Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

OBJECTIVES: This systematic review examines recent pharmacoeconomic literature on denosumab' cost-effectiveness for bone metastasis treatment, providing evidence-based insights to guide healthcare policy decisions. METHODS: A comprehensive literature search was performed across Cochrane, PubMed, EMBASE (Ovid), CNKI, and Wanfang databases to identify original articles published between 2017 and 2023. Key words consisted of bone metastases, denosumab, and cost-effectiveness in the search strategy. The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022). Data was extracted regarding methodological characteristics and cost-effectiveness analyses. RESULTS: A total of 111 studies were retrieved, of which 6 met the inclusion criteria. All included studies were based on clinical trials and published literature data and exhibited high methodological quality. Up to 83% (5 out of 6) of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid. The adjusted incremental cost-effectiveness ratios varied substantially by tumor type, ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained. CONCLUSIONS The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid. The application of CHEER (2022) enhances the reliability of pharmacoeconomic evaluations.
Denosumab/therapeutic use* ; Humans ; Bone Neoplasms/economics* ; Cost-Benefit Analysis

OBJECTIVE: To evaluate the protective effects of resveratrol against acute lung injury (ALI) and investigate the potential mechanisms underlying the reactive oxygen species (ROS)-triggered thioredoxin-interacting protein (TXNIP)/NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) pathway. METHODS: C57BL/6 mice and J774A.1 cells were selected as the research subjects. Thirty Mice were randomly divided into 5 groups of 6 in each group: control with 0.9% saline, 5 mg/kg lipopolysaccharide (LPS) 24 h, 25 mg/kg resveratrol + 5 mg/kg LPS, 100 mg/kg resveratrol + 5 mg/kg LPS, and 4 mg/kg NLRP3 inhibitor CY-09 + 5 mg/kg LPS. For cell stimulation, cells were pretreated with 5 and 20 µmol/L resveratrol for 2 h, and stimulated with or without 1 µg/mL LPS and 3 mmol/L ATP for 2 h. The antioxidant N-acetyl-L-cysteine (NAC, 2 µmol/L) was used as the positive control group. Hematoxylin and eosin staining was used to evaluate the degree of lung LPS-induced tissue damage, and enzyme-linked immunosorbent assay was used to evaluate the contents of interleukin-1 β (IL-1 β) and IL-18 in the serum and cell supernatant. ROS and malondialdehyde (MDA) levels in the lung tissue were detected using the corresponding kits. Western blotting was used to detect the expressions of TXNIP, high-mobility group box 1 (HMGB1), NLRP3, as well as cysteine-aspartic acid protease 1 (caspase-1) and gasdermin D (GSDMD) along with their cleaved forms in lung tissue. Additionally, reverse transcription quantitative polymerase chain reaction was performed to analyze the expression of related inflammatory cytokines. ROS content was detected using flow cytometry and confocal laser microscopy. Mitochondrial morphological changes were observed using transmission electron microscopy, and HMGB1 expression was detected using immunofluorescence. RESULTS: Resveratrol significantly alleviated LPS-induced lung damage with reduced inflammation, interstitial edema, and leukocyte infiltration (P<0.01). It also decreased serum levels of IL-1 β and IL-18 (P<0.05), while downregulating the expressions of NLRP3, IL-6, and other inflammatory markers at both the protein and mRNA levels (P<0.05). Notably, the higher dose (100 mg/kg) demonstrated a better effect than the lower dose (25 mg/kg). In macrophages, resveratrol reduced IL-1 β and IL-18 following LPS and ATP stimulation, suppressed HMGB1 translocation, and inhibited formation and activation of the NLRP3 inflammasome (P<0.05 or P<0.01). These anti-inflammatory effects were mediated through the suppression ROS accumulation (P<0.01) and mitochondrial dysfunction. Transmission electron microscopy revealed that resveratrol preserved mitochondrial structure, preventing the mitochondrial damage seen in LPS-treated groups (P<0.01). The expressions of cleaved caspase-1, cleaved GSDMD, and cytoplasmic HMGB1 were all reduced following resveratrol treatment (P<0.01). Moreover, resveratrol inhibited dissociation of TXNIP from thioredoxin, blocking subsequent activation of NLRP3 and downstream inflammatory cytokines (P<0.01). Similarly, the higher concentration of resveratrol (20 µ mol/L) exhibited superior efficacy in vitro. CONCLUSION Resveratrol can reduce the inflammatory response following ALI and inhibit the activation of NLRP3 inflammasome and the level of HMGB1 in the cytoplasm by inhibiting ROS overproduction.
Acute Lung Injury/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Resveratrol/pharmacology* ; Reactive Oxygen Species/metabolism* ; Inflammation/complications* ; Mice, Inbred C57BL ; Carrier Proteins/metabolism* ; Signal Transduction/drug effects* ; Lipopolysaccharides ; Thioredoxins/metabolism* ; Mice ; Lung/drug effects* ; Male ; Cell Line ; Interleukin-1beta/metabolism* ; Cell Cycle Proteins ; Stilbenes/therapeutic use*

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

[Objective] To analyze the influence of the cycle length of hepatitis B surface antigen (HBsAg) double reagent positive samples collected from voluntary blood donors in Guangzhou on the detection results. [Methods] A total of 127 044 blood samples from voluntary blood donors at Guangzhou Blood Center from August 10 to December 9, 2023 were selected. Two ELISA reagents were used for HBsAg detection, and samples with HBsAg double reagent positive and S/CO values<10 were tested continuously for 7 days to observe the changes in their S/CO values. [Results] A total of 505 HBsAg double reagent positive samples were detected, of which 52 had S/CO values less than 10. After 7 consecutive days of uninterrupted testing, the S/CO values of Wantai (median 5 decreased to 3) and Xinchuang (median 5 decreased to 3) showed an overall downward trend, and the HBsAg missed detection rate showed an upward trend (from 0 on the first day to 1/10 000 on the seventh day). A total of 13 cases had negative double reagent test results within the 7-day testing cycle. [Conclusion] With the extension of the detection cycle, the S/CO value of HBsAg detection shows a downward trend, and the missed detection rate of HBsAg shows an upward trend. Samples used for HBsAg detection should be tested promptly after sampling to improve the quality of blood testing.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.