Integrating network analysis and pharmacokinetics to investigate the mechanisms of Danzhi Tiaozhi Decoction in metabolic-associated fatty liver disease (MAFLD).

ETHNOPHARMACOLOGICAL RELEVANCE: Based on ancient classics, Danzhi Tiaozhi Decoction has been successfully used to treat nonalcoholic fatty liver disease for decades. However, its therapeutic mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate the effects of Danzhi Tiaozhi Decoction (DZTZD) on metabolic-associated fatty liver disease (MAFLD). MATERIALS AND METHODS: First, we identified the active ingredients of DZTZD and their potential targets in the Traditional Chinese Medicine System Pharmacology database. Using the overlapped genes, we selected the key MAFLD-associated genes, then conducted GO and KEGG pathway enrichment analyses. Furthermore, DZTZD was administered orally to rats, and their serum and liver tissues were examined for absorbed compounds using pharmacochemistry. UPLC-Q-Exactive Orbitrap/MS was used to determine the main compounds. Then, we validated the binding association of the key targets with their active compounds with AutoDock Tools and other software. Finally, the predicted hub targets were experimentally validated. RESULTS: We found 254 active compounds in DZTZD corresponding to 208 targets. Sixteen key genes were identified, and the enrichment analysis revealed multiple signaling pathways, including the AGE-RAGE pathway in diabetic complications and the lipid and atherosclerosis signaling pathway. Next, 160 absorbed components and metabolites were characterized in vivo, and 53 absorbed components and metabolites were characterized in liver tissue. Thirteen parent compounds were identified, including coptisine, quercetin, luteolin, and aloe-emodin. The molecular docking data demonstrated the strongest binding between the active compounds and the core proteins. Moreover, the animal experiments showed that DZTZD decreased body weight, liver weight, lipid accumulation, and ALT, AST, CRP, FFA, IL-6, PEPCK, G6P, TG, TC, and LDL-c serum levels, and increased serum HDL-c levels compared to high-fat induced rats. Besides, the RT-PCR and Western blot showed that DZTZD inhibited the SREBP1c and FAS and increased hyperlipidemia-induced CPT-1A levels. In the high-fat group, JNK phosphorylation increased, and AKT protein phosphorylation decreased, while DZTZD reversed these effects. CONCLUSION: Based on the pharmacological network analysis, pharmacochemistry, and experimental validation, DZTZD can potentially improve MAFLD via the JNK/AKT pathway.

Identification and Thermostability Modification of the Mesophilic L-asparaginase from Limosilactobacillus secaliphilus.

L-asparaginase (L-ASNase, E.C.3.5.1.1) could effectively inhibit the formation of acrylamide (AA) by hydrolyzing the AA precursor L-asparagine. However, most of the L-ASNases showed a relatively weak thermostability, posing a big threat on the application of enzyme at high processing temperatures. Here, the recombinant L-ASNase from mesophilic bacteria Limosilactobacillus secaliphilus was identified for the first time. The recombinant enzyme exhibited its optimal activity at pH 8.0 and 60 ℃. Additionally, the thermostability of L. secaliphilus L-ASNase was enhanced by site-directed mutagenesis after multiple sequence alignment. Ten mutants were reasonably constructed, among which the single-point mutants L24Y, S55T, and V155S showed more than 1 ℃ elevated Tm value compared to the wild-type enzyme. In addition, the half-life of mutant at 40, 50, and 55 ℃ was 376.7 min, 62.1 min, and 18.7 min, much higher than that of wild-type enzyme. The molecular dynamic simulation showed that compared to the wild-type enzyme, the structural stability of V155S was greatly strengthened due to the lower RMSF and RMSD value as well as a decreased total energy compared to that of the wild-type enzyme. The results were positive and provided some useful information for the thermostability modification of L-ASNase.

Regulatory Effects and Mechanisms of L-Theanine on Neurotransmitters via Liver-Brain Axis Under a High Protein Diet.

Excessive protein intake causes liver and brain damage and neurotransmitter disorders, thereby inducing cognitive dysfunction. L-theanine can regulate the neurotransmitter content and show great potential in liver and brain protection. However, it remains unclear whether l-theanine effectively regulates neurotransmitter content under high-protein diet. A 40-day feeding experiment was performed in Sprague Dawley rats to investigate the regulatory effects and mechanisms of l-theanine on neurotransmitters via liver-brain axis in high-protein diets. The results showed that a 30% protein diet increased the liver and brain neurotransmitter content while maintaining the normal structure of liver and the hippocampal CA1 of brain and improving the autonomous behavior of rats. In contrast, 40% and 50% protein diets decreased the content of neurotransmitters, affected autonomous behavior, destroyed the hippocampal CA1 of brain structure, increased hepatic inflammatory infiltration, lipid degeneration, and hepatocyte eosinophilic change in liver, increased liver AST, ALT, MDA, CRP, and blood ammonia level, and decreased liver SOD and CAT level. However, l-theanine improved liver and brain neurotransmitter content, autonomous behavior, liver and hippocampal brain structure, and liver biochemical indicators in 40% and 50% protein diets. To explore how LTA can eliminate the adverse effects of a high-protein diet, we analyzed different metabolites and proteomes and using western blotting for validate quantitatively. We found that l-theanine regulates the activity of PF4 and G protein subunit alpha i2, increases the content of brain-derived neurotrophic factor and dopamine under a 20% protein diet. In addition, l-theanine can activate the adenylate cyclase-protein kinase A pathway through the protein alpha/beta-hydrolase domain protein 12 to regulate the content of neurotransmitters under a 40% protein diet, thereby exerting a neuroprotective effect.

Bacterial distinctions in practical rural sewage collection systems caused by the location, season, and system type.

Bacteria in rural sewage collection systems have the important influences on operation and maintenance risks, such as sedimentation blockage and harmful gas accumulation, and pollutant pre-treatment ability. It is necessary to analyze and interpret the influence on bacterial communities caused by the location (sewage, biofilms, and deposits), season (winter and spring, summer and autumn), and system type (sewers and ditches) to better understand the bacterial characteristics in rural sewage collection systems. To achieve the above purpose, 96 samples obtained from practical rural sewage collection systems in eight villages were analyzed by 16S rRNA whole region sequencing methods. The results indicate that locations and seasons caused significant influences on the overall bacterial communities, which were mainly affected by temperature, sewage quality and bacterial survival preference, and 13 genera of sulfate-reducing bacteria (SRB), 2 genera of ammonia-oxidizing bacteria (AOB), 2 genera of nitrite-oxidizing bacteria (NOB), and 9 genera of water-related pathogenic bacteria (WPB) were detected in rural sewage collection systems. SRB, AOB, NOB, and WPB tended to inhabit in biofilms or deposits rather than in sewage. The total relative abundance of SRB in summer and autumn (∼2.19%) was higher than in winter and spring (∼0.41%), and the WPB distribution in different seasons showed significant distinction. Additionally, some of SRB, AOB, NOB, and WPB also showed significant differences in sewers and ditches. Overall, this study provided a deeper understanding of bacteria in rural sewage collection systems and could further provide the basic parameter for the operation and maintenance risk control.

Investigation on sleep quality and psychological distress in patients with pulmonary nodules.

BACKGROUND: Patients with pulmonary nodules (PNs) often suffer from the psychological burden of their disease and trap in sleep problems. This is insufficiently identified and addressed in clinical practice. The aim of this study was to investigate the psychological distress and sleep quality among PN patients and identify potential risk or protective factors for sleep quality. METHODS: We conducted a cross-sectional study, which included 731 PN patients who visited the thoracic clinic of Guangdong Provincial People's Hospital. Each participant completed a structured questionnaire consisting of demographic characteristics, clinical characteristics, the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). The reliability of the HADS (Cronbach's α = 0.944) and PSQI (Cronbach's α = 0. 0.757) in this study was satisfactory. RESULTS: A total of 328 patients (44.9%) had PSQI global scores > 5, indicating poor quality of sleep. Age ≥ 50 years (OR 1.88, 95% CI 1.35-2.58; P < 0.001), female (OR 1.56, 95% CI 1.05-2.33; P = 0.028), detection of nodule for 7-12 months (vs for more than 24 months, OR 2.14, 95%CI 1.18-3.89, P = 0.013), anxiety (OR 1.78, 95% CI 1.17-2.71; P = 0.007) and depression (OR 1.84, 95% CI 1.16-2.92; P = 0.010) were independent risk factors for impaired sleep quality. A significant correlation revealed that sleep quality was positively correlated with both anxiety and depression (Spearman r = 0.342, P < 0.001 and Spearman r = 0.314, P < 0.001, respectively). All dimensions of the PSQI scale were significantly decreased in both anxiety group and depression group compared to the psychologically normal group (P < 0.05). CONCLUSIONS: Impaired sleep quality is highly prevalent among patients with PNs and associated with age, gender, time from the date of detection, anxiety and depression. Based on the finding of impaired sleep quality and psychological health, screening for psychological and sleep problems in PN patients will be of great clinical benefit.

An enhanced activity and thermostability of chimeric Bst DNA polymerase for isothermal amplification applications.

Loop-mediated isothermal amplification (LAMP) is a widely used method for clinical diagnosis, customs quarantine, and disease prevention. However, the low catalytic activity of Bst DNA polymerase has made it challenging to develop rapid and reliable point-of-care testing. Herein, we developed a series of Bst DNA polymerase mutants with enhanced activity by predicting and analyzing the activity sites. Among these mutants, single mutants K431D and K431E showed a 1.93- and 2.03-fold increase in catalytic efficiency, respectively. We also created a chimeric protein by fusing the DNA-binding domain of DNA ligase from Pyrococcus abyssi (DBD), namely DBD-K431E, which enabled real-time LAMP at high temperatures up to 73 ℃ and remained active after heating at 70 ℃ for 8 h. The chimeric DBD-K431E remained active in the presence of 50 U/mL heparin, 10% ethanol, and up to 100 mM NaCl, and showed higher activity in 110 mM (NH4)2SO4, 110 mM KCl, and 12 mM MgSO4. Notably, it generated a fluorescence signal during the detection of Salmonella typhimurium at 2 × 102 ag/µL of genomic DNA and 1.24 CFU/mL of bacterial colony, outperforming the wild type and the commercial counterpart Bst 2.0. Our results suggest that the DBD-K431E variant could be a promising tool for general molecular biology research and clinical diagnostics. KEY POINTS: • Residue K431 is probably a key site of Bst DNA polymerase activity • The chimeric DBD-K431E is more inhibitor tolerant and thermostable than Bst-LF • The DBD-K431E variant can detect Salmonella typhimurium at 102 ag/µL or 100 CFU/mL.

Establishment and bioinformatics evaluation of the ethanol combined with palmitic acid-induced mouse hepatocyte AFLD model (the Hu-Qiu Model).

Chronic alcoholic liver disease has brought great harm to human health. Alcoholic fatty liver disease is the first stage in the progression of all chronic alcoholic liver diseases. At present, there is no cell model that fully matches the etiology (high-fat diet + alcohol) of human alcoholic fatty liver disease. We used 100 mM ethanol +6.25 µM PA to establish the ethanol combined with PA-induced mouse hepatocyte AFLD model (EP-AFLD hepatocyte model) and performed the RNA-seq transcriptome sequencing. Through bioinformatics analysis and comparison, we discovered that the EP-AFLD hepatocyte model was more suitable for studying the pathological mechanism of AFLD than the mouse AFLD hepatocyte model induced by ethanol alone. And through bioinformatics analysis, we further discovered that 77 genes from the differential expression gene set of EP-AFLD hepatocyte model were engaged in the pathological process of mouse AFLD and 40 genes were involved in the pathogenesis of both mouse AFLD and human AFLD. In this study, a novel mouse hepatocyte AFLD model was successfully established by combining ethanol and PA, which can be used to study the molecular mechanism of the pathogenesis of AFLD in mice or humans. This study will provide a brand-new in vitro experimental platform for the in-depth study of AFLD pathogenesis and the screening of AFLD therapeutic drugs.

Association between Nighttime Heart Rate and Cardiovascular Mortality in Patients with Implantable Cardioverter Defibrillator: A Cohort Study.

BACKGROUND: Although studies have shown that an increased resting heart rate measured randomly at a single point of the day has been associated with adverse cardiovascular outcomes, the utility of continuous monitoring of nighttime heart rate (NTHR) has remained largely uninvestigated. OBJECTIVE: This study aimed to explore the association between NTHR and cardiovascular mortality. METHODS: The SUMMIT prospective cohort study enrolled patients with ICD or CRT-D between 2010 and 2015. Baseline NTHR was measured during the programmed sleep period from 30 to 60 days after implantation. The primary outcome was cardiovascular mortality, fitted by a restricted cubic spline function. RESULTS: A total of 534 ICD recipients with sinus rhythm during the detection window were included in the study. The mean baseline NTHR was 59.6 ± 8.0 bpm. During the 60.4 ± 21.8 months follow-up period, 88 patients experienced cardiovascular mortality. After considering potential confounders, a linear association was observed. Each 1 bpm increase in NTHR was associated with a 7.8%, 10.1%, and 5.7% increase in the risk of cardiovascular mortality in the total population, and patients with or without heart failure, respectively. CONCLUSION: Continuous monitoring of NTHR may identify patients at high risk of cardiovascular mortality in a timely manner, with the potential for "pre-emptive" action.

Difficult Blood Typing Caused by Rouleaux Agglutination in Patient with Acute Brain Trauma: a Case Report.

BACKGROUND: Rouleaux agglutination is a common cause of difficult blood typing, but it is rarely reported in patients with acute brain trauma. METHODS: This article describes a 69-year-old male with head injury who was admitted to the hospital. Blood typing showed type O, Rh(D) positive, but the Rh(D) control was also positive. After ruling out the possibility of the patient having abnormal autoantibodies, it was suspected that rouleaux agglutination might be the cause. Microscopic examination of the specimen revealed rouleaux agglutination, which was believed to be the cause of the false-positive Rh(D) control result. The patient's red blood cells were treated with physiological saline and retested by microcolumn gel card testing. RESULTS: The retest showed negative Rh(D) control results, indicating normal results. The patient subsequently received normal blood transfusion. CONCLUSIONS: Laboratory personnel should be aware of the possibility of difficult blood typing caused by rouleaux agglutination in various diseases, especially in relatively rare traumatic diseases.

Development of Potent and Selective Coactivator-Associated Arginine Methyltransferase 1 (CARM1) Degraders.

CARM1 is amplified or overexpressed in many cancer types, and its overexpression correlates with poor prognosis. Potent small-molecule inhibitors for CARM1 have been developed, but the cellular efficacy of the CARM1 inhibitors is limited. We herein report the development of the proteolysis targeting chimera (PROTAC) for CARM1, which contains a CARM1 ligand TP-064, a linker, and a VHL E3 ligase ligand. Compound 3b elicited potent cellular degradation activity (DC50 = 8 nM and Dmax > 95%) in a few hours. Compound 3b degraded CARM1 in VHL- and proteasome-dependent manner and was highly selective for CARM1 over other protein arginine methyltransferases. CARM1 degradation by 3b resulted in potent downregulation of CARM1 substrate methylation and inhibition of cancer cell migration in cell-based assays. Thus, CARM1 PROTACs can be used to interrogate CARM1's cellular functions and potentially be developed as therapeutic agents for targeting CARM1-driven cancers.

Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis.

BACKGROUND: We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second-line versus later-line. Here, we present an updated pooled analysis with a longer follow-up of 35.2 months. METHODS: Data were pooled from two studies-BGB-3111-AU-003 (NCT02343120) and BGB-3111-206 (NCT03206970) of zanubrutinib in R/R MCL. The patients were divided into two groups based on the treatment line of zanubrutinib: the second-line and the later-line group. The inverse propensity score weighting method was used to balance the baseline covariates between the groups. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), PFS, and OS rates, objective response rate (ORR), duration of response (DOR), and safety. RESULTS: Among 112 pooled patients, 41 (36.6%) patients received zanubrutinib as second-line and 71 (63.4%) patients as later-line therapy. After weighting, OS was significantly improved in the second-line versus later-line group (HR, 0.459 [95% CI: 0.215, 0.98]; p = 0.044) with median OS not estimable in both groups. The PFS was similar between the two groups (HR, 0.78 [95% CI: 0.443, 1.373]; p = 0.389) but with numerically longer median PFS in the second-line versus later-line group (27.8 vs. 22.1 months). ORR was numerically higher in the second-line versus later-line (88.6% vs. 85.7%), and DOR was similar between the two groups (25.2 vs. 25.1 months). Zanubrutinib showed a similar safety profile in both groups. CONCLUSION: Zanubrutinib in second-line treatment was associated with significantly improved OS compared with later-line treatment of R/R MCL.

Rational Design of Sulfonyl-γ-AApeptides as Highly Potent HIV-1 Fusion Inhibitors with Broad-Spectrum Activity.

The HIV-1 epidemic has significant social and economic implications for public health. Developing new antivirus drugs to eradicate drug resistance is still urgently needed. Herein, we demonstrated that sulfonyl-γ-AApeptides could be designed to mimic MTSC22EK, one potent HIV fusion inhibitor derived from CHR. The best two sequences revealed comparable activity to MTSC22EK in an authentic HIV-1 infection assay and exhibited broad-spectrum anti-HIV-1 activity to many HIV-1 clinical isolates. Furthermore, sulfonyl-γ-AApeptides show remarkable resistance to proteolysis and favorable permeability in PAMPA-GIT and PAMPA-BBB assays, suggesting that both sequences could control HIV-1 within the central nervous system and possess promising oral bioavailability. Mechanistic investigations suggest that these sulfonyl-γ-AApeptides function by mimicking the CHR of gp41 and tightly bind with NHR, thereby inhibiting the formation of the 6-HB structure necessary for HIV-1 fusion. Overall, our results suggest that sulfonyl-γ-AApeptides represent a new generation of anti-HIV-1 fusion inhibitors. Moreover, this design strategy could be adopted to modulate many of the PPIs.

Four-band terahertz metamaterial absorber based on Dirac semimetal for a refractive index sensing application.

We design a four-band narrow-band near-perfect absorber based on bulk Dirac semimetal (BDS) metamaterial in the terahertz region. The absorber has a top-to-bottom three-layer structure of a BDS layer, an insulating dielectric slab, and a gold layer. The BDS is flexible and tunable, allowing the Fermi energy level to be adjusted by changing the applied bias voltage, thus changing the absorption characteristics of the absorber. We use the time-domain finite-difference method to simulate the absorption characteristics of the absorber, which could achieve four discrete near-perfect absorption peaks at 0.98 THz, 1.70 THz, 2.02 THz, and 2.36 THz. The absorber is polarization sensitive, and the conversion between four-band absorption and three-band absorption is achieved by changing the incident polarization angle. We also change the structure of the absorber to study the absorption characteristics and break the structural symmetry to achieve a larger number of absorption peaks. Besides, the sensing performance of four-band narrow-band absorption is analyzed, and the maximum sensitivity of the absorber is 112.78 GHz/RIU. The device should have vast application prospects for bio-detection and high-sensitivity biosensing detection.

Investigating the antidepressant effect of Ziyan green tea on chronic unpredictable mild stress mice through fecal metabolomics.

Introduction: Some studies have shown the effectiveness of tea in reducing depression. Gut flora dysfunction is strongly associated with depression. The mechanism by which Ziyan green tea ameliorates depression is not clear. Methods: In this study, we examined the impact of Ziyan green tea on mice exhibiting symptoms similar to depression. We specifically focused on the role of intestinal flora and its metabolites. We first established a chronic unpredictable mild stress (CUMS) mouse model to induce depressive symptoms and conducted behavioural tests, biochemical tests, and pathological tissue analysis. We also investigated gut microbiota changes by 16S rRNA sequencing and measured faecal metabolites in mice using UHPLC-MS/MS. Results: The results showed that Ziyan green tea intervention improved depression-like behaviour, neurobiochemical factors, and reduced levels of pro-inflammatory factors in CUMS mice. Spearman's correlation analysis showed that different microbial communities (Corynebacterium, Faecalibaculum, Enterorhabdus, Desulfovibrio) correlation with differential metabolites (Cholic acid, Deoxycholic acid, etc.) and depression-related biochemical indicators (5-HT, DA, BDNF, IL-6, and TNF-α). Discussion: In conclusion, our findings suggest that both low and high-dose interventions of Ziyan green tea have positive preventive effects on CUMS mice without dose dependence, partly because they mainly affect intestinal Purine Metabolism, Bile Acid Biosynthesis and Cysteine Metabolism in CUMS mice, thus stimulating brain 5-HT, DA and BDNF, and decreasing the inflammatory factors IL-6, TNF-α, activate the composition of intestinal flora, improve the intestinal flora environment and thus promote the production of intestinal metabolites, which can be used for depression treatment. It is suggested that Ziyan green tea may achieve an antidepressant effect through the gut-microbiota-brain axis.

The prognostic value of cancer stage-associated genes in clear cell renal cell carcinoma.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is a highly prevalent subtype of malignant renal tumor, but unfortunately, the survival rate remains unsatisfactory. The aim of the present study is to explore genomic features that are correlated with cancer stage, allowing for the identification of subgroups of ccRCC patients with high risk of unfavorable outcomes and enabling prompt intervention and treatment. METHODS: We compared the gene expression levels across ccRCC patients with diverse cancer stages from The Cancer Genome Atlas (TCGA) database, which revealed characteristic genes associated with tumor stage. We then extracted prognostic genes and used least absolute shrinkage selection operator (LASSO) regression to select four genes for feature extraction and the construction of a prognostic risk model. RESULTS: We have identified a total of 171 differentially expressed genes (DEGs) that are closely linked to the tumor stage of ccRCC through difference analysis. A prognostic risk model constructed based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 holds significant prognostic value in ccRCC. The results of the functional enrichment analysis imply that the DEGs are mainly involved in the regulation of immune-related signaling pathways, and therefore may have a significant function in immune system regulation of ccRCC. CONCLUSIONS: Our study has successfully identified significant DEGs between high- and low-staging groups of ccRCC using bioinformatics methods. The construction of a prognostic risk model based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 has displayed promising prognostic significance, indicating its valuable potential for clinical application.

A rapid review on the COVID-19's global impact on breast cancer screening participation rates and volumes from January-December 2020.

COVID-19 has strained population breast mammography screening programs that aim to diagnose and treat breast cancers earlier. As the pandemic has affected countries differently, we aimed to quantify changes in breast screening volume and uptake during the first year of COVID-19 crisis. We systematically searched Medline, the WHO (World Health Organization) COVID-19 database, and governmental databases. Studies covering January 2020 to March 2022 were included. We extracted and analyzed data regarding study methodology, screening volume and uptake. To assess for risk-of-bias, we used the Joanna Briggs Institute Critical Appraisal tool. Twenty-six cross-sectional descriptive studies (focusing on 13 countries) were included out of 935 independent records. Reductions in screening volume and uptake rates were observed among eight countries. Changes in screening participation volume in five countries with national population-based screening ranged from -13% to -31%. Among two countries with limited population-based programs the decline ranged from -61% to -41%. Within the USA, population participation volumes varied ranging from +18% to -39% with suggestion of differences by insurance status (HMO, Medicare, and low-income programs). Almost all studies had high risk-of-bias due to insufficient statistical analysis and confounding factors. Extent of COVID-19-induced reduction in breast screening participation volume differed by region and data suggested potential differences by healthcare setting (e.g., national health insurance vs private health care). Recovery efforts should monitor access to screening and early diagnosis to determine if prevention services need strengthening to increase coverage of disadvantaged groups and reduce disparities.

Enhancing Prediction for Tumor Pathologic Response to Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Cancer by Dynamic Parameters from Clinical Assessments.

To develop accurate and accessible prediction methods for assessing pathologic response following NICT prior to surgery, we conducted a retrospective study including 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after two cycles of NICT between January 2019 and March 2022 at our center. We collected clinical parameters to evaluate the dynamic changes in the primary tumor. Univariate and multivariate analyses were performed to determine the correlations between these parameters and the pathologic response of the primary tumor. Subsequently, we constructed prediction models for pCR and MPR using multivariate logistic regression. The MPR prediction Model 2 was internally validated using bootstrapping and externally validated using an independent cohort from our center. The univariate logistic analysis revealed significant differences in clinical parameters reflecting tumor regression among patients with varying pathologic responses. The clinical models based on these assessments demonstrated excellent predictive performance, with the training cohort achieving a C-index of 0.879 for pCR and 0.912 for MPR, while the testing cohort also achieved a C-index of 0.912 for MPR. Notably, the MPR prediction Model 2, with a threshold cut-off of 0.74, exhibited 92.7% specificity and greater than 70% sensitivity, indicating a low rate of underestimating residual tumors. In conclusion, our study demonstrated the high accuracy of clinical assessment-based models in pathologic response prediction, aiding in decision-making regarding organ preservation and radiotherapy adjustments after induction immunochemotherapy.