Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Objective:To investigate the effects of different doses of whole abdominal ultra‐high dose rate (FLASH) irradiation on the intestinal microbiota of mice.Methods:A total of 25 healthy male C57BL/6J mice were randomly divided into the control ( n=5) and FLASH irradiation groups ( n=20) by simple randomization method, and the FLASH irradiation group was further divided into different radiation dose subgroups of 10, 15, 20, 25 Gy, 5 in each group. The mice were irradiated with a single whole abdomen at a dose rate of 100 Gy/s, then sacrificed 3.5 d after irradiation. Fresh fecal specimens and intestinal tissues of mice were collected for 16S rRNA sequencing, microbiota analysis, hematoxylin eosin (HE) staining and injury severity score analysis. Two-group comparison was performed by independent sample t-test. Multi-group comparison was conducted by one-way ANOVA. Results:HE staining revealed that the whole abdomen FLASH irradiation caused varying degree of intestinal injury in mice, and the intestinal injury reaction was aggravated with the increase of irradiation dose. β‐diversity analyses showed that there were differences in the composition of intestinal microbiota between FLASH irradiation group and control group ( P=0.001), but the differences in the relative abundance of the species between the irradiation groups at different doses were relatively small, and there were their own dominant genera of bacteria. Comparison of different doses of FLASH irradiation groups with control group screened out 16 species of bacteria with shared differences at the genus level, in which Lactobacillus, Ligilactobacillus and unclassified Lactobacillus were more abundant in the control group, while Escherichia, Allobaculum, and Muribaculum were more abundant in the FLASH irradiation groups. Conclusions:The whole‐abdominal FLASH irradiation induces intestinal damage in mice, and the intestinal damage response is worsened with the increase of irradiation dose. Different doses of whole abdominal FLASH irradiation alter the intestinal microbiota composition of mice. Sixteen species of common intestinal differential microbiota at the genus level are screened out in the different doses of FLASH irradiation groups compared with the control group, which may serve as a marker for measuring intestinal injury in mice irradiated with whole‐abdominal FLASH.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To analyze the efficacy and safety of modified associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of patients with primary liver cancer.Methods:Clinical data of 83 patients with hepatocellular carcinoma (HCC) undergoing hemihepatectomy in the Department of Hepatobiliary and Pancreatic Tumor Surgery of Gansu Provincial Cancer Hospital between January 2022 and November 2023 were retrospectively analyzed, including 53 males and 30 females, aged (54.0±6.5) years. According to the treatment protocol, patients were divided into the control group ( n=41), in which patients underwent traditional ALPPS, and the observation group ( n=42), in which patients underwent modified ALPPS (occlusion of portal venous branch using vascular clips, combined with radiofrequency ablation for physical separation of the diseased lobe, without liver mobilization). The completion rate of staged surgery, interval between surgeries, future liver remnant (FLR) growth rate at 7 days after first-stage surgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels at 5 days after fisrt-stage surgery, and postoperative complications (ascites, nausea, and vomiting, etc.) were compared between the groups. Results:The completion rate of staged surgery was 95.2% (40/42) in the observation group and 90.2% (37/41) in the control group ( χ2=0.62, P=0.431). The ALT and AST levels at 5 days after first-stage surgery were (550.4±86.0) U/L and (327.1±52.8) U/L in the observation group, respectively, which were significantly lower than those in the control group (861.6±106.3) U/L and (533.8±73.7) U/L, respectively ( t=13.13 and P<0.001, t=12.93 and P<0.001). The FLR growth rate were higher in the observation group than that in the control group [(80.4±10.3)% vs (49.3±5.7)%; t=13.13, P<0.001] and the interval between procedures were also shorter in the observation group (10.9±2.1 vs 22.4±4.8, d; t=9.65, P<0.001). The intraoperative blood loss of the first-stage surgery was lower in the observation group than that in the control group (350.5±45.2 vs 825.5±21.7, ml; t=21.43, P<0.001). The total complication rates after the first-stage surgery were 11.9% (5/42) in the observation group and 19.5% (8/41) in the control group, while after the second-stage surgery, the complication rates were 7.5% (3/40) and 18.9% (7/37), respectively, with no statistically significant differences ( χ2=0.65 and P=0.419, χ2=1.81 and 0.177, respectively). Conclusion:The modified ALPPS offers better postoperative liver function, reduced surgical trauma, accelerated FLR growth, and a shorter interval between procedures, demonstrating a favorable safety in the treatment of primary liver cancer.

Objective To investigate the diagnostic efficacy of targeted biopsy(TB)combined with ipsilateral hemiglandular systematic biopsy(SB)of the dominant lesion,so as to explore a novel reduced-core biopsy strategy.Methods A retrospective analysis was conducted on the clinical data of 299 patients treated in our hospital during Sep.1,2022,and Feb.28,2023,who had a Prostate Imaging Reporting and Data System(PI-RADS)score ≥3 and underwent combined TB and SB.The dominant lesion was defined as the lesion with the highest PI-RADS score on multi-parametric magnetic resonance imaging(mpMRI);in cases of identical scores,the largest was designated as the dominant.SB was categorized as ipsilateral(ipsi-SB)or contralateral(contra-SB)to the dominant lesion.The consistency in detecting clinically significant prostate cancer(csPCa)was compared between TB with ipsi-SB(TB+ipsi-SB),TB with contra-SB(TB+contra-SB),and TB with SB(TB+SB).Subgroup analyses were performed based on PI-RADS score,prostate-specific antigen(PSA)level,prostate volume(PV),and mpMRI lesion distribution to evaluate csPCa detection rates across different variables.Results TB+ipsi-SB demonstrated comparable detection rate to TB+SB(46.2％vs.46.8％).The K values for TB+ipsi-SB and TB+contra-SB relative to TB+SB were 0.987(95％CI:0.969-1.000,P＜0.01)and 0.933(95％CI:0.892-0.974,P＜0.01),respectively.Across all subgroups,TB+ipsi-SB showed the highest agreement with TB+SB.Notably,in subgroups with PI-RADS 3 and 5,PSA＞0-20 ng/mL,PV＜25 mL,bilateral or multiple mpMRI lesions,TB+ipsi-SB achieved complete concordance with TB+SB in csPCa detection[K=1.000(95％CI:1.000-1.000),P＜0.01].Conclusion For patients with PI-RADS score ≥3,TB+ipsi-SB exhibits near-perfect consistency with TB+SB in csPCa detection while requiring fewer biopsy cores.TB+ipsi-SB represents a promising refinement of the TB+SB approach.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective:To investigate the clinical efficacy of application of Shexiang Tongxin Dropping Pills in patients with coronary heart disease and heart failure due to qi deficiency and blood stasis syndrome. Methods:A prospective study was conducted with 66 patients with coronary heart disease and heart failure, all diagnosed with qi deficiency and blood stasis syndrome, who were admitted to the Department of Internal Medicine at Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine from January 2023 to March 2024. The patients were divided into a control group and an observation group, each consisting of 33 patients, based on the odd or even number of their hospital admission numbers. The control group received conventional treatment with Western medicine, while the observation group received Shexiang Tongxin Dropping Pills in addition to the treatment given to the control group. The clinical effects between the two groups were compared, and changes in heart function, traditional Chinese medicine syndrome scores, and serum biomarkers before and after treatment were collected and compared. Results:The overall response rate in the observation group was 96.97% (32/33), which was significantly higher than that of the control group at 75.76% (25/33) ( χ2 = 4.63, P < 0.05). After treatment, the traditional Chinese medicine syndrome scores in the observation group were significantly lower than those in the control group ( t = 9.03, 6.36, 5.55, 12.34, all P < 0.001). The left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular end-diastolic volume in the observation group were all lower than those in the control group ( t = 3.66, 7.69, 6.53, all P < 0.05). The 6-minute walk test results and left ventricular ejection fraction in the observation group were significantly higher than those in the control group ( t = -5.06, -18.10, both P < 0.001). The levels of N-terminal pro B-type natriuretic peptide, high-sensitivity C-reactive protein, and serum homocysteine in the observation group were all lower than those in the control group ( t = 18.09, 18.61, 10.87, all P < 0.001). Conclusions:Combining Shexiang Tongxin Dropping Pills with conventional treatment for patients with coronary heart disease and heart failure due to qi deficiency and blood stasis syndrome can effectively enhance clinical outcomes, alleviate symptoms, improve heart function, and reduce inflammatory responses.

Objective To investigate the diagnostic efficacy of targeted biopsy(TB)combined with ipsilateral hemiglandular systematic biopsy(SB)of the dominant lesion,so as to explore a novel reduced-core biopsy strategy.Methods A retrospective analysis was conducted on the clinical data of 299 patients treated in our hospital during Sep.1,2022,and Feb.28,2023,who had a Prostate Imaging Reporting and Data System(PI-RADS)score ≥3 and underwent combined TB and SB.The dominant lesion was defined as the lesion with the highest PI-RADS score on multi-parametric magnetic resonance imaging(mpMRI);in cases of identical scores,the largest was designated as the dominant.SB was categorized as ipsilateral(ipsi-SB)or contralateral(contra-SB)to the dominant lesion.The consistency in detecting clinically significant prostate cancer(csPCa)was compared between TB with ipsi-SB(TB+ipsi-SB),TB with contra-SB(TB+contra-SB),and TB with SB(TB+SB).Subgroup analyses were performed based on PI-RADS score,prostate-specific antigen(PSA)level,prostate volume(PV),and mpMRI lesion distribution to evaluate csPCa detection rates across different variables.Results TB+ipsi-SB demonstrated comparable detection rate to TB+SB(46.2％vs.46.8％).The K values for TB+ipsi-SB and TB+contra-SB relative to TB+SB were 0.987(95％CI:0.969-1.000,P＜0.01)and 0.933(95％CI:0.892-0.974,P＜0.01),respectively.Across all subgroups,TB+ipsi-SB showed the highest agreement with TB+SB.Notably,in subgroups with PI-RADS 3 and 5,PSA＞0-20 ng/mL,PV＜25 mL,bilateral or multiple mpMRI lesions,TB+ipsi-SB achieved complete concordance with TB+SB in csPCa detection[K=1.000(95％CI:1.000-1.000),P＜0.01].Conclusion For patients with PI-RADS score ≥3,TB+ipsi-SB exhibits near-perfect consistency with TB+SB in csPCa detection while requiring fewer biopsy cores.TB+ipsi-SB represents a promising refinement of the TB+SB approach.

Objective:To analyze the efficacy and safety of modified associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of patients with primary liver cancer.Methods:Clinical data of 83 patients with hepatocellular carcinoma (HCC) undergoing hemihepatectomy in the Department of Hepatobiliary and Pancreatic Tumor Surgery of Gansu Provincial Cancer Hospital between January 2022 and November 2023 were retrospectively analyzed, including 53 males and 30 females, aged (54.0±6.5) years. According to the treatment protocol, patients were divided into the control group ( n=41), in which patients underwent traditional ALPPS, and the observation group ( n=42), in which patients underwent modified ALPPS (occlusion of portal venous branch using vascular clips, combined with radiofrequency ablation for physical separation of the diseased lobe, without liver mobilization). The completion rate of staged surgery, interval between surgeries, future liver remnant (FLR) growth rate at 7 days after first-stage surgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels at 5 days after fisrt-stage surgery, and postoperative complications (ascites, nausea, and vomiting, etc.) were compared between the groups. Results:The completion rate of staged surgery was 95.2% (40/42) in the observation group and 90.2% (37/41) in the control group ( χ2=0.62, P=0.431). The ALT and AST levels at 5 days after first-stage surgery were (550.4±86.0) U/L and (327.1±52.8) U/L in the observation group, respectively, which were significantly lower than those in the control group (861.6±106.3) U/L and (533.8±73.7) U/L, respectively ( t=13.13 and P<0.001, t=12.93 and P<0.001). The FLR growth rate were higher in the observation group than that in the control group [(80.4±10.3)% vs (49.3±5.7)%; t=13.13, P<0.001] and the interval between procedures were also shorter in the observation group (10.9±2.1 vs 22.4±4.8, d; t=9.65, P<0.001). The intraoperative blood loss of the first-stage surgery was lower in the observation group than that in the control group (350.5±45.2 vs 825.5±21.7, ml; t=21.43, P<0.001). The total complication rates after the first-stage surgery were 11.9% (5/42) in the observation group and 19.5% (8/41) in the control group, while after the second-stage surgery, the complication rates were 7.5% (3/40) and 18.9% (7/37), respectively, with no statistically significant differences ( χ2=0.65 and P=0.419, χ2=1.81 and 0.177, respectively). Conclusion:The modified ALPPS offers better postoperative liver function, reduced surgical trauma, accelerated FLR growth, and a shorter interval between procedures, demonstrating a favorable safety in the treatment of primary liver cancer.