MedChatZH: A tuning LLM for traditional Chinese medicine consultations.

Generative Large Language Models (LLMs) have achieved significant success in various natural language processing tasks, including Question-Answering (QA) and dialogue systems. However, most models are trained on English data and lack strong generalization in providing answers in Chinese. This limitation is especially evident in specialized domains like traditional Chinese medical QA, where performance suffers due to the absence of fine-tuning and high-quality datasets. To address this, we introduce MedChatZH, a dialogue model optimized for Chinese medical QA based on transformer decoder with LLaMA architecture. Continued pre-training on a curated corpus of Chinese medical books is followed by fine-tuning with a carefully selected medical instruction dataset, resulting in MedChatZH outperforming several Chinese dialogue baselines on a real-world medical dialogue dataset. Our model, code, and dataset are publicly available on GitHub (https://github.com/tyang816/MedChatZH) to encourage further research in traditional Chinese medicine and LLMs.

Shaoyao Gancao Decoction protects against dextran sulfate sodium-induced ulcerative colitis by down-regulating ferroptosis.

OBJECTIVES: Shaoyao Gancao Decoction (SGD) is a well-known Chinese herbal prescription used to treat ulcerative colitis (UC). This study was designed to evaluate the effect of SGD in dextran sulfate sodium-induced UC and to reveal the potential mechanism. METHODS: A UC mouse model was established by the administration of dextran sulfate sodium. The mice were given SGD extract intragastrically for 7 days. Histological pathology, inflammatory factors, and ferroptosis regulators were determined in vivo. In addition, ferroptotic Caco-2 cells were prepared to investigate the underlying mechanism of the effects of SGD. KEY FINDINGS: The results showed that SGD reduced the disease activity index, the level of inflammatory factors, and histological damage in mice with UC. Moreover, SGD down-regulated the level of ferroptosis in cells in colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production, compared with the model group. Correspondingly, similar effects of SGD on ferroptosis were observed in Erastin-treated Caco-2 cells. The results of our in vitro reactive oxygen species assays and the changes in mitochondrial structure observed by scanning electron microscopy also supported these results. CONCLUSION: Taken together, these findings suggest that SGD protected against UC by down-regulating ferroptosis in colonic tissue.

The effects of natural products and bioactive ingredients of traditional Chinese medicine on apoptosis of ovarian granulosa cells.

Abnormal ovarian function is the main manifestation of female reproductive toxicity. Granulosa cells (GCs) play an important role in determining the fate of follicles and are the main effector cells of the female reproductive system. Excessive apoptosis of GCs leads to pathological folliculogenesis and further reproductive damage. However, drugs available for treatment of female reproductive toxicity are limited. Recent studies have confirmed that various natural products and bioactive ingredients of traditional Chinese medicine (TCM) can inhibit apoptosis of GCs and protect ovarian function. In this review, the mechanisms underlying the proapoptotic and antiapoptotic effects of natural products and bioactive ingredients of TCM on the proliferation, function, and apoptosis of GCs are summarized based on the findings of reports published over the past 10 years as reference for the treatment of female reproductive toxicity.

TMT-based quantitative proteomics analysis of the effects of Jiawei Danshen decoction myocardial ischemia-reperfusion injury.

BACKGROUND: Every year, approximately 17 million people worldwide die due to coronary heart disease, with China ranking second in terms of the death toll. Myocardial ischemia-reperfusion injury (MIRI) significantly influences cardiac function and prognosis in cardiac surgery patients. Jiawei Danshen Decoction (JWDSD) is a traditional Chinese herbal prescription that has been used clinically for many years in China to treat MIRI. The underlying molecular mechanisms, however, remain unknown. To investigate the proteomic changes in myocardial tissue of rats given JWDSD for MIRI therapy-based proteomics. METHODS: MIRI rat model was created by ligating/releasing the left anterior descending coronary artery. For seven days, the drugs were administered twice daily. The model was created following the last drug administration. JWDSD's efficacy in improving MIRI was evaluated using biochemical markers and cardiac histology. Tandem mass tag-based quantitative proteomics (TMT) technology was also used to detect proteins in the extracted heart tissue. To analyze differentially expressed proteins (DEPs), bioinformatics analysis, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways, were employed. Furthermore, western blotting confirmed the potential targets regulated by JWDSD. RESULTS: The histopathologic characteristics and biochemical data showed JWDSD's protective effects on MIRI rats. A total of 4549 proteins were identified with FDR (false discovery rate) ≤1%. Twenty overlapping were identified (162 DEPs and 45 DEPs in Model/Control or JWDSD/Model group, respectively). Of these DEPs, 16 were regulated by JWDSD. GO analysis provided a summary of the deregulated protein expression in the categories of biological process (BP), cell component (CC), and molecular function (MF). KEGG enrichment analysis revealed that the signaling pathways of neutrophil extracellular trap formation, RNA polymerase, serotonergic synapse, and linoleic acid metabolism are all closely related to JWDSD effects in MIRI rats. Furthermore, T-cell lymphoma invasion and metastasis 1 (TIAM1) was validated using western blotting, and the results were consistent with proteomics data. CONCLUSIONS: Our study suggests that JWDSD may exert therapeutic effects through multi-pathways regulation in MIRI treatment. This work may provide proteomics clues for continuing research on JWDSD in treating MIRI.

Paeoniflorin Protects H9c2 Cardiomyocytes against Hypoxia/Reoxygenation Induced Injury via Regulating the AMPK/Nrf2 Signaling Pathway.

Myocardial ischemia/reperfusion (MIR) injury contributes to the exacerbation of heart disease by causing cardiac arrhythmias, myocardial infarction, and even sudden death. Studies have found that paeoniflorin (PF) has a protective effect on coronary artery disease (CAD). However, the mechanism of PF in MIR has not been fully investigated. The purpose of this study was to investigate the functional role of PF in H9c2 cells subjected to hypoxia/reoxygenation (H/R). Here, PF treatment enhanced cell viability in H/R-stimulated H9c2 cells. In H9c2 cells, PF treatment reduced the formation of reactive oxygen species (ROS) induced by H/R. In H/R-stimulated H9c2 cells, PF also increased the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. Furthermore, PF protected H9c2 cells against H/R-induced apoptosis, as demonstrated by increased Bcl-2 expression, decreased Bax expression, and decreased caspase-3 activity. Furthermore, PF increased the levels of p-AMPK and nuclear Nrf2 expression in response to H/R stimulation. AMPK inhibition, on the other hand, abolished the PF-mediated increase in Nrf2 signaling and the cardiac-protective effect in H9c2 cells exposed to H/R. These data suggest that PF protected H9c2 cells against H/R-induced oxidative stress and apoptosis through modulating the AMPK/Nrf2 signaling pathway. Our findings support the therapeutic potential of PF in myocardial I/R damage.

Photodynamic Therapy with Tumor Cell Discrimination through RNA-Targeting Ability of Photosensitizer.

Photodynamic therapy (PDT) represents an effective treatment to cure cancer. The targeting ability of the photosensitizer is of utmost importance. Photosensitizers that discriminate cancer cells can avoid the killing of normal cells and improve PDT efficacy. However, the design and synthesis of photosensitizers conjugated with a recognition unit of cancer cell markers is complex and may not effectively target cancer. Considering that the total RNA content in cancer cells is commonly higher than in normal cells, this study has developed the photosensitizer QICY with RNA-targeting abilities for the discrimination of cancer cells. QICY was specifically located in cancer cells rather than normal cells due to their stronger electrostatic interactions with RNA, thereby further improving the PDT effects on the cancer cells. After intravenous injection into mice bearing a xenograft tumor, QICY accumulated into the tumor location through the enhanced permeability and retention effect, automatically targeted cancer cells under the control of RNA, and inhibited tumor growth under 630 nm laser irradiation without obvious side effects. This intelligent photosensitizer with RNA-targeting ability not only simplifies the design and synthesis of cancer-cell-targeting photosensitizers but also paves the way for the further development of highly efficient PDTs.

Complete Response of Hepatocellular Carcinoma with Macroscopic Vascular Invasion and Pulmonary Metastasis to the Combination of Drug-Eluting Beads Transarterial Chemoembolization and Huaier Granule: A Case Report.

BACKGROUND: Hepatocellular carcinoma (HCC) associated with macroscopic vascular invasion and distant metastasis is an advanced-stage disease with an extremely poor prognosis and low survival rate. Therefore, there is an urgent need to develop novel therapeutic strategies to extend the lives of patients with advanced HCC. CASE PRESENTATION: We represent a case of HCC with macroscopic vascular invasion and pulmonary metastasis responding dramatically to the combination treatment with drug-eluting beads transarterial chemoembolization (DEB-TACE) and Huaier granule. A 64-year-old man with hepatitis B virus (HBV)-induced liver cirrhosis was diagnosed with advanced HCC involved renal vein and inferior vena cava accompanied by pulmonary metastasis. The patient received three cycles of on-demand DEB-TACE from 9th September 2016 to 22nd August 2017 and combined with Huaier granule 20 g three times a day orally. Eight months following the treatment, complete response occurred with regression of HCC and vascular thrombus and disappearance of pulmonary metastasis. The levels of AFP had decreased from 8165.8ng/mL to within the normal range (1.7 ng/mL). This is the first case report of complete response of HCC to the combination treatment with DEB-TACE and Huaier granule. At the most recent follow-up, he remained in remission 36 months after cessation of treatment without clinical or imaging evidence of disease recurrence. The current overall survival is 54 months since the initial treatment. CONCLUSION: Data from this clinical case report suggest that the combination treatment with DEB-TACE and Huaier granule is a promising therapeutic option for advanced HCC with macroscopic vascular invasion and distant metastasis.

Vacancy-Induced Antibacterial Activity of XS2-y Quantum Dots against Drug-Resistant Bacteria for Treatment of Bacterial Keratitis.

Due to the widespread antibiotic-resistant microbes and the slow development in antibiotics, innovative new antibacterial agents are eagerly desired to control infection in the resistance era. Here, it is demonstrated that the antibacterial ability against drug-resistant bacteria can be endowed to transition metal dichalcogenides (XS2 , X = Mo/W) quantum dots by sulfur vacancies, and their application in bacterial keratitis. The sulfur vacancies are generated by the ion irradiation with the controlled influences, which ensures the one-way electron transport from the external environment to XS2 leading to a strong reactive oxygen speciesindependent oxidative stress. With the concentration of 140 µg mL-1 of XS2-0.1 quantum dots, the sterilization efficiency of Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus more than 99.9% within 20 min at room temperature in the dark is realized. For biomedical application against bacterial keratitis, it is observed that the occurrence of severe clinical manifestation like ocular perforation can be prevented. This work demonstrates the vacancy as a novel, simple, and effective strategy to tune XS2 as the antibacterial agent with a fast response and no reliance on light that has significant potential therapeutic effects on clinical drug resistant bacterial keratitis.

Administration of a mixture of triterpenoids from yeyachun and phenolic acids from danshen ameliorates carbon tetrachloride-induced liver fibrosis in mice by the regulation of intestinal flora.

yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl4) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl4 induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.

Theranostic Nanomedicine Carrying L-Menthol and Near-Infrared Dye for Multimodal Imaging-Guided Photothermal Therapy of Cancer.

Photothermal therapy (PTT) as an emerging technique for cancer treatment has drawn great attention owing to its minimally invasive nature. However, it is difficult to achieve a complete tumor regression due to the heterogeneous heat distribution over the tumor. Application of photothermal conversion agents may enhance PTT efficiency, and a multifunctional imaging may provide guidance for the implementation of PTT. Herein, an L-menthol/IR-780 loaded liposome (MIL) is prepared to achieve NIR-triggered cavitation for enhancing photothermal ablation. The synthesized MIL possesses outstanding colloidal stability and photoacoustic/near infrared fluorescence/ultrasound (PA/NIRF/US) imaging contrast to offer multimodal imaging-guided photothermal therapy of cancer. Upon irradiation, the IR-780 acts as the photoabsorber to convert NIR light into heat energy. More importantly, the produced hyperthermia can not only induce ablation of tumor cells but also trigger vaporization and bubbling of encapsulated L-menthol (menthol). Consequently, the generated menthol bubbles obviously enhance the US imaging signal and promote photothermal ablation of the tumor.

Mindful exercise versus non-mindful exercise for schizophrenia: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate whether the mindful exercise was more beneficial than non-mindful exercise for people with schizophrenia. METHODS: PubMed, Embase, Cochrane Library, and PsycINFO were searched from their onset to April 2017. Randomized controlled trials of schizophrenia were selected. Mindful exercises were yoga, tai chi or qigong. Non-mindful exercises included any type of purely physical exercise. Risk of bias was assessed using criteria in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Seven studies were identified. There were significant differences in favour of mindful exercise in psychiatric symptoms (total PANSS, 2 RCT, n = 101, MD -8.94, low-quality evidence) and "working memory" (1 RCT, n = 194, MD 0.39, low-quality). For outcomes of "attention" and social functioning, there was no clear difference. Four studies reported no adverse events. CONCLUSIONS: Mindful exercise was more beneficial over non-mindful exercise on some outcomes of psychiatric symptoms and cognitive performance for schizophrenia.

Investigation and analysis of the characteristics and drug sensitivity of bacteria in skin ulcer infections.

PURPOSE: Skin ulcer is a common type of disease affecting patients' health and quality of life, and bacterial infection increases the difficulty of its management. METHODS: The present study collected the results of bacterial culture sampled from the surface of 110 cases of skin ulcers at our hospital from January 2011 to December 2012. We analyzed the constituent ratios of ulcer surface bacteria, the change in the main infectious bacteria and the results of drug-sensitivity testing for common bacteria. In addition, the characteristics of bacterial infection of skin ulcers were summarized. RESULT: Of the 110 samples, 90 isolated bacteria were cultured. Sixty-one were Gram-negative bacteria, mainly comprising Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae and Escherichia coli. In addition, 23 isolates were Gram-positive bacteria, mainly comprising Staphylococcus aureus and Enterococcus faecalis. The probability of a negative bacterial culture in 2012 was significantly lower than that in 2011 (16.7% vs. 40.0%, p < 0.01). Moreover, the probability of P. aeruginosa infection in 2012 was significantly higher than that in 2011 (31.7% vs. 14.0%, p < 0.01). P. aeruginosa was resistant to seven commonly used antibiotics. Both K. pneumoniae and E. coli had higher resistance to ampicillin. E. cloacae were not sensitive to piperacillin/tazobactam. Acinetobacter baumannii was resistant to all the tested drugs. S. aureus, E. faecalis and Staphylococcus epidermidis had high resistance to clindamycin. There was other drug resistance to reflect the higher rate of skin bacterial resistance. CONCLUSION: Skin bacterial resistance rate is high. Gram-negative bacteria gradually account for the majority, and P. aeruginosa becomes the most important skin infection pathogen. These characteristics of bacterial infections of skin ulcers provide a significant reference for guiding the selection of antibiotics, better controlling infections of skin ulcers and accelerating the healing of skin ulcers.

Thermal Preconditioning May Prevent Tendon Adhesion by Up-Regulating HSP72 in Rats.

BACKGROUND/AIMS: The study aims to determine the effects of thermal preconditioning on tendon adhesion by regulating the expression of heat shock protein 72 (HSP72) in rat models. METHODS: Sixty male Wistar rats were collected and randomly assigned into the thermal preconditioning and control groups. During the 4th and 8th weeks following surgery, 15 rats were sacrificed in each period respectively, and their tendon adhesion was observed and evaluated. Biomechanical testing was performed to measure the tensile strength and gliding distance of tendons. Hematoxylin-eosin (HE) was used to observe the morphological structure of the tendons. Immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the HSP72, fibroblast growth factor-2 (FGF-2), fibroblast growth factor receptor-1 (FGFR-1), ß-catenin, epithelial cell adhesion molecule (EPCAM), Tenomodulin and scleraxis protein expressions. Pearson correlation analysis was applied to analyze the correlation between HSP72 expression and tendon adhesion. RESULTS: At the 4th week after surgery, we found no differences in the tendon adhesion scores or mRNA and protein expressions of HSP72 between the thermal preconditioning and control groups. However, after the 8th week after surgery, the thermal preconditioning group had a lower tendon adhesion score and higher mRNA and protein expressions of HSP72 than the control group. During the same period, we found longer gliding distance and higher expression levels of FGF-2, FGFR-1, ß-catenin, Tenomodulin and scleraxis, but lower EPCAM expression in the thermal preconditioning group. Pearson correlation analysis indicated that HSP72 mRNA and protein expression levels were negatively correlated with tendon adhesion. CONCLUSIONS: These findings provide evidence that thermal preconditioning may alleviate tendon adhesions via upregulation of HSP72 expression.

Andrographolide alleviates imiquimod-induced psoriasis in mice via inducing autophagic proteolysis of MyD88.

Psoriasis is a chronic inflammatory skin disease with excessive activation of toll-like receptors (TLRs), which play important roles in developing psoriasis. Targeting TLR signaling remains a challenge for treating psoriasis. Here, we found that andrographolide (Andro), a small-molecule natural product, alleviated imiquimod- but not interleukin 23 (IL-23)-induced psoriasis in mice with reducing expressions of IL-23 and IL-1ß in the skin. The improvement in imiquimod-induced psoriasis by Andro was not observed in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) knockout mice. Furthermore, Andro inhibited mRNA expressions of IL-23, IL-6 and IL-1ß but not CD80 and CD86 in bone-marrow derived dendritic cells (BMDCs) treated with lipopolysaccharide (LPS) in a MAP1LC3B-dependent manner. In addition, Andro inhibited imiquimod-induced mRNA expressions of IL-23, IL-6, IL-1ß, CD80 and CD86 in BMDCs from mice. Interestingly, Andro induced a degradation of myeloid differentiation factor 88 (MyD88) and blocked the recruitment of TNF receptor-associated factor 6 (TRAF6) to MyD88 upon LPS stimulation in BMDCs from mice. Blockade of autophagic proteolysis using NH4Cl or MAP1LC3B(-/-) BMDCs abolished the Andro-induced MyD88 degradation. In conclusion, Andro controls activation of MyD88-dependent cytokines and alleviates psoriasis in mice via inducing autophagic proteolysis of MyD88, which could be a novel strategy to treat psoriasis.

Transcatheter Arterial Embolization Alone for Giant Hepatic Hemangioma.

Giant hepatic hemangioma is a benign liver condition that may be treated using surgery. We studied the digital subtraction angiographic (DSA) characteristics of giant hepatic hemangioma, and the effectiveness of transcatheter arterial embolization (TAE) alone for its treatment. This was a retrospective study of 27 patients diagnosed with giant hepatic hemangioma and treated with TAE alone (using lipiodol mixed with pingyangmycin) at the Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University, between January 2010 and March 2013. The feeding arteries were identified using DSA. All patients were followed up for between three weeks and 12 months. Changes in tumor diameter and symptoms were observed. The 27 patients included had giant hepatic hemangiomas ranging from 5.3 to 24.5 cm (mean, 11.24±5.08 cm) in the right (n = 13), left (n = 1) or both (n = 13) lobes. Preoperative hepatic angiography showed multiple abnormal vascular lakes in the early phase, known as the "early leaving but late returning, hanging nut on a twig" sign. On the day after TAE, hepatic transaminase levels were increased (ALT: 22.69±17.95 to 94.88±210.32 U/L; ALT: 24.00±12.37 to 99.70±211.54 U/L; both P<0.05), but not total bilirubin. Six patients complained of abdominal pain, and 12 experienced transient fever. In the months after TAE, tumor size decreased (baseline: 11.24±5.08; 3 months: 8.95±4.33; 6 months: 7.60±3.90 cm; P<0.05), and the patients' condition improved. These results indicated that TAE was effective and safe for treating giant hepatic hemangioma. TAE may be a useful alternative to surgery for the treatment of hepatic hemangioma.

Effect of Angelica sinensis Polysaccharides on Osteoarthritis In Vivo and In Vitro: A Possible Mechanism to Promote Proteoglycans Synthesis.

This study investigated the effect of Angelica sinensis polysaccharides (APS-3c) on rat osteoarthritis (OA) model in vivo and rat interleukin-1-beta- (IL-1 ß -) stimulated chondrocytes in vitro. APS-3c was administrated into rat OA knee joints and had protective effects on rat OA cartilage in vivo. Primary rat articular chondrocytes were cotreated with APS-3c and IL-1 ß in vitro. 2~50 µ g/mL APS-3c had no effect on chondrocytes viability, whereas it increased the proteoglycans (PGs) synthesis inhibited by IL-1 ß . Microarray analysis showed that the significant changes were concentrated in the genes which were involved in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1 ß but did not affect the mRNA expression of matrix-degrading enzymes. These results indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA model in vivo and IL-1 ß -stimulated chondrocytes in vitro, which is due to the promotion of the expression of aggrecan and GTs involved in PGs synthesis but not the inhibition of the expression of matrix-degrading enzymes. Our findings suggest the clinical relevance of APS-3c in the prospective of future alternative medical treatment for OA.