This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC) and explore the potential molecular mechanism of Weifuchun Capsules(WFC) in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group. The normal feeding group received a regular diet, while the modeling group was subjected to the disease-syndrome combined modeling of PLGC. Specifically, the rats had free access to the water containing 120 μg·mL~(-1) N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding). After 15 weeks, the rats in the normal feeding group were randomized into control, control-NF-κB activator betulinic acid(C-BA), and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC) groups. Meanwhile, the rats in the modeling group continuously underwent the modeling procedure and were randomized into model, WFC, model-NF-κB activator(M-BA), and model-NF-κB inhibitor(M-PDTC) groups. The model group and control group were given aseptic water by intragastric administration, once a day. WFC was given at a dose(432 mg·kg~(-1)) 6 times the equivalent dose for adults(body weight: 60 kg) by gavage, once a day. The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg~(-1), twice a week. The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg~(-1), twice a week. The interventions were carried out for 4 weeks. Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE) and alcian blue-periodic acid Sthiff(AB-PAS) staining. The levels of inflammatory cytokines including interleukin(IL)-1β, IL-6, IL-18, tumor necrosis factor-alpha(TNF-α), and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of proteins associated with the NF-κB/NLRP3 inflammasome in the gastric mucosa were determined by Western blot. The positive expression areas of proteins related to NF-κB/NLRP3 inflammasome in the gastric mucosa were measured by immunohistochemistry. The results showed that compared with the control group, the model, C-BA, and M-BA groups showed significantly risen scores of mucosal inflammation, degree of inflammatory activity, gland atrophy, and intestinal metaplasia, and the model and M-BA groups showed significanly risen scores of dysplasia. Compared with the model group, the WFC group demonstrated significantly declined scores of mucosal inflammation and degree of inflammatory activity, as well as declined scores of intestinal metaplasia and dysplasia. Compared with the control group, the model and C-BA groups showed significantly elevated levels of IL-1β, IL-6, IL-18, and TNF-α in the gastric tissue, and the model group showed significantly elevated level of IL-10. In addition, the model and C-BA groups showed significantly up-regulated expression of NF-κB p65, NLRP3, cysteine-aspartic acid protease 1(caspase-1), and apoptosis-associated speck-like protein containing a CARD(ASC) in the gastric mucosa and increased positive expression areas of NF-κB p65, NLRP3, and ASC. Compared with the model group, the WFC group showed significantly decreased levels of IL-1β, IL-6, IL-18, TNF-α, and IL-10 in the gastric tissue, and the M-PDTC group showed significantly lowered levels of IL-1β, IL-18, and TNF-α in the gastric mucosa. Both WFC and M-PDTC groups demonstrated significantly down-regulated expression levels of NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), NLRP3, and caspase-1 in the gastric mucosa, along with significant decreases in the positive expression areas of NF-κB p65, NLRP3, and ASC. In conclusion, the pathogenesis of PLGC is closely related to the activation of the NF-κB/NLRP3 inflammasome signaling pathway. WFC can alleviate mucosal inflammation, inhibit glandular atrophy, partially reverse intestinal metaplasia, and reduce dysplasia to delay the process of inflammation-cancer transformation, and meanwhile it can effectively lower the levels of inflammatory cytokines and down-regulate the expression of pathway-related proteins in the stomach. Therefore, WFC may treat PLGC by inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.
Animals ; Male ; NF-kappa B/genetics* ; Rats ; Rats, Wistar ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Stomach Neoplasms/pathology* ; Inflammasomes/genetics* ; Humans ; Precancerous Conditions/metabolism* ; Capsules

OBJECTIVE: To investigate the clinical efficacy and advantages of robot-assisted total knee arthroplasty (TKA) in patients with varus knee osteoarthritis. METHODS: Between October 2022 and June 2023, a total of 59 patients with severe knee osteoarthritis resulting in varus were treated with total knee arthroplasty, aged from 59 to 81 years with an average (70.90±4.63) years, including 19 mals and 40 females. The patients were divided into two groups based on the surgical method used:28 patients in the robot group and 31 patients in the traditional group. The robot group consisted of 8 males and 20 femalse patients, with an average age of (70.54±4.80) years and an average disease duration of (14.89±8.72) months. The traditional group consisted of 11 males and 20 females patients, with an average age of (71.39±4.5) years and an average disease duration of (12.32±6.73) months. The operative duration, amount of bleeding during the operation, postoperative activity time after the operation, hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and complications were compared between the two groups before and after the operation. Lateral tibia component (LTC), frontal tibia component (FTC), frontal femoral component (FFC) and lateral femoral component (LFC) were measured 6 months after operation Additionally, the degree of knee joint motility, American Knee Society score (KSS), and visual analogue scale(VAS) were compared before and after the operation. RESULTS: All patients had gradeⅠwound healing without any complications, and all patients were followed up for 6 to 8 months, with an average of (6.5±1.5) months. There were no significant differences preoperative imaging evaluation indexes (including HKA, LDFA, and MPTA), preoperative knee mobility, preoperative VAS, and preoperative KSS between the two groups (P>0.05). Comparing the operation time (109.11±7.16) min vs. (83.90±7.85) min, length of the incision (16.60±2.33) cm vs. (14.47±1.41) cm, intraoperative bleeding (106.93±6.15) ml vs. (147.97±7.62) ml, postoperative activity time (17.86±1.84) h vs. (21.77±2.68) h, between the two groups showed statistically significant differences (P<0.05). There were significant differences in FFC (88.96±0.84)° vs. (87.93±1.09)° and LFC (88.57±1.10)° vs. (87.16±1.2)° between the two groups at 6 months after operation (P<0.05). The robotic group 1, 3, 6 months after KSS (75.96±3.96), (81.53±3.78), (84.50±3.29) scores, VAS (3.68±0.67), (2.43±0.79), (0.54±0.64), knee joint mobility (113.32±4.72) °, (123.93±3.99) °, (135.36±2.34) °;Traditional group KSS (73.77±4.18), (76.48±3.60), (80.19±3.28) scores, VAS (4.16±1.04), (3.03±0.75), (1.42±0.76) scores, knee joint mobility (109.19±6.95) °, (119.94±6.08) °, (134.48±2.14) °. Compared to before surgery, both groups showed significant improvement in KSS, VAS and knee mobility during the three follow-up visits (P<0.001). Additionally, postoperative HKA (180.39±1.95)° vs. (178.52±2.23)°, LDFA (89.67±0.63) ° vs. (89.63±0.63)°, and MPTA (89.44±0.55)° vs. (89.29±0.60)° were significantly improved in both groups compared to before surgery (P<0.001). The robotic group had higher KSS than the traditional group at 1, 3, and 6 months after surgery (P<0.05). The robotic group also had lower VAS than the traditional group at 1, 3, and 6 months after surgery (P<0.05). Furthermore, knee mobility was higher in the robotic group than those in the traditional group at 1 and 6 months after surgery (P<0.05), but there was no significant difference between the two groups at 6 months after surgery. CONCLUSION Robot-assisted total knee arthroplasty is a safe and effective method for total knee replacement. The use of robotics can improve the limb axis and prosthesis alignment for patients with preoperative varus deformity, resulting in better clinical and imaging outcomes compared to the conventional group.
Humans ; Female ; Male ; Arthroplasty, Replacement, Knee/methods* ; Aged ; Middle Aged ; Osteoarthritis, Knee/physiopathology* ; Aged, 80 and over ; Robotic Surgical Procedures/methods*

BACKGROUND: Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients. METHODS: In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients. RESULTS: A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer. CONCLUSIONS Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.

Objective: To investigate the causes and characteristics of immune hemolytic transfusion reactions (HTRs) triggered by anti-E antibodies, so as to provide a scientific reference for guaranteeing clinical blood transfusion safety. Methods: Five patients who experienced HTRs in our hospital from November 2023 to October 2024 were selected as the research subjects. ABO/RhD blood grouping, antibody screening, antibody identification, and the direct antiglobulin test (DAT) were conducted using the column agglutination method. The causes of HTRs in these patients were investigated using multiple techniques such as the two-step enzyme method, polyethylene glycol (PEG), acid elution technique, and capillary centrifugation method. Results: All five patients tested negative for antibody screening prior to transfusion. However, after transfusion of E+ phenotyped blood, patients 1, 2, 3, and 5 developed delayed haemolytic transfusion reaction (DHTR), while patient 4 experienced acute haemolytic transfusion reaction (AHTR). Anti-E antibodies were detected in all blood samples from the patients after the hemolytic transfusion reaction, including the enzyme-only anti-E antibody in two cases. Conclusion: Anti-E antibody can trigger both intravascular and extravascular hemolysis. It is recommended to conduct ABO/RhD and RhE antigen-matched transfusions and establish a regional blood transfusion database to reduce immune hemolytic transfusion reactions caused by anti-E antibody.

Objective To explore the risk factors related to afterload mismatch(AM)after transcatheter mitral valve repair(MitraClip).Methods This was a retrospective cohort study.48 patients hospitalized in the Department of Cardiovascular Medicine,the First Affiliated Hospital of Sun Yat-sen University from December 2021 to December 2023,who underwent MitraClip due to severe mitral regurgitation(MR)were included.Preoperative clinical data,laboratory tests,and preoperative and postoperative color Doppler echocardiographic examination results of surgical patients were collected.AM was defined as the left ventricular ejection fraction(LVEF)decreased by 15％or more after surgery compared with the one before(dLVEF≤-15％).Patients were divided into AM group and non-AM group according to whether afterload mismatch occurred.Univariate and multivariate logistic regression were used to analyze the risk factors of postoperative AM.Results Among 48 patients who underwent MitraClip,14 of them(29.2％)developed afterload-mismatched.For those without AM,their overall LVEF was improved after the operation;for patients in both AM group and non-AM group,their overall left ventricular end-diastolic diameter(LVEDd),left ventricular end-diastolic diameter volume index(LVEDVi)was reduced compared with the preoperative ones.Univariate regression analysis showed that C-reactive protein levels(OR 1.98,95％CI 1.02-3.83),platelets(OR 2.22,95％CI 1.08-4.53),systemic immune inflammation index(OR 1.96,95％CI 1.03-3.71)were associated with an increased risk of AM in patients undergoing MitraClip(all P＜0.05),while those with larger right atrial diameter(OR 0.35,95％CI 0.13-0.93)or moderate to severe tricuspid regurgitation(OR 0.19,95％CI 0.05-0.81)were less likely to develop into AM(both P＜0.05),which is still satisfied after adjustment.Conclusions For patients who underwent MitraClip,C-reactive protein levels,platelets and systemic immune inflammation index(SII)are associated with an increased risk of afterload mismatched,while those with larger right atrial diameter or moderate to severe tricuspid regurgitation were less likely to develop into AM.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Objective:To analyze the occurrence of concomitant gene mutations in cytogenetically normal acute myeloid leukemia(CN-AML)patients with CEBPA mutation and its impact on the clinical characteristics and prognosis of the patients.Methods:151 newly diagnosed patients with CN-AML in the Second Hospital of Shanxi Medical University from June 2013 to June 2020 were analyzed retrospectively.34 common genetic mutations associated with hematologic malignancies were detected by next-generation sequencing technology.The occurrence of concomitant gene mutations in patients with CEBPA positive and negative groups was compared,and the correlation between concomitant mutations in different functional groups and the clinical characteristics and prognosis of CN-AML patients with CEBPA mutation was analyzed.Results:In 151 patients with CN-AML,55(36.42％)were positive for CEBPA mutation(including 36 cases of CEBPAdm and 19 cases of CEBPAsm),of which 41(74.55％)had co-mutations with other genes.The main mutated genes were GATA2(25.45％,14/55),TET2(21.82％,12/55),FLT3(20.00％,11/55),NRAS(12.73％,7/55)and WT1(9.09％,9/55),etc.Some cases had two or more concomitant gene mutations.Grouping the mutant genes according to their functions showed that CEBPA+group had lower mutation rates of histone methylation(P=0.002)and chromatin modification genes(P=0.002,P=0.033),and higher mutation rates of transcription factors(P=0.037)than CEBPA-group.In 55 patients with CEBPA+CN-AML,the platelet count at diagnosis in signaling pathway gene mutation-positive group was lower than that in the mutation-negative group(P=0.005),the proportion of bone marrow blasts in transcription factor mutation-positive group was higher than that in the mutation-negative group(P=0.003),and the onset age in DNA methylation gene mutation-positive group and chromatin modifier mutation-positive group was older than that in the mutation-negative group,respectively(P=0.002,P=0.008).DFS of CEBPA+CN-AML patients in signaling pathway gene mutation group was shorter than that in signaling pathway gene mutation-negative group(median DFS:12 months vs not reached)(P=0.034).Compared with DNA methylation gene mutation-negative group,CEBPA+CN-AML patients with DNA methylation gene mutation had lower CR rate(P=0.025)significantly shorter OS and DFS(median OS:20 months vs not reached,P=0.006;median DFS:15 months vs not reached,P=0.049).OS in patients with histone methylation gene mutation was significantly shorter than that in the histone methylation gene mutation-negative group(median OS:12 months vs 40 months)(P=0.008).Multivariate analysis of prognostic factors showed that the proportion of bone marrow blasts(P=0.046),concomitant DNA methylation gene mutation(P=0.006)and histone methylation gene mutation(P=0.036)were independent risk factors affecting the prognosis.Conclusion:CN-AML patients with CEBPA mutation have specific concomitant gene profile,and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.

Objective:To analyze the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL)in real-world.Methods:The clinical data of 1414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed.Treatment failure was defined as relapse,non-relapse death,and secondary tumor.Results:Following-up for median time 49.7 (0.1-136. 9)months,there were 269 cases (19.0％)treatment failure,including 140 cases (52.0％)relapse,and 129 cases (48.0％)non-relapse death.Cox univariate and multivariate analysis showed that white WBC≥50 ×109/L at newly diagnosis,acute T-cell lymphoblastic leukemia (T-ALL),BCR-ABL1,KMT2A-rearrangement and poor early treatment response were independent risk factor for treatment failure (all HR>1.000,P<0.05).The 5-year OS of 140 relapsed ALL patients was only 23.8％,with a significantly worse prognosis for very early relapse (relapse time within 18 months of diagnosis).Among 129 patients died from non-relapse death,71 cases (26.4％)were died from treatment-related complications,56 cases (20.8％)died from treatment abandonment,and 2 cases (0.7％)died from disease progression.Among them,treatment-related death were significantly correlated with chemotherapy intensity,while treatment abandonment were mainly related to economic factors.Conclusion:The treatment failure of children with ALL in our province is still relatively high,with relapse being the main cause of treatment failure,while treatment related death and treatment abandonment caused by economic factors are the main causes of non-relapse related death.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.

Aim To investigate the effects of the phos-phodiesterase 8(PDE8)inhibitor PF-04957325 on learning and memory,anxiety and depression in Alzhe-imer's disease(AD)mice induced by Okadaic acid(OA),and to explore its mechanism.Methods Twenty-one 2-month-old male C57BL/6J mice were se-lected for the experiment and randomly divided into the control group,AD model group,and PDE8 inhibitor group(0.1 mg·kg-1).AD model was induced by bi-lateral hippocampal localization injection of OA(50 ng on each side)in the model and PDE8 inhibitor groups of mice.Two days after the injection of OA,PDE8 in-hibitor group was given 0.1 mg·kg-1 drug,while the AD model groups and control group were given with the same volume of vehicle for 21 consecutive days.On day 13 of inhibitor administration,behavioral tests re-lated to learning and memory abilities,anxiety and de-pressive behaviors were performed in mice.HE stai-ning was used to observe the morphology of neuronal cells in the DG,CA1,and CA3 regions of the hippo-campus of mice,and Western blot was used to detect the levels of phosphorylated Tau proteins at different sites within the hippocampus of mice as well as the ex-pression of proteins related to the PDE8/cAMP/CREB pathway.Results Compared with the control group,the Y-maze Spontaneous alternation,Recognition index of NOR and Latency of PAT were significantly shorter(P＜0.01),and Entries times、Time in the target quadrant of MWM were reduced(P＜0.05)in the AD model group,which showed a decrease in the ability of learning and memory,whereas the administration of PF-04957325 significantly improved the ability of learning and memory in the AD mice;mice in the AD model group showed a significant decrease in the num-ber of entries into the central area of the OFT and the time spent in the central area(P＜0.05),and a sig-nificant increase in the Immobility time of TST(P＜0.01),suggesting that the mice had anxiety and de-pression,and the administration of PF-04957325 did not improve the anxious behavior of the mice,but im-proved the depressed behavior to a certain extent;the hippocampus of the AD model group mice showed ker-nel solidification in the DG,CA1 and CA3 regions,and neurons were not neatly arranged,and the admin-istration of PF-04957325 could alleviate the damage of hippocampal nerve cells in mice.Compared with the control group,the phosphorylation levels of Tau protein Ser1 99,Ser396 and Ser202 sites in the hippocampus of mice in the AD model group were significantly in-creased(P＜0.01),the expression of PDE8A and PDE8B proteins was significantly increased(P＜0.01),and the expression of p-PKA/PKA and BDNF proteins was decreased(P＜0.05),after administra-tion of PF-04957325,the phosphorylation levels of Tau protein Ser396 and Ser202 sites were significantly re-duced(P＜0.01),PDE8A and PDE8B protein ex-pression was significantly decreased(P＜0.01),and p-PKA/PKA,p-CREB/CREB and BDNF protein ex-pression was significantly increased(P＜0.01).Con-clusion PDE8 inhibitor PF-04957325 can improve learning memory ability,reduce cognitive dysfunction,restore Tau protein function,and attenuate neuronal cell damage in the hippocampus of AD mice with amel-iorative effects.The mechanism of action may be relat-ed to the activation of PDE8/cAMP/CREB pathway and inhibition of Tau protein phosphorylation.