A thermoresponsive nanocomposite integrates NIR-II-absorbing small molecule with lonidamine for pyroptosis-promoted synergistic immunotherapy.

Photothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our "two-step" donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M-1 cm-1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors.

Neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable hepatocellular carcinoma: the Notable-HCC phase 1b trial.

Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.

HAIC Combined with lenvatinib plus PD-1 versus lenvatinib Plus PD-1 in patients with high-risk advanced HCC: a real-world study.

BACKGROUND: The treatment of hepatocellular carcinoma (HCC) patients exhibiting high-risk characteristics (Vp4, and/or bile duct invasion, and/or tumor occupancy ≥ 50%) lacks standardized approaches and yields unfavorable results. This study endeavors to evaluate the safety, efficacy, and prognostic impacts of employing hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1 (PD-1) in the treatment of high-risk HCC patients. METHODS: In this retrospective analysis, HCC patients with high-risk features were treated with either lenvatinib combined with PD-1 (LEN-PD1) or a combination of HAIC, lenvatinib, and PD-1 (HAIC-LEN-PD1). The study assessed the antitumor efficacy by calculating overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. RESULTS: Between June 2019 and September 2022, a total of 61 patients were included in the LEN-PD1 group, while 103 patients were enrolled in the HAIC-LEN-PD1 group. The OS was 9.8 months in the LEN-PD1 group, whereas the HAIC-LEN-PD1 group exhibited a significantly longer median OS of 19.3 months (HR = 0.43, p < 0.001). Furthermore, PFS was notably extended in the HAIC-LEN-PD1 group compared to the LEN-PD1 group (9.6 months vs. 4.9 months, HR = 0.48, p < 0.001). Patients in the HAIC-LEN-PD1 group had a higher ORR and DCR according to the modified RECIST (76.7% vs. 23.0%, p < 0.001; 92.2% vs. 72.1%, p = 0.001). HAIC-LEN-HAIC group led to more adverse events than LEN-PD1 group, most of which were tolerable and controllable. CONCLUSION: Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features.

Diagnostic value of a novel salivary gland ultrasound scoring system in IgG4-related sialadenitis.

OBJECTIVES: To develop a novel ultrasound scoring system for the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and assess its diagnostic value in a multicenter cohort of Chinese patients. METHODS: Twenty clinicians (rheumatologists, stomatologists, and radiologists) participated. The study was conducted in four steps: (1) defining the ultrasonography (US) elements, (2) developing a novel ultrasound scoring system for US of the salivary glands, (3) evaluation of inter- and intra-reader reliabilities using the new ultrasound scoring system, and (4) assessing the diagnostic value of this novel ultrasound scoring system in IgG4-RS patients in a Chinese multicenter cohort. RESULTS: A novel ultrasound scoring system for the salivary glands was developed, with total scores ranging from 0 to 34. The inter- and intra-reader reliabilities of the ultrasound scoring system were excellent (0.972 and 0.940, respectively). A total of 470 people were recruited in this study; 187 patients were diagnosed with IgG4-RS, and the remaining 283 people were diagnosed with non-IgG4-RS. Patients with IgG4-RS had significantly higher US scores than the non-IgG4-RS group (mean US score=16 vs. 4, P < 0.001). The calculated area under the curve (AUC) for the total US score was 0.852 (95% CI: 0.814-0.891). The total US scores≥9 showed a sensitivity of 75.4% and a specificity of 91.9%. Association analysis showed a positive correlation between total US scores and serum IgG4 levels and hypocomplementemia (r=0.221, r=0.349; P = 0.002) and a negative correlation between total US scores and serum C3 and C4 levels (r=-0.210, r=-0.303; P = 0.005, P < 0.001). CONCLUSIONS: A novel semiquantitative ultrasound scoring system for patients with IgG4-RS was developed, with good diagnostic performance. The inter- and intra-reader reliabilities were excellent. US scores were correlated with IgG4, C3, and C4 levels and hypocomplementemia.

The potential role of the triglyceride-glucose index in left ventricular systolic function and in-hospital outcomes for patients with acute myocardial infarction.

BACKGROUND: A limited number of small-sample cohort studies have investigated the association between the triglyceride-glucose index and in-hospital prognosis. Moreover, the translational potential role of left ventricular systolic function - measured by left ventricular ejection fraction - combined with the triglyceride-glucose index in prioritizing patients with acute myocardial infarction at high risk of in-hospital major adverse cardiovascular events remains unknown. AIM: To explore the potential role of the triglyceride-glucose index in left ventricular systolic function and in-hospital major adverse cardiovascular events in patients with acute myocardial infarction. METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project (CCC-ACS) was analysed for this study. RESULTS: We included 43,796 patients with acute myocardial infarction. Patients with a higher triglyceride-glucose index showed an increased risk of major adverse cardiovascular events (adjusted odds ratio 1.46, 95% confidence interval 1.31-1.63). Interaction analyses revealed that left ventricular ejection fraction modified the relationship between the triglyceride-glucose index and major adverse cardiovascular events. Furthermore, patients with acute myocardial infarction were categorized by the triglyceride-glucose index and left ventricular ejection fraction; the low left ventricular ejection fraction/high triglyceride-glucose index group showed the highest risk of major adverse cardiovascular events (adjusted odds ratio 2.14, 95% confidence interval 1.58-2.89). CONCLUSIONS: In a comprehensive nationwide acute myocardial infarction registry conducted in China, a higher triglyceride-glucose index was found to be associated with in-hospital major adverse cardiovascular events, and this was particularly evident among patients with a lower left ventricular ejection fraction. Moreover, the triglyceride-glucose index combined with left ventricular ejection fraction was helpful for risk stratification of patients with acute myocardial infarction.

The impact of modifiable health metrics on mortality for older adults with low cognitive function.

Objectives: Cognitive impairment has emerged as a major contributing factor to mortality for older adults. Identifying the strong modifiable health metrics against mortality is of high priority, especially in this high-risk population. Methods: This population-based study used data of US adults aged≥60 years old from the National Health and Nutrition Examination Survey 2011-2014 cycles. De-identified data for participants who completed cognitive function test were extracted. Mortality data was obtained by linking to the 2019 public-use linked mortality file. Results: Participants with low global cognition had higher risk of all-cause mortality (HR = 1.46; 95%CI, 1.04-2.05). The highest prevalence of ideal level of health metrics was observed for sleep duration (54.36% vs. 62.37%), and the lowest was noted for blood pressure (12.06% vs. 21.25%) for participants with low and average to high global cognition, respectively. Ideal status of physical activity and diet quality were significantly associated with all-cause mortality among participants with low global cognition (HR = 0.48, 95%CI: 0.28-0.82; HR = 0.63, 95%CI: 0.43-0.95). The corresponding population-attributable fractions were 26.58 and 15.90%, respectively. Conclusion: Low cognitive function was associated with increased risk of all-cause death for older adults. Attainment of healthy metrics, especially sufficient physical activity, consuming healthy diet and being never smoked, provided strong protection against death risk.

Assessing the role of GPT-4 in thyroid ultrasound diagnosis and treatment recommendations: enhancing interpretability with a chain of thought approach.

Background: As artificial intelligence (AI) becomes increasingly prevalent in the medical field, the effectiveness of AI-generated medical reports in disease diagnosis remains to be evaluated. ChatGPT is a large language model developed by open AI with a notable capacity for text abstraction and comprehension. This study aimed to explore the capabilities, limitations, and potential of Generative Pre-trained Transformer (GPT)-4 in analyzing thyroid cancer ultrasound reports, providing diagnoses, and recommending treatment plans. Methods: Using 109 diverse thyroid cancer cases, we evaluated GPT-4's performance by comparing its generated reports to those from doctors with various levels of experience. We also conducted a Turing Test and a consistency analysis. To enhance the interpretability of the model, we applied the Chain of Thought (CoT) method to deconstruct the decision-making chain of the GPT model. Results: GPT-4 demonstrated proficiency in report structuring, professional terminology, and clarity of expression, but showed limitations in diagnostic accuracy. In addition, our consistency analysis highlighted certain discrepancies in the AI's performance. The CoT method effectively enhanced the interpretability of the AI's decision-making process. Conclusions: GPT-4 exhibits potential as a supplementary tool in healthcare, especially for generating thyroid gland diagnostic reports. Our proposed online platform, "ThyroAIGuide", alongside the CoT method, underscores the potential of AI to augment diagnostic processes, elevate healthcare accessibility, and advance patient education. However, the journey towards fully integrating AI into healthcare is ongoing, requiring continuous research, development, and careful monitoring by medical professionals to ensure patient safety and quality of care.

Spontaneous multivessel coronary artery spasm: a case report.

A 60-year-old male presented to the emergency department of our hospital with persistent dull pain in the lower and middle sternum with generalized sweating after a heated argument with another person, and his symptoms did not resolve after 3 hours of onset.

Quantitative ultrasound parameters from scattering and propagation may reduce the biopsy rate for breast tumor.

Breast cancer has become the most common cancer worldwide, and early screening improves the patient's survival rate significantly. Although pathology with needle-based biopsy is the gold standard for breast cancer diagnosis, it is invasive, painful, and expensive. Meanwhile it makes patients suffer from misplacement of the needle, resulting in misdiagnosis and further assessment. Ultrasound imaging is non-invasive and real-time, however, benign and malignant tumors are hard to differentiate in grayscale B-mode images. We hypothesis that breast tumors exhibit characteristic properties, which generates distinctive spectral patterns not only in scattering, but also during propagation. In this paper, we propose a breast tumor classification method that evaluates the spectral pattern of the tissues both inside the tumor and beneath it. First, quantitative ultrasonic parameters of these spectral patterns were calculated as the representation of the corresponding tissues. Second, parameters were classified by the K-Nearest Neighbor machine learning model. This method was verified with an open access dataset as a reference, and applied to our own dataset to evaluate the potential for tumors assessment. With both datasets, the proposed method demonstrates accurate classification of the tumors, which potentially makes it unnecessary for certain patients to take the biopsy, reducing the rate of the painful and expensive procedure.

Risk and effect modifiers for poor glycemic control among the chinese diabetic adults on statin therapy: the kailuan study.

BACKGROUND: Limited studies have investigated the association between statin therapy and poor glycemic control, especially in the Chinese diabetic population. METHODS: Two prospective diabetes cohorts were drawn from the Kailuan Cohort. In Cohort 1, linear regression models were used to evaluate the association between statin therapy and glycated hemoglobin (HbA1c) level change. In Cohort 2, new user design and conditional logistic models were used to assess associations between statin initiation and poor glycemic control which was a composite outcome comprised of hypoglycemic agent escalation and new-onset hyperglycemia. RESULTS: Among 11,755 diabetic patients with medication information, 1400 statin users and 1767 statin nonusers with repeated HbA1c measurements were included in Cohort 1 (mean age: 64.6 ± 10.0 years). After a median follow-up of 3.02 (1.44, 5.00) years, statin therapy was associated with higher HbA1c levels (ß: 0.20%; 95%CI: 0.05% to 0.34%). In Cohort 2, 1319 pairs of matched cases/controls were included (mean age: 61.6 ± 9.75 years). After a median follow-up of 4.87 (2.51, 8.42) years, poor glycemic control occurred in 43.0% of statin new users and 31.8% of statin nonusers (OR: 1.69; 95% CI: 1.32 to 2.17; P < 0.001). The statin-associated poor glycemic control risk was significantly higher among patients with lower body mass index (Pint = 0.089). Furthermore, a nonlinear association was observed between statin therapy duration and poor glycemic control (P = 0.003). CONCLUSIONS: Among Chinese diabetic adults, statin therapy was associated with a higher level of HbA1c, and a higher risk of hypoglycemic agent escalation and new-onset hyperglycemia, especially among those who had lower body mass index levels and longer statin therapy duration.

Mechanism of Self-Oxidative Copolymerization and its Application with Polydopamine-pyrrole Nano-copolymers.

Currently, the copolymer of dopamine (DA) and pyrrole (PY) via chemical and electrochemical oxidation usually requires additional oxidants, and lacks flexibility in regulating the size and morphology, thereby limiting the broad applications of DA-PY copolymer in biomedicine. Herein, the semiquinone radicals produced by the self-oxidation of DA is ingeniously utilized as the oxidant to initiate the following copolymerization with PY, and a series of quinone-rich polydopamine-pyrrole copolymers (PDAm -nPY) with significantly enhanced absorption in near-infrared (NIR) region without any additional oxidant assistance is obtained. Moreover, the morphology and size of PDAm -nPY can be regulated by changing the concentration of DA and PY, thereby optimizing nanoscale PDA0.05 -0.15PY particles (≈ 150 nm) with excellent NIR absorption and surface modification activity are successfully synthesized. Such PDA0.05 -0.15PY particles show effective photoacoustic (PA) imaging and photothermal therapy (PTT) against 4T1 tumors in vivo. Furthermore, other catechol derivatives can also copolymerize with PY under the same conditions. This work by fully utilizing the semiquinone radical active intermediates produced through the self-oxidation of DA reduces the dependence on external oxidants in the synthesis of composite materials and predigests the preparation procedure, which provides a novel, simple, and green strategy for the synthesis of other newly catechol-based functional copolymers.

A multifunctional switching bidirectional optical absorber based on a titanium nitride metamaterial.

In this paper, a novel type of tunable ultra-wide band and double-narrow band artificial electromagnetic absorption device is studied. This work uses a titanium nitride-titanium-tungsten (TiN-Ti-W) composite ring array, a TiN reflector layer, and a silver-titanium dioxide-silver (Ag-TiO2-Ag) three layer composite structure to prepare the absorption layer. The simulation results illustrate that the absorption rate can reach 96.6% when the absorption wavelength is 300-2800 nm. When the light source is backward incidence, ultra-narrow band absorption can occur at specific wavelengths of 465 nm and 932 nm. This proves that the absorber is in good agreement with the impedance matching theory. The research results of this work will provide a theoretical basis for the design and application of solar thermal energy conversion.

Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis.

OBJECTIVE: Fibroblast-like synoviocytes (FLSs) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLSs in relapse and remission of RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease-modifying antirheumatic drugs. METHODS: Combining single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three patients with relapse RA and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using quantitative real-time PCR (qPCR) and multiplex immunohistochemistry (mIHC). We further targeted the critical signals in vitro and in vivo using the collagen-induced arthritis (CIA) model in rats. RESULTS: Lining and sublining FLS subsets were identified using scRNA-seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLSs from patients with relapse RA for which mIHC confirmed the increased expression of FGF10. Although the type I interferon pathway was also activated in the lining FLSs, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by small interfering RNA in FLSs significantly reduced the expression of receptor activator of NF-κB ligand. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human-derived pannus cell culture, whereas the FGF receptor (FGFR) 1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model. CONCLUSION: The FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue-specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA.

A noncovalent backbone planarization strategy increases the NIR-II extinction coefficients for gas/phototheranostic applications.

We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.

Chemical synthesis of a 28 kDa full-length PET degrading enzyme ICCG by the removable backbone modification strategy.

Chemical protein synthesis offers a powerful way to access otherwise-difficult-to-obtain proteins such as mirror-image proteins. Although a large number of proteins have been chemically synthesized to date, the acquisition to proteins containing hydrophobic peptide fragments has proven challenging. Here, we describe an approach that combines the removable backbone modification strategy and the peptide hydrazide-based native chemical ligation for the chemical synthesis of a 28 kDa full-length PET degrading enzyme IGGC (a higher depolymerization efficiency of variant leaf-branch compost cutinase (LCC)) containing hydrophobic peptide segments. The synthetic ICCG exhibits the enzymatic activity and will be useful in establishing the corresponding mirror-image version of ICCG.

A Mitochondria-Targeted NIR-II Molecule Fluorophore for Precise Cancer Phototheranostics.

Subcellular organelle mitochondria are becoming a key player and a driver of cancer. Mitochondrial targeting phototheranostics has attracted increasing attention for precise cancer therapy. However, those phototheranostic systems still face great challenges, including complex and multiple components, light scattering, and insufficient therapeutic efficacy. Herein, a molecular fluorophore IR-TPP-1100 was tactfully designed by molecular engineering for mitochondria-targeted fluorescence imaging-guided phototherapy in the second near-infrared window (NIR-II). IR-TPP-1100 not only exhibited prominent photophysical properties and high photothermal conversion efficiency but also achieved excellent mitochondria-targeting ability. The mitochondria-targeting IR-TPP-1100 enabled NIR-II fluorescence and photoacoustic dual-modality imaging of mitochondria at the organism level. Moreover, it integrated photothermal and photodynamic therapy, obtaining remarkable tumor therapeutic efficacy by inducing mitochondrial apoptosis. These results indicate that IR-TPP-1100 has great potential for precise cancer therapy and provides a promising strategy for developing mitochondria-targeting NIR-II phototheranostic agents.

Functional polymer brushes for anti-microplastic pollution.

Image 1.

Near infrared II excitation nanoplatform for photothermal/chemodynamic/antibiotic synergistic therapy combating bacterial biofilm infections.

Drug-resistant bacterial biofilm infections (BBIs) are refractory to elimination. Near-infrared-II photothermal therapy (NIR-II PTT) and chemodynamic therapy (CDT) are emerging antibiofilm approaches because of the heavy damage they inflict upon bacterial membrane structures and minimal drug-resistance. Hence, synergistic NIR-II PTT and CDT hold great promise for enhancing the therapeutic efficacy of BBIs. Herein, we propose a biofilm microenvironment (BME)-responsive nanoplatform, BTFB@Fe@Van, for use in the synergistic NIR-II PTT/CDT/antibiotic treatment of BBIs. BTFB@Fe@Van was prepared through the self-assembly of phenylboronic acid (PBA)-modified small-molecule BTFB, vancomycin, and the CDT catalyst Fe2+ ions in DSPE-PEG2000. Vancomycin was conjugated with BTFB through a pH-sensitive PBA-diol interaction, while the Fe2+ ions were bonded to the sulfur and nitrogen atoms of BTFB. The PBA-diol bonds decomposed in the acidic BME, simultaneously freeing the vancomycin and Fe2+ irons. Subsequently, the catalytic product hydroxyl radical was generated by the Fe2+ ions in the oxidative BME overexpressed with H2O2. Moreover, under 1064 nm laser, BTFB@Fe@Van exhibited outstanding hyperthermia and accelerated the release rate of vancomycin and the efficacy of CDT. Furthermore, the BTFB@Fe@Van nanoplatform enabled the precise NIR-II imaging of the infected sites. Both in-vitro and in-vivo experiments demonstrated that BTFB@Fe@Van possesses a synergistic NIR-II PTT/CDT/antibiotic mechanism against BBIs.

Learnable axonal delay in spiking neural networks improves spoken word recognition.

Spiking neural networks (SNNs), which are composed of biologically plausible spiking neurons, and combined with bio-physically realistic auditory periphery models, offer a means to explore and understand human auditory processing-especially in tasks where precise timing is essential. However, because of the inherent temporal complexity in spike sequences, the performance of SNNs has remained less competitive compared to artificial neural networks (ANNs). To tackle this challenge, a fundamental research topic is the configuration of spike-timing and the exploration of more intricate architectures. In this work, we demonstrate a learnable axonal delay combined with local skip-connections yields state-of-the-art performance on challenging benchmarks for spoken word recognition. Additionally, we introduce an auxiliary loss term to further enhance accuracy and stability. Experiments on the neuromorphic speech benchmark datasets, NTIDIDIGITS and SHD, show improvements in performance when incorporating our delay module in comparison to vanilla feedforward SNNs. Specifically, with the integration of our delay module, the performance on NTIDIDIGITS and SHD improves by 14% and 18%, respectively. When paired with local skip-connections and the auxiliary loss, our approach surpasses both recurrent and convolutional neural networks, yet uses 10 × fewer parameters for NTIDIDIGITS and 7 × fewer for SHD.

Convergent application of traditional Chinese medicine and gut microbiota in ameliorate of cirrhosis: a data mining and Mendelian randomization study.

Objective: Traditional Chinese medicine (TCM) has been used for the treatment of chronic liver diseases for a long time, with proven safety and efficacy in clinical settings. Previous studies suggest that the therapeutic mechanism of TCM for hepatitis B cirrhosis may involve the gut microbiota. Nevertheless, the causal relationship between the gut microbiota, which is closely linked to TCM, and cirrhosis remains unknown. This study aims to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship between gut microbes and cirrhosis, as well as to elucidate the synergistic mechanisms between botanical drugs and microbiota in treating cirrhosis. Methods: Eight databases were systematically searched through May 2022 to identify clinical studies on TCM for hepatitis B cirrhosis. We analyzed the frequency, properties, flavors, and meridians of Chinese medicinals based on TCM theories and utilized the Apriori algorithm to identify the core botanical drugs for cirrhosis treatment. Cross-database comparison elucidated gut microbes sharing therapeutic targets with these core botanical drugs. MR analysis assessed consistency between gut microbiota causally implicated in cirrhosis and microbiota sharing therapeutic targets with key botanicals. Results: Our findings revealed differences between the Chinese medicinals used for compensated and decompensated cirrhosis, with distinct frequency, dosage, properties, flavors, and meridian based on TCM theory. Angelicae Sinensis Radix, Salviae Miltiorrhizae Radix Et Rhizoma, Poria, Paeoniae Radix Alba, Astragali Radix, Atrctylodis Macrocephalae Rhizoma were the main botanicals. Botanical drugs and gut microbiota target MAPK1, VEGFA, STAT3, AKT1, RELA, JUN, and ESR1 in the treatment of hepatitis B cirrhosis, and their combined use has shown promise for cirrhosis treatment. MR analysis demonstrated a positive correlation between increased ClostridialesvadinBB60 and Ruminococcustorques abundance and heightened cirrhosis risk. In contrast, Eubacteriumruminantium, Lachnospiraceae, Eubacteriumnodatum, RuminococcaceaeNK4A214, Veillonella, and RuminococcaceaeUCG002 associated with reduced cirrhosis risk. Notably, Lachnospiraceae shares key therapeutic targets with core botanicals, which can treat cirrhosis at a causal level. Conclusion: We identified 6 core botanical drugs for managing compensated and decompensated hepatitis B cirrhosis, despite slight prescription differences. The core botanical drugs affected cirrhosis through multiple targets and pathways. The shared biological effects between botanicals and protective gut microbiota offer a potential explanation for the therapeutic benefits of these key herbal components in treating cirrhosis. Elucidating these mechanisms provides crucial insights to inform new drug development and optimize clinical therapy for hepatitis B cirrhosis.