney and activating blood therapy for the treatment of diabetic mellitus erectile dysfunction. Methods： China National Knowledge Infrastructure(CNKI), Wanfang Data, VIP, Chinese Biomedical Database(CBM), PubMed, Cochrane Library, Embase and Web of Science were searched from inception until October 20th of 2024，for randomized controlled trials of Tonifying kidney and activating blood therapy for the treatment of diabetic erectile dysfunction. Literature screening, quality evaluation, and data extraction were carried out in accordance with relevant standards. The software of RevMan5.4 was used for the analysis of publication bias. And meta-analysis was conducted to assess the impact of this therapy on IIEF-5, total effective rate, adverse reactions. The evidence levels according to the analysis results were evaluated. Results: Totally 19 RCTs were included, involving 1 612 patients. The result of meta-analysis indicated that Tonifying kidney and activating blood therapy had advantages on the improvement of IIEF-5 scores (MD=3.59，95%CI［2.14，5.03］，P<0.01)，total effective rate (OR=4.30，95%CI［3.29，5.32］，P<0.000 01）. However, there was no statistically significant difference in the incidence of adverse reactions(OR=0.98，95%CI［0.48，2.01］，P=0.96) between the two groups. Conclusions： Tonifying kidney and activating blood therapy can improve the clinical efficacy and IIEF-5 score for the patients with diabetic erectile dysfunction. But considering the limited quantity of included studies, more high-quality studies still be needed to validate the therapeutic effect.
Humans ; Male ; Erectile Dysfunction/therapy* ; Randomized Controlled Trials as Topic ; Kidney ; Medicine, Chinese Traditional ; Diabetes Complications/therapy*

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Objective To investigate the effect of liquid-liquid phase separation(LLPS)of YTH domain family protein 2(YTHDF2)on the sodium arsenite-induced malignant transformation of skin cells,providing a new intervention target for the prevention and control of sodium arsenite-induced carcinogenesis.Methods The HaCaT cell model of malignant transformation was constructed by continuous treatment with 1 μmol/L sodium arsenite for 22 weeks,including cells with normal YTHDF2 LLPS(YTHDF2-wt)and cells with inhibited YTHDF2 LLPS(YTHDF2-mut).Confocal microscopy was employed to observe and characterize the LLPS droplets formed by YTHDF2 during sodium arsenite-induced malignant transformation of skin cells.Cell proliferation,scratch healing,and colony formation assays were performed to detect malignant phenotypes.Western blotting,quantitative reverse transcription PCR,and immunofluorescence experiments were conducted to examine the effects of YTHDF2 LLPS on the mRNA and protein levels of phosphatase and tensin homolog deleted on chromosome ten(PTEN)during sodium arsenite-induced malignant transformation of skin cells.Results After 4 weeks of sodium arsenite treatment,LLPS droplets of YTHDF2 appeared in YTHDF2-wt cells,and the number of droplets gradually increased as the treatment time was prolonged(F=35.252,P<0.001),while no phase-separated droplets were observed in YTHDF2-mut cells.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed enhanced proliferation at the time points of 48 h(t=3.654,P=0.006)and 72 h(t=5.458,P<0.001)after 22 weeks of sodium arsenite treatment.The scratch healing rate of YTHDF2-wt cells was increased at the 8th(t=12.137,P<0.001)and 22th(t=4.484,P=0.011)weeks of sodium arsenite treatment.The number of colonies formed by YTHDF2-wt cells was higher at the 4th(t=3.365,P=0.027),8th(t=5.580,P=0.005),and 22th(t=3.328,P=0.029)weeks of sodium arsenite treatment.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed down-regulated protein(t=-3.119,P=0.036)and mRNA(t=4.051,P=0.015) levels of PTEN after 22 weeks of sodium arsenite treatment.Immunofluorescence results showed that after 4 weeks of sodium arsenite treatment,YTHDF2 LLPS droplets in YTHDF2-wt cells were localized to stress granules,translation-related membrane-less organelles.Conclusions During sodium arsenite-induced malignant transformation of skin cells,YTHDF2 undergoes LLPS and localizes to stress granules,translation-related membrane-less organelles.YTHDF2 LLPS participates in sodium arsenite-induced malignant transformation of skin cells by down-regulating the mRNA level of the key tumor suppressor PTEN.
Arsenites/toxicity* ; Sodium Compounds/toxicity* ; Humans ; Cell Transformation, Neoplastic/drug effects* ; PTEN Phosphohydrolase/metabolism* ; Cell Proliferation ; Skin/cytology* ; RNA-Binding Proteins ; Skin Neoplasms/chemically induced* ; Cell Line