Chronic pancreatitis （CP） is a common disease in clinical practice characterized by progressive inflammatory fibrosis of the pancreas. Gut microbiota， known as the “second genome” of humans， bidirectionally modulates the progression of fibrosis in CP via the gut-pancreas axis. This article systematically elaborates on the characteristics of gut microbiota during the progression of CP and its molecular mechanism in mediating pancreatic fibrosis through bacterial translocation， metabolites， immune regulatory networks， and microbe-pancreatic stellate cell interactions， with a focus on the pivotal role of short-chain fatty acids and inflammatory cytokine networks in pancreatic stellate cell activation and extracellular matrix deposition. In addition， this article explores the potential value of gut microbiota-targeted interventions in the prevention and treatment of CP fibrosis， such as probiotics， prebiotics， and fecal microbiota transplantation， and discusses the translational potential of using multi-omics technologies to identify diagnostic biomarkers and novel therapeutic targets for CP， in order to provide new ideas for the precise diagnosis and treatment of CP.

ObjectiveTo develop a machine learning (ML)-based prediction model for neurological rehabilitation outcomes of stroke patients. MethodsA total of 420 stroke patients admitted to the Fuzhou First People's Hospital from October, 2022 to October, 2024 were enrolled as the training set. According to the modified Rankin Scale (mRS) scores three months after discharge, the patients were divided into prognosis group (n = 289) and poor prognosis group (n = 131). An additional 180 stroke patients hospitalized in the same hospital from November, 2024 to April, 2025 were selected as the validation set. Univariate analysis, least absolute shrinkage and selection operator regression, and multivariate logistic regression were performed to identify independent influencing factors for the prognosis of neurological function recovery. Using the screened independent influencing factors as feature variables, six ML models were established, including logistic regression, linear discriminant analysis, naive Bayes, support vector machine, random forest and extreme gradient boosting (XGBoost). The area under the receiver operating characteristic curve (AUC), confusion matrix indicators (accuracy, precision, recall and F1-score), calibration curve and decision curve analysis were adopted to evaluate the predictive efficacy, calibration degree and clinical net benefit of each model, with external validation conducted in the validation set. The SHapley Additive exPlanations framework was used to interpret the optimal model, and bar charts were applied to visualize the feature importance of the best model. ResultsAge, National Institutes of Health Stroke Scale (NIHSS) score, collateral circulation grading, fasting plasma glucose (FPG), lymphocyte percentage (LYMPH%), and homocysteine (Hcy) were independent risk factors for poor neurological rehabilitation prognosis (P < 0.05). For the XGBoost model, the AUC of the training and validation sets were 0.963 (95%CI 0.947 to 0.979) and 0.825 (95%CI 0.764 to 0.885), respectively, while the accuracy was 88.81% and 77.22%, the precision was 92.86% and 68.42%, the recall was 69.47% and 47.27%, and the F1-score was 79.48% and 55.91%, optimal in both calibration and clinical net benefit. The feature importance ranking for the XGBoost model from high to low was NIHSS score, age, collateral circulation grading, FPG, Hcy and LYMPH%. ConclusionThe interpretable XGBoost ML model exhibits excellent predictive efficacy and favorable clinical applicability in predicting neurological rehabilitation outcomes for stroke patients.

ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

Objective To compare the efficacy and safety of gemcitabine combined with conventional-dose cisplatin(70 mg/m2,day 2)versus split-dose cisplatin(35 mg/m2,days 1 and 8)in neo-adjuvant therapy for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 33 MIBC patients receiving(gemcitabine+cisplatin,GC)-based neoadjuvant chemotherapy in the Department of Urology of Xinhua Hospital,during Jan.2021 and Aug.2024 were retrospectively analyzed,including 18(54.5％)patients treated with a conventional-dose regimen(GC group),and 15(45.5％)patients treated with a split-dose regimen(GCs group).The efficacy endpoints and incidence/severity of adverse reactions were compared between the two groups.Results Baseline characteristics were well-balanced between the two groups(P＞0.05).No significant differences were observed in the complete response rate(CR:33.3％vs.22.2％),objective response rate(ORR:66.7％vs.61.1％),or disease control rate(DCR:80.0％vs.88.9％)between the GCs and GC groups(P＞0.05).The GCs group exhibited a significantly lower incidence of chemotherapy-related renal injury(6.7％vs.38.9％,P＜0.05),while the occurrence of other adverse events was comparable between the two groups.Notably,the GCs group demonstrated significantly attenuated nephrotoxicity,as evidenced by markedly smaller changes in estimated glomerular filtration rate[eGFR:(4.5±4.7)％vs.(18.0±11.8)％]and serum creatinine[SCr:(5.7±5.6)％vs.(20.2±19.5)％]compared to the GC group(P＜0.05).Conclusion Compared with the conventional-dose regimen,the split-dose regimen maintains equivalent clinical efficacy of GC-based neoadjuvant chemotherapy while significantly reducing chemotherapy-related nephrotoxicity,thereby providing MIBC patients with a safer therapeutic option.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective To compare the efficacy and safety of gemcitabine combined with conventional-dose cisplatin(70 mg/m2,day 2)versus split-dose cisplatin(35 mg/m2,days 1 and 8)in neo-adjuvant therapy for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 33 MIBC patients receiving(gemcitabine+cisplatin,GC)-based neoadjuvant chemotherapy in the Department of Urology of Xinhua Hospital,during Jan.2021 and Aug.2024 were retrospectively analyzed,including 18(54.5％)patients treated with a conventional-dose regimen(GC group),and 15(45.5％)patients treated with a split-dose regimen(GCs group).The efficacy endpoints and incidence/severity of adverse reactions were compared between the two groups.Results Baseline characteristics were well-balanced between the two groups(P＞0.05).No significant differences were observed in the complete response rate(CR:33.3％vs.22.2％),objective response rate(ORR:66.7％vs.61.1％),or disease control rate(DCR:80.0％vs.88.9％)between the GCs and GC groups(P＞0.05).The GCs group exhibited a significantly lower incidence of chemotherapy-related renal injury(6.7％vs.38.9％,P＜0.05),while the occurrence of other adverse events was comparable between the two groups.Notably,the GCs group demonstrated significantly attenuated nephrotoxicity,as evidenced by markedly smaller changes in estimated glomerular filtration rate[eGFR:(4.5±4.7)％vs.(18.0±11.8)％]and serum creatinine[SCr:(5.7±5.6)％vs.(20.2±19.5)％]compared to the GC group(P＜0.05).Conclusion Compared with the conventional-dose regimen,the split-dose regimen maintains equivalent clinical efficacy of GC-based neoadjuvant chemotherapy while significantly reducing chemotherapy-related nephrotoxicity,thereby providing MIBC patients with a safer therapeutic option.

Objective To deeply understand the anatomical basis of temporomandibular joint disorders,and explore and master the pathological characteristics of anterior displacement of temporomandibular joint disc through cadaveric dissection and 3D printing technology.Methods By dissecting the temporomandibular joints of 40 head and neck specimens,the bilateral structures of the temporomandibular joints were measured to obtain condyle and articular disc data.3D modeling was carried out using 3ds Max software and printed out a model of temporomandibular joint.The pathological model of the anterior disc displacement with reduction(ADDwR)was simulated by adjusting the opening degree,the position of the articular disk,and the position of the condyle of the model.Results The precise data of the right and left temporomandibular joint discs and condyle were successfully obtained by dissection and measurement.The thickness of the anterior band of left temporomandibular joint discs was(2.02±0.57)mm,the thickness of the middle band was(1.46±0.33)mm,the thickness of the posterior band was(3.00±0.46)mm,the anterior-posterior diameter was(9.60±0.72)mm,and the internal-external diameter was(17.73±0.84)mm.While the thickness of the anterior band of right temporomandibular joint discs was(1.84±0.35)mm,and the thickness of the middle band was(1.43±0.28)mm,the thickness of posterior band was(3.08±0.49)mm,the anterior-posterior diameter was(9.30±0.88)mm,and the internal-external diameter was(17.38±1.10)mm.The internal-external diameter of the left temporomandibular joint condyle was(18.97±0.41)mm,and the anterior-posterior diameter was(8.56±0.43)mm;the internal-external diameter of the right temporomandibular joint condyle was(18.86±0.75)mm,and the anterior-posterior diameter was(8.40±0.30)mm.The standard temporomandibular joint model was printed out by the measured data.The model was utilized to simulate the physiological state of temporomandibular joint under normal conditions,as well as the three pathological states of closed mouth,closed mouth to open mouth,and open mouth in the case of ADDwR.Conclusion The temporomandibular joint model can more intuitively present the changes of anatomical structure in reversible temporoman-dibular joint disorders,which is helpful for understanding and mastering the different classification of this disease.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

ObjectiveBased on the theory of "gut-prostate" axis， this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis（CNP） by detecting the levels of inflammatory factors， and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group， and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling， 32 rats were randomly divided into the model group， Ningmitai capsule group（0.50 g·kg^-1）， Zishen Tongguan formula group（2.00 g·kg^-1）， and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group（PCC-AR group， 2.00 g·kg^-1）， with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage， and the normal and model groups were intragastrically administered with an equal volume of normal saline， once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin（HE） staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of related inflammatory factors in rat serum， and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration， and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats， increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors， with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group， the expression levels of interleukin（IL）-8， hypersensitive C-reactive protein（hs-CRP）， immunoglobulin（Ig）M， secretory IgA （sIgA）， and inducible nitric oxide synthase（iNOS） were sIgnificantly increased in the model group（P<0.01）. Compared with the model group， the expression levels of the above inflammatory factors in all administered groups were significantly reduced（P<0.01）. When compared with the PCC-AR group， the Zishen Tongguan formula group showed a significant decrease in transforming growth factor（TGF）-β₁ expression level（P<0.05） and a significant increase in IgM expression level（P<0.01）. The results of gut microbiota analysis showed that， compared with the PCC-AR group， at the order level， the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales， Acidaminococcales， Rhodospirillales， Clostridiales， and Elusimicrobiales（P<0.01）. And at the genus level， the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides（P<0.01） and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus（P<0.01）. ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria， increase the level of beneficial intestinal bacteria， down-regulate the expression of serum inflammatory factors， and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.