Objective To compare effectiveness between the modified and traditional pressure-overload myocardial hypertrophy(POMH) model by abdominal aorta coarctation (AAC) method. Methods Totally 45 rats were divided into three groups(n = 15 per group), sham group, traditional group, and modified group. In the traditional group, the diameter ol the abdominal aorta was narrowed to 0. 70 mm through a midline incision for 4 weeks; in the modified group, the diameter of the abdominal aorta was narrowed above the left kidney to 0. 45 mm for 1 week, and then the narrowing was lifted postoperatively. The cardiac index, heart weight (HW) /body weight (BW) and left ventricular index, left ventricular weight (LVW)/BW were measured from the heart specimens, and the cross-sectional area of cardiac myocytes, myocardial collagen area, and myocardial collagen area Iraction were measured in the pathological sections by HE staining and Masson staining. Results Compared with the sham group, the differences in end-systolic interventricular septum thickness (IVSs), left ventricular end-systolic posterior wall thickness (LVPWs), HW/BW, LVW/BW, cardiomyocyte cross-sectional area, myocardial collagen area, myocardial collagen area fraction, and brain natriuretic peptide (BNP) expression levels were statistically significant (P<0. 05) in the modilied and traditional groups of rats. The differences in these indices were not statistically significant between the modified and traditional groups (P>0. 05). Conclusion The modified abdominal aortic constriction method used in this experiment is time-saving, stable, homogeneous and easy to replicate, and is a more ideal approach to establish a rat model of POMH.

This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m²·g^-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m²·g^-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Purpose::Minimal data exist on brain injury in patients with exertional heatstroke (EHS) in developing country. In this study, we explored the risk factors for brain injury induced by EHS 90-day after onset.Methods::A retrospective cohort study of patients with EHS was conducted in the intensive care unit of the General Hospital of Southern Theater Command of PLA in China from April 2014 to June 2019. Patients were divided into non-brain injury (fully recovered) and brain injury groups (comprising deceased patients or those with neurological sequelae). The brain injury group was further subdivided into a death group and a sequela group for detailed analysis. General information, neurological performance and information on important organ injuries in the acute stage were recorded and analysed. Multivariable logistic regression was used to identify risk factors for brain injury after EHS and mortality risk factors for brain injury, and Kaplan-Meier survival curve was used to evaluate the effect of the neurological dysfunction on survival.Results::Out of the 147 EHS patients, 117 were enrolled, of which 96 (82.1%) recovered, 13 (11.1%) died, and 8 (6.8%) experienced neurological sequelae. Statistically significant differences were found between non-brain injury and brain injury groups in age, hypotension, duration of consciousness disorders, time to drop core body temperature below 38.5°C, lymphocyte counts, platelet counts, procalcitonin, alanine aminotransferase, aspartate aminotransferase, creatinine, cystatin C, coagulation parameters, international normalized ratio, acute physiology and chronic health evaluation II scores, sequential organ failure assessment (SOFA) scores, and Glasgow coma scale scores (all p < 0.05). Multivariate logistic regression showed that age ( OR = 1.090, 95% CI: 1.02 - 1.17, p = 0.008), time to drop core temperature ( OR = 8.223, 95% CI: 2.30 - 29.40, p = 0.001), and SOFA scores ( OR= 1.676, 95% CI: 1.29 - 2.18, p < 0.001) are independent risk factors for brain injury induced by EHS. The Kaplan-Meier curves suggest significantly prolonged survival ( p < 0.001) in patients with early Glasgow coma scale score > 8 and duration of consciousness disorders ≤ 24 h. Conclusions::Advanced age, delayed cooling, and higher SOFA scores significantly increase the risk of brain injury post-EHS. These findings underscore the importance of rapid cooling and early assessment of organ failure to improve outcomes in EHS patients.

Objective To explore clinical effect of modified Chinese-way technique under shoulder arthroscopy in treating massive rotator cuff tears.Methods From January 2019 to June 2022,22 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair with improved Chinese-way technique,including 10 males and 12 females,aged from 46 to 76 years old with an average of(64.14±7.45)years old;the courses of disease ranged from 5 to 14 months with an average of(8.32±2.42)months;19 patients were complete repaired,and 3 patients were partial repaired.Visual analogue scale(VAS)and University of California at Los Angeles(UCLA)scale were used to evaluate pain and function of shoulder joint preopera-tively and 1 year postoperatively.Postoperative complications,the integrity of reconstructed tissue structure and the size of sub-acromial space were observed.Results All patients were followed up from 12 to 34 months with an average of(17.14±5.93)months.Re-tear were occurred in 4 patients during MRI follow-up,but clinical symptoms of patients were improved significant-ly and they were satisfied with the treatment,the others were no complications such as incision infection,peripheral nerve in-jury,loosening and falling off of internal fixation anchors.Preoperative and 1 year after operation VAS were(8.05±1.12)and(1.82±1.50),UCLA scores were(7.45±1.65)and(31.41±2.87)respectively,and the difference was statistically significant(P＜0.05).Conclusion The modified Chinese-way technique under shoulder arthroscopy for the massive rotator cuff tear could relieve pain obviously and recovery postoperative function well,with satisfactory curative effect.

The anti-apoptotic members of Bcl-2 family proteins, Bcl-2 and Mcl-1, are considered therapeutic targets of various cancers. In this article, we developed four hydrophobic tag (HyT)-based protein degraders of Bcl-2/Mcl-1, based on a Bcl-2/Mcl-1 dual inhibitor S1-6, and tested their capability in Bcl-2/Mcl-1 degradation and apoptotic induction in MCF-7 cells. Interestingly, different linkers in the HyT degraders led to selective Bcl-2/Mcl-1 degradation, though the degraders S1-D1-S1-D4 maintained the pan-Bcl-2 family binding capacity. Among them, S1-D2 and S1-D4, two compounds bearing a hydrophobic linker or a PEG linker, were observed to potently and selectively induce the ubiquitination and proteasomal degradation of Bcl-2 and Mcl-1 in living cells, with a degradation rate of more than 80% or 60%, respectively. Moreover, the HyT-based degraders showed increased lethality of cancer cells compared to the parent inhibitor S1-6, demonstrating that the advantage of degraders to the occupancy-based inhibitors.

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.
Male ; Female ; Humans ; Adult ; Treatment Outcome ; Anemia, Aplastic/therapy* ; Retrospective Studies ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hepatitis/etiology* ; Bronchiolitis Obliterans Syndrome ; Transplantation Conditioning

Humans ; Toxoplasmosis ; Hematopoietic Stem Cell Transplantation ; Hematologic Diseases

Purpose To investigate and summarize the clinicopathological features,immunophenotype,diagnosis and differential diagnosis of anaplastic thyroid carcinoma(ATC).Methods The clinicopathological features and follow-up data of 15 patients with ATC were reviewed and retrospectively ana-lyzed,and the histological features,immunophenotypic,and molecular features were observed.Results There were 8 males and 7 females with a mean age of 63.5 years.The largest tumor diameter was 45.9 mm(range,20-73 mm).Macroscopically,the tumors appeared nodular or lobulated,mostly firm to hard,with a cut surface of gray-white or gray-yellow in color,and were accompanied by hemorrhage,necrosis,and cystic changes.Mi-croscopically,the tumor exhibited diverse structures and cellular morphology mainly composed of epithelioid,spindle,multinu-cleated giant cells,rarely rhabdoid morphology(2 cases)and heterologous osteosarcomtoid differentiation(1 case).Two cases showed squamous cell carcinoma morphology as well.Among them,there were pure ATC in 11 cases while three cases had mixed papillary thyroid carcinoma components and one case had coexisting high-grade differentiated thyroid carcinoma compo-nent.Cervical lymph node metastasis was present in 6 cases.CK(AE1/AE3)expression was observed in 80%of the cases while PAX8 expression was seen in53.3%.Varying degrees of BRAF(VE1)expression were found in 42.9%whereas weak focal TTF-1 expression occurred only in two cases;and all cases did not express TG.Overall,genetic testing was performed in 8 cases(53.3%).The TP53 gene was the most frequently muta-ted gene(5/8,62.5%),followed by the RAS(3/8,37.5%)and BRAF(3/8,37.5%)genes,while the TERT combined with PIK3CA gene was mutated in only one case.Moreover,multiple gene mutations occurred simultaneously in five cases.Of the total fourteen patients who underwent follow-up,the mean and median survival times were 13.9 and 5.0 months,respec-tively.The disease-specific mortality rate reached 78.6%.Conclusion ATC is extremely rare,displaying unique histolog-ical characteristics,often accompanied by various gene muta-tions.It has a poor prognosis;therefore,establishing a defini-tive pathological diagnosis provides valuable evidence for predic-ting patient outcomes and guiding clinical management.