Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective: To evaluate the performance of platelet efficacy score (PEscore) in predicting platelet transfusion efficacy in hematological patients. Methods: A total of 485 patients with hematological diseases, including 298 males (62.09±15.45 years) and 187 females (59.17±16.52 years) who received platelet transfusion from January 1, 2021 to December 31, 2024 were enrolled in this study. Clinical data of the patients such as diagnosis, gender, age, number of platelet transfusion, and platelet antibody data were analyzed to investigate the incidence and influencing factors of platelet transfusion refractoriness in hematological patients at our hospital. ROC curve was used to evaluate the performance of PEscore model in predicting platelet transfusion efficacy. The predictive performance of PEscore model was validated by calculating its sensitivity, specificity, and accuracy in 115 clinical cases. Results: The incidence of platelet transfusion refractoriness in 485 cases was 29.90% (145/485). Significant differences (P<0.05) were observed between the effective and ineffective platelet transfusion groups regarding the following factors: diagnosis: lymphoma [55.32% (26/47) vs 44.68% (21/47)], the number of previous platelet transfusions [≥25: 60.78% (31/51) vs 39.22% (20/51)], platelet antibody screening result [positive: 33.76% (53/157) vs 66.24% (104/157)], and platelet transfusion volume (×10 /L) [>6: 62.71% (74/118) vs 37.29% (44/118)]. The area under the ROC curve of PEscore was 0.876. The cut-off points and corresponding sensitivity and specificity were 19.90.59% and 69.44%, respectively. The results of clinical application showed that the sensitivity, specificity and accuracy of the PEscore model for predicting platelet transfusion were 87.50%, 93.41% and 92.17%, respectively. Conclusion: The incidence of platelet transfusion refractoriness in hematological patients is relatively high. PEscore prediction model has a good performance in predicting the effect of platelet transfusion, which can provide a reliable basis for predicting the effect of platelet transfusion in hematological patients before blood transfusion.

Background Existing studies suggest that cadmium exposure is associated with the occurrence of cardiovascular disease (CVD), but the current epidemiological evidence is inconsistent. Objective To systematically evaluate the relationship between cadmium exposure and CVD through meta-analysis. Methods We systematically searched PubMed, Cochrane Library, Web of Science, CNKI, Wanfang and SinoMed databases to collect observational studies on the relationship between cadmium exposure and CVD in human population published until July 30, 2024. On the basis of following predetermined inclusion and exclusion criteria, the retrieved literature was systematically screened, and the basic information of the included research was extracted, including basic participant information, research outcomes, and data results. This study used the Newcastle-Ottawa Scale and a cross-sectional study evaluation protocol (11 items) recommended by the Quality of Health Care and Research Institutions of the United States for literature quality evaluation. Meta-analysis, subgroup analysis, sensitivity analysis, and assessment of publication bias of the data were conducted using Stata16.0 software. Result A total of 15 studies (18 datasets) were included, and the quality of all the studies was graded as medium or above. Among them, there were 10593 cases of CVD and 86801 controls. The results of meta-analysis showed that the standard mean difference (SMD) of the CVD case group was 0.44 and 95% confidence interval (95%CI) was (0.30, 0.58), and the cadmium exposure level of the CVD case group was higher than that of the control group (P<0.05). The subgroup analysis showed that the cadmium exposure levels in the CVD patients from the Americas (SMD=0.46, 95%CI: 0.29, 0.63) and Europe (SMD=0.14, 95%CI: 0.09, 0.19) were higher than those in the control group (P<0.05). The cadmium levels in blood (SMD=0.52, 95%CI: 0.31, 0.73) and urine (SMD=0.34, 95%CI: 0.16, 0.52) in the CVD case group were higher than those in the control group (P<0.05). In those cross-sectional studies (SMD=0.34, 95%CI: 0.23, 0.46), the cadmium exposure level in the CVD patients was higher than that in the control group (P<0.05). The sensitivity analysis showed robust meta-analysis results and the assessment of publication bias also showed no publication bias. Conclusion Cadmium exposure may increase the risk of cardiovascular disease after multiple studies were combined by meta analysis, suggesting that the scope and level of cadmium exposure in the population should be further controlled.

Non-clinical reproductive toxicity studies typically employ mammals like rats, rabbits, and cynomolgus monkeys, with animal pregnancy being a key challenge in such testing. This article focuses on the difficulties encountered in the animal pregnancy process and potential countermeasures. Rats can be used for fertility and early embryonic development toxicity studies (Segment Ⅰ), embryo-fetal development toxicity studies (Segment Ⅱ), and perinatal toxicity studies (Segment Ⅲ). The estrous cycle of female rats can be determined by vaginal smear, and mating behavior is confirmed through copulatory plug checks the following day after pairing one female with one male in the same cage. Rabbits are commonly used in embryo-fetal development toxicity studies (Segment Ⅱ). Mating behavior between male rabbits and estrous females is observed to determine the time of conception. However, challenges such as atypical estrus of female rabbits, large variations in estrus between batches, and mating failure often occur in reproductive toxicity testing, which may be addressed through prolonged light exposure, increased protein supplementation, optimized mating strategies, and environmental modifications like female and male rabbits are raised adjacent to each other. Non-human primates (NHPs) are typically employed in perinatal toxicity studies (Segment Ⅲ), where one of the key challenges lies in accurately determining sexual maturity in males - a critical factor for reproductive toxicity testing, which can be assessed through comprehensive evaluation of age, body weight, and testicular volume. Generally, male macaques are considered sexually mature when they meet the following criteria: age >4.5 years, body weight >4.5 kg, single testis volume >10 mL, and combined testicular volume >20 mL. For pregnancy confirmation, ultrasound examination demonstrating visible gestational sacs is required, though this necessitates experienced veterinary clinicians to establish standardized ultrasound examination protocols. In conclusion, reproductive toxicity studies should employ species-appropriate detection methods and evaluation criteria based on anatomical characteristics of the reproductive system to ensure successful mating and proper study execution.

OBJECTIVE To explore the efficacy and safety of different doses of bupivacaine liposome （referred to as “LB”） in posterior quadratus lumborum block （QLB） for postoperative analgesia in patients undergoing cesarean section （CS）. METHODS In prospective research method， a total of 168 patients undergoing CS admitted to Chongzhou Maternal and Child Health Hospital from June to December 2024 were randomly divided into LB1 group， LB2 group， and LB3 group （LB of 199， 133 and 67 mg， respectively） according to the random number sorting method， with 56 cases in each group. All patients underwent CS after combined spinal-epidural anesthesia， and received patient-controlled intravenous analgesia and bilateral posterior QLB with different doses of LB after the operation. Visual analogue scale score， Ramsay sedation score， the presence of postoperative block planes and muscle strength classification were observed in the three groups of patients at 6， 12， 24， 48 and 72 hours after the operation. The time of the first compression of the analgesic pump， the dosage of sufentanil and butorphanol within 72 hours after surgery， the number of compressions of the analgesic pump， the analgesic rescue rate， the time of initiating lactation， the score of neonatal behavioral neurological assessment （NBNA）， the time of postoperative exhaust， the indwelling time of urinary catheter， the length of hospital stay， and the total satisfaction at 72 hours after surgery were compared. The occurrence of adverse reactions within 72 hours after the operation was recorded. RESULTS The resting and motor pain scores， the dosage of sufentanil and butorphanol within 72 hours after surgery， the number of compressions of the analgesic pump， the analgesic rescue rate， and the time of initiating lactation at 6， 12， 24， 48 and 72 hours after surgery in the LB1 group and the LB2 group were significantly lower or shorter than those in the LB3 group（P＜0.05）. The proportion of postoperative block planes at 24， 48 and 72 hours after surgery， the time of the first compression of the analgesic pump and the total satisfaction in the LB1 group and the LB2 group were significantly higher or longer than those in the LB3 group（P＜0.05）. The proportion of patients with muscle strength≤grade 3 at 6 hours after surgery in the LB1 group was significantly higher than that in the LB2 and the LB3 groups （P＜0.05）. There were no statistically significant differences in the Ramsay sedation scores at each time point after surgery， NBNA scores， postoperative exhaust time， urinary catheter indwelling time， the length of hospital stay， as well as the occurrence of adverse reactions among the 3 groups （P＞0.05）. CONCLUSIONS Compared with 67 mg of LB， 199 mg and 133 mg of LB can improve the postoperative analgesic effect and total satisfaction of CS patients undergoing posterior QLB， reduce the use of postoperative analgesic drugs， and shorten the time to start lactation. Compared with 199 mg and 133 mg of LB， 67 mg of LB has a smaller impact on the motor function of CS patients. All three doses of LB had no significant effect on the neurobehavioral abilities of newborns, and demonstrated comparable sedative efficacy and safety.

ObjectiveTo compare the protective effects of water extracts from fresh and dried Dendrobium huoshanense on gastric mucosa in chronic atrophic gastritis （CAG）. MethodsMale SD rats （n=72） were randomly divided into 9 groups， with 8 rats in each group， which were normal group， model group， Yangwei Shu （4 g·kg^-1） group， low-， medium-， and high-dose fresh D. huoshanense （3.5， 7， and 14 g·kg^-1） groups， and low-， medium-， and high-dose dried D. huoshanense （0.7， 1.4， 2.8 g·kg^-1） groups. The CAG rat model was successfully established by inducing with N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） and other factors for a total of 11 weeks. Then， the rats were intervened with fresh and dried D. huoshanense for 4 weeks. The serum and gastric tissues of the rats were collected. The changes in gastric juice secretion volume and gastric acid pH value in each group were observed. The gastric mucosal injury was observed by naked eyes and hematoxylin-eosin（HE） staining. The gastric mucus secretion level was determined by Alcian blue and periodic acid-Schiff staining（AB-PAS） staining. The expression levels of tight junction proteins Occludin and ZO-1 in gastric tissues were determined by immunofluorescence. The expression levels of serum pepsinogen Ⅰ （PG Ⅰ）， pepsinogen Ⅱ （PG Ⅱ）， gastrin 17 （G-17）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， and aquaporin 4 （AQP4） in gastric tissues were determined by Western blot. ResultsCompared with the normal group， the model group showed an obviously reduced gastric juice secretion volume （P0.05）， significantly increased gastric acid pH value （P0.01）， gastric mucosa with obvious atrophy， and a significantly reduced gastric mucus secretion volume （P0.01）. The expression of Occludin and ZO-1 in the gastric mucosal barrier was significantly decreased （P0.01）. The levels of PG Ⅰ and PG Ⅱ in the serum were obviously decreased （P0.05， P0.01）， and the levels of G-17， IL-1β， IL-6， and TNF-α were significantly increased （P0.01）. The expression level of AQP1 in the gastric tissue was significantly upregulated （P0.01）， and the expression levels of AQP3 and AQP4 were significantly downregulated （P0.01）. Compared with the model group， each drug administration group could improve the gastric mucosal atrophy of CAG model rats to varying degrees， obviously increase the gastric juice secretion volume of the model rats （P0.05， P0.01）， significantly decrease the gastric acid pH value （P0.01）， obviously increase the gastric mucus secretion volume （P0.05， P0.01）， obviously decrease the expression levels of G-17， IL-6， IL-1β， and TNF-α （P0.05， P0.01）， obviously increase the expression levels of Occludin， ZO-1， PG Ⅰ， and PG Ⅱ （P0.05， P0.01）， obviously upregulate the expression levels of AQP3 and AQP4 （P0.05， P0.01）， and obviously downregulate the expression level of AQP1 （P0.05， P0.01）. ConclusionThe water extracts of fresh and dried D. huoshanense can exert therapeutic effects on CAG by improving gastric mucosal injury， reducing inflammation， and regulating water metabolism. Moreover， the dried D. huoshanense has a better effect.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective To explore the effect and mechanism of Chir99021 on osteogenic differentiation of rat dental pulp stem cells. Methods Primary rat dental pulp stem cells were isolated from rat dental pulp and verified by fluorescence immunoassay. Different concentrations of Chir99021 were set, and the cell proliferation was detected by CCK⁃8 to select the optimal concentration. Osteogenic differentiation was detected by alizarin red staining. The expression of osteogenic differentiation related genes and proteins recombinant wingless type MMTV integration site famity member 1 (Wnt1), Wnt3a and Wnt3a β⁃expression of catenin, axis inhibition protein 2(Axin 2), dentin sialophosphoprotein(OCN) and dentin matrix acidic phosphoprotein 1(DMP1) was detected by Real⁃time PCR and Western blotting. Results The positive expression of dentin sialophosphoprotein (DSPP) and vimentin indicated that rat dental pulp stem cells were successfully isolated. After osteogenic induction of rat dental pulp stem cells, calcium deposits significantly increased with the addition of glycogen synthase kinase⁃3β(GSK⁃3β) inhibitor Chir99021, calcium deposits were significanted reduced. After osteogenic differentiation of rat dental pulp stem cells, the expression of Wnt1, Wnt3a, β⁃catenin, Axin2, OCN and DMP1 increased, while the expression of Wnt1, Axin2, OCN and DMP1 decreased with the addition of Chir99021. Conclusion Chir99021 can inhibit the osteogenic differentiation of rat dental pulp stem cells after 7 days of induction.