ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

Background Animal farming may affect the structure and diversity of gut microbiota of farm workers, but it needs more studies to provide solid evidence. Objective To analyze the diversity characteristics of gut microbiota in dairy farm workers, dairy cows, and the control population (non-animal contact occupational group), and to assess the impact of dairy farming on the gut microbiota of workers. Methods The 16S rRNA full-length amplicon sequencing technology was used to sequence 60 fecal samples from dairy farm workers, 89 from dairy cows, and 50 from the general population. The gut microbiota structure characteristics, including operational taxonomic units (OTUs), alpha diversity, beta diversity, and the composition of species at the phylum, family, and genus levels were analyzed. The differences in gut microbiota among the three groups of samples were compared to explore the impact of occupational exposure on the gut microbiota structure of dairy farm workers. Results A total of 50478 OTUs were identified in the gut microbiota of farm workers, dairy cows, and the general population, with 23613, 42723, and 16592 OTUs, respectively. The number of shared OTUs between the dairy cows and the general population was 12674 (27.17%), between the general population and the farm workers was 10099 (33.54%), and between the dairy cows and the farm workers was 17690 (36.36%). Compared with the general population, the farm workers and dairy cows showed more shared gut microbiota (P<0.01). The abundance of Firmicutes in the gut of the farm workers was higher than that of the general population (P<0.01), while Actinobacteriota and Proteobacteria were the opposite (P<0.01). The alpha diversity of gut microbiota in the farm workers was different from that of the general population. The ACE index of the farm workers was slightly lower than that of the general population and much lower than that of dairy cows (P<0.05), while their Shannon index was higher than that of the general population but lower than that of dairy cows (P<0.01). The linear discriminant analysis effect size (LefSe) showed that the abundances of Lachnospiraceae and Ruminococcaceae in the gut microbiota of the farm workers were significantly higher than those of the general population, while Streptococcaceae, Lactobacillaceae, Bifidobacteriaceae, Enterobacteriaceae, and Erysipelatoclostridiaceae were lower than those of the general population. Conclusion The dairy farm workers shares a certain proportion of common bacterial communities with dairy cows. Dairy farming operations can affect the structure and diversity of the gut microbiota of workers by increasing the abundances of Lachnospiraceae and Ruminococcaceae, while decreasing the abundances of Streptococcaceae, Lactobacillaceae, Bifidobacteriaceae, Enterobacteriaceae, and Erysipelatoclostridiaceae. The study results provide reference data for further exploring the cross-host transmission of pathogens related to occupational exposure in dairy farming.

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

OBJECTIVES: To study the effect of CDC20 knockdown on proliferation, migration and invasion of cervical cancer cells and its underlying mechanism. METHODS: CDC20 expression in cervical cancer tissues was analyzed using the TCGA database, and the protein expressions of CDC20 and β-Catenin in clinical specimens of cervical cancer and adjacent tissues were detected using immunohistochemistry. A dual target sgRNA2&7 sequence for CDC20 gene was designed for CDC20 gene knockdown in cervical cancer C33A cells using CRISPR/Cas9 technology, and CDC20 mRNA and protein expression levels in the transfected cells were detected using qRT-PCR and Western blotting. The changes in proliferation, cell cycle, apoptosis, migration and invasiveness of the transfected cells were evaluated using colony-forming assay, fluorescence activated cell sorting (FACS) and Transwell assay. In the animal experiment, naïve C33A cells and the cells with CDC20 knockdown were injected subcutaneously into the left and right axillae of nude mice (n=5) to observe tumor growth. The expressions of CDC20 and β-Catenin proteins in transfected cells and the xenograft were analyzed using Western blotting, and their interaction was confirmed by co-immunoprecipitation (CoIP) and immunofluorescence co-localization assays. RESULTS: Cervical cancer tissues expressed significantly higher CDC20 and β‑Catenin levels than the adjacent tissues. C33A cells with CDC20 knockdown showed reduced proliferation, increased apoptosis, and lowered migration and invasion abilities. CDC20 knockdown significantly suppressed the growth of C33A cell xenograft in nude mice, and the tumor-bearing mice did not exhibit obvious body mass changes. CDC20 and β-Catenin levels were both significantly lowered in C33A cells with CDC20 knockdown. Co-immunoprecipitation and co-localization assays confirmed the interaction between CDC20 and β‑Catenin. CONCLUSIONS CDC20 is highly expressed in cervical cancer tissues, and CDC20 knockdown can suppress proliferation, invasion, and metastasis while enhancing apoptosis of C33A cells, which is closely related with the regulation of the Wnt/β-Catenin signaling pathway.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; Cdc20 Proteins/genetics* ; Cell Proliferation ; Animals ; Cell Movement ; Neoplasm Invasiveness ; Apoptosis ; Mice, Nude ; beta Catenin/metabolism* ; CRISPR-Cas Systems ; Mice ; Cell Line, Tumor ; Gene Knockout Techniques ; Neoplasm Metastasis

OBJECTIVE: To investigate the differences in indwelling duration, clinical scenarios, and complications between the modified midline catheter (MMC) and the central venous catheter (CVC) in the treatment of patients in the medical intensive care unit (ICU) and the risk factors for complications based on real-world data. METHODS: A retrospective cohort study was conducted. The adult patients admitted to the medical ICU of the Third Xiangya Hospital of Central South University and had undergone placement of either a MMC or a CVC between January 1, 2023, and July 31, 2024, were consecutively enrolled by querying the hospital's electronic medical record system. Based on the type of catheter inserted, the patients were divided into the MMC group and the CVC group. The two groups were compared regarding the selection of catheters in the context of different underlying diseases, the actual clinical application after catheterization, catheter-related complications, the international normalized ratio (INR) and platelet count (PLT) during puncture and catheterization, the length of ICU stay, total length of hospital stay, catheter indwelling duration, and mortality during hospitalization. Multivariate Logistic regression analysis was employed to identify independent risk factors for catheter removal. RESULTS: Among the 274 patients, 52 received a MMC and 222 received a CVC. The utilization rate of MMC was significantly higher than that of CVC in patients with acute respiratory distress syndrome (ARDS), cardiovascular disease, and cancer [ARDS: 92.3% (48/52) vs. 70.3% (156/222), cardiovascular disease: 84.6% (44/52) vs. 54.5% (121/222), cancer: 30.8% (16/52) vs. 17.1% (38/222), all P < 0.05]. However, the use of MMC was significantly lower than CVC when vasoactive drug infusion was required [57.7% (30/52) vs. 79.7% (177/222), P < 0.05]. A significantly higher proportion of patients in the MMC group had a catheter indwelling time ≥ 12 days as compared with the CVC group [32.7% (17/52) vs. 13.5% (30/222), P < 0.05]. There were no statistically significant differences in other underlying diseases, venous access usage, INR and PLT during puncture and catheterization, length of ICU stay, total length of hospital stay, and in-hospital mortality of patients between the two groups. Regarding catheter-related complications, although the incidence of partial or complete catheter removal in the MMC group was significantly higher than that in the CVC group [36.5% (19/52) vs. 5.4% (12/222), P < 0.05], the incidence of puncture site fluid leakage, puncture site skin allergy, and deep vein thrombosis were significantly lower than those in the CVC group [puncture site fluid leakage: 1.9% (1/52) vs. 22.1% (49/222), puncture site skin allergy: 0% (0/52) vs. 20.7% (46/222), deep vein thrombosis: 3.8% (2/52) vs. 16.7% (37/222), all P < 0.05]. Furthermore, the proportion of patients experiencing three or more types of complications in the MMC group was significantly lower than that in the CVC group [5.8% (3/52) vs. 17.6% (39/222), P < 0.05]. Multivariate Logistic regression analysis of risk factors for catheter removal identified the use of a MMC [odds ratio (OR) = 8.518, 95% confidence interval (95%CI) was 3.710-19.560, P < 0.001] and a catheter indwelling time ≥ 12 days (OR = 3.133, 95%CI was 1.297-7.567, P = 0.011) as independent risk factors. CONCLUSIONS MMC was more frequently used in patients with ARDS, cardiovascular disease, and cancer, whereas CVC was primarily employed for vasoactive drug infusion. The use of MMC and a longer indwelling time were identified as independent risk factors for catheter removal. Despite a higher removal rate, the overall incidence of complications was significantly lower with MMC than with CVC. These findings suggest that MMC could serve as a routine alternative to CVC in most of clinical scenarios, provided that measures are implemented to prevent removal.
Humans ; Retrospective Studies ; Intensive Care Units ; Catheterization, Central Venous/methods* ; Central Venous Catheters ; Risk Factors ; Length of Stay ; Male ; Female ; Middle Aged ; Adult ; Catheters, Indwelling ; Aged

Objective To explore the diagnostic value of energy spectrum CT quantitative parameters combined with serum thy-roid stimulating hormone receptor-messenger ribonucleic acid(TSHR-mRNA)for papillary thyroid microcarcinoma(PTMC).Methods A total of 105 patients with thyroid micronodules confirmed by surgery and pathology were collected,61 of whom were PTMC(PTMC group),and 44 patients with micronodular goiter(MNG)(MNG group).Energy spectrum CT quantitative parameters and serum TSHR-mRNA expression were compared between the two groups.The diagnostic value of energy spectrum CT quantitative parame-ters alone and combined with serum TSHR-mRNA for PTMC was analyzed by receiver operating characteristic(ROC)curve.Results The iodine concentration and slope of energy spectrum CT quantitative parameters between PTMC group and MNG group were signifi-cantly different in plain scan,arterial and venous phases(P＜0.05).The mean serum TSHR-mRNA expression in the PTMC group was higher than that in MNG group(P＜0.05).The area under the curve(AUC)for diagnosing PTMC using quantitative parame-ters of energy spectrum CT combined with serum TSHR-mRNA was 0.913,and the accuracy,sensitivity,and negative predictive value of diagnosing PTMC were significantly higher than those of quantitative parameters of energy spectrum CT or serum TSHR-mRNA(P＜0.05).Conclusion Both energy spectrum CT quantitative parameters and serum TSHR-mRNA can be used to diagnose PTMC alone,and the combination of both is more accurately.

OBJECTIVE: To identify the protective effect of empagliflozin on ischemic brain injury and neurological dysfunction in mice, and further explore its potential mechanism. METHODS: Acute cerebral ischemia model was induced by the permanent middle cerebral artery occlusion surgery in C57BL/6J mice. Empagliflozin(10 and 30 mg·kg−1) was administered to mice one hour after the onset of occlusion. Brain infarct volume and neurological defect score were assayed 24 h after surgery. Mice were subjected to photo-thrombosis and further administered with empagliflozin 3, 10, 30 mg·kg−1 intragastricly for either 7 or 14 consecutive days. The grid-walking task and the cylinder task were performed daily to determine the sensory-motor function of the mice. Alternatively, the mice were treated with 10 mg·kg−1 empagliflozin simultaneously with 10% glucose(i.p.) for 7 consecutive days after the photo-thrombosis model to evaluate their motor sensory function. Immunofluorescence staining was used to detect the activation of microglia within the infarct area 7 d after the photo-thrombosis. RESULTS: One hour after permanent middle cerebral artery occlusion surgery, gavage of empagliflozin significantly increased the brain infarct volume and neurological dysfunction. While in photo-thrombosis surgery, treatment of empagliflozin(10 mg·kg−1) for consecutive 7 or 14 days significantly decreased the rate of false foot in grid-walking task and the assymetric index in cylinder task. At the dose of 30 mg·kg−1, however, empagliflozin even aggravated photo-thrombosis-induced neurological dysfunction, while the dose of 3 mg·kg−1 showed no effect. Unexpectedly, the protective effect of empagliflozin(10 mg·kg−1) could not be reversed by glucose treatment. The results of immunofluorescence showed that empagliflozin(10 mg·kg−1) significantly alleviated the microglia activation in the ischemic area after the photo-thrombosis operation. CONCLUSION Empagliflozin cannot protect against acute ischemia-induced brain injury in mice. Empagliflozin alleviated ischemia-induced neurological dysfunction with consecutive administration in a dose-related manner. Empagliflozin-conferred neuroprotection may not be attributable to its effects on lowing blood glucose. Alternatively, empagliflozin may play a neuroprotective effect by inhibiting the excessive activation of microglia in ischemic brains.

ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang （HYT） on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group， a model group， a euthyrox group （20 μg·kg^-1）， a HYT group （12.06 g·kg^-1）， a HYT without Sargassum （HYT-H） group （9.90 g·kg^-1）， a HYT without Glycyrrhizae Radix et Rhizoma （HYT-G） group （10.26 g·kg^-1）， a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma （HYT-HG） group （8.10 g·kg^-1）， and a Sargassum and Glycyrrhizae Radix et Rhizoma （HG） group （3.96 g·kg^-1）. The blank group was given deionized water by gavage， and the others were given propylthiouracil （PTU） to replicate the goiter pathological model. Euthyrox was taken as a positive control drug， and the rest of the Chinese medicine groups were given the corresponding decoction by gavage， the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， and the contents of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， reactive oxygen species （ROS） in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 （Keap1）， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group， the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues （P<0.05， P<0.01）， significantly reduced activities of SOD and GSH-Px in the liver （P<0.01）， significantly increased mRNA expression of Keap1 （P<0.01）， and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. Compared with the model group， the HYT group manifested significantly reduced serum levels of AST， ALT， and ALP （P<0.05， P<0.01）， significantly reduced contents of MDA and ROS in liver tissue （P<0.01）， significantly increased the activities of SOD and GSH-Px （P<0.01）， significantly decreased mRNA expressions of Keap1， p53， and Caspase-3 （P<0.01）， and significantly increased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020， Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats， and the effect is better than that of the HG group， the euthyrox group， and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.

Objective:To investigate the clinicopathological and molecular genetic characteristics of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) with myxoid-like morphology, and to distinguish them from myxofibrosarcoma (MFS) with similar morphology.Methods:Twenty-nine cases of myxoid-like liposarcoma and 5 cases of MFS were collected from Henan Provincial People′s Hospital, Zhengzhou, China and the First Medical Center of PLA General Hospital, Beijing, China from January 2015 to March 2023. Relevant markers were detected using immunohistochemistry and fluorescence in situ hybridization (FISH). The literature was also reviewed.Results:There were 24 males and 10 females, with ages ranging from 41 to 73 years. The tumor sites included retroperitoneum ( n=17), abdomen ( n=9), lower limbs ( n=5), scrotum ( n=1), upper limb ( n=1) and axilla ( n=1). WDLPS was commonly seen as lipomatoid type (12 cases), while the dedifferentiated components of DDLPS included low-grade (13 cases) and high-grade (2 cases) morphology, with low-high grade myxofibrosarcoma, dermatofibrosarcoma protuberans, and low-grade fibrosarcoma structures. Twenty-nine liposarcomas had various proportions of myxoid-like morphology, while 16 showed various degrees of tumor necrosis. The myxoid-like component showed myxoid pleomorphic liposarcoma (MLPS)-like morphology, lobulated growth, characteristic slender, ramified capillary network,"chicken claw-like"morphology, mucus-rich stroma and lung edema-like morphology. Tumor cells were spindle and oval, with many variable vacuolar lipoblasts. MDM2 gene amplification was detected using FISH and present in all tested cases (29/29). DDIT3 break-apart mutation was not detected, but its cluster amplification was present (24/29). Among the MFS cases, one showed cluster amplification (1/5), but no cases showed break-apart or amplification of MDM2 gene. Conclusions:WDLPS/DDLPS with myxoid-like morphology is most commonly seen in the retroperitoneum and abdominal cavity and mostly harbors DDIT3 break-apart probe amplification, while this amplification is not specific to liposarcoma. For core biopsy specimens or very rare tumors in the limbs, when histology has mucinous stroma and MLPS-like morphology, misdiagnosis of MLPS or other non-lipomatous neoplasms with myxoid morphology should be avoided.