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 explore the correlation between colorectal cancer tissue Janus kinase 2(JAK2)gene mutations and T cytokine 3(TCF3)protein expression with clinical pathological characteristics and prognosis,and to provide laboratory reference indicators for early evaluation of the illness severity and prognosis of colorectal cancer.Methods A retrospective analysis was conducted on the data of 50 colorectal cancer patients who were admitted from January 2016 to April 2021 and retained colon cancer and adjacent tissue wax blocks.Basic information,clinical and pathological features such as TNM staging,lymph node metastasis,and 3-year survival prognosis of the patients were collected.The wax blocks of colon cancer and adjacent tissues of patients were detected,in which Taqman fluorescence probe method was applied to detect the distribution of JAK2 gene at the rs2230724 locus AA,AG,and GG genotypes in colon cancer tissues,and immunohistochemistry method was applied to detect the positive expression rate of TCF3 protein in colon cancer and adjacent tissues.The basic information,JAK2 rs2230724 gene mutation,and TCF3 protein expression of patients with different clinical and pathological characteristics were compared,and the influencing factors of clinical and pathological characteristics of colon cancer was analyzed by logistic regression model.Kaplan Meier survival curve was applied to compare the survival prognosis of patients with JAK2 gene mutations and TCF3 protein expression in colorectal cancer tissue,and Cox regression model was applied to analyze the risk factors affecting the prognosis of colorectal cancer patients.Results The positive expression rate of TCF3 protein in colon cancer tissues was higher than that in adjacent tissues(P＜0.05).The age,BMI,proportion of GG genotype at rs2230724 locus of JAK2 gene and positive expression rate of TCF3 protein in TNM stage Ⅲ colon cancer patients were higher than those in TNM stage Ⅰ-Ⅱ patients(P＜0.05);The age,BMI,smoking rate,proportion of GG type at the rs2230724 locus of JAK2 gene in colon cancer tissue,and positive expression rate of TCF3 protein in patients with lymph node metastasis were higher than those without lymph node metastasis(P＜0.05);The results of the logistic regression model analysis showed that the influencing factors of clinical pathological features such as TNM staging and lymph node metastasis in colon cancer were age,mutation of JAK2 gene rs2230724 site in colon cancer tissue,and positive expression rate of TCF3 protein(P＜0.05).The Kaplan Meier survival curve analysis showed that patients with JAK2 gene rs2230724 GG genotype and TCF3 protein positivity in colon cancer tissue had higher cumulative all-cause mortality rates(P＜0.05).The results of univariate and multivariate Cox regression model analysis showed that independent risk factors affecting the prognosis of colorectal cancer patients include JAK2 gene rs2230724 site GG type,TCF3 protein positive expression,TNM stage Ⅲ,lymph node metastasis,and age.Conclusion The proportion of JAK2 gene rs2230724 GG type and TCF3 protein expression in colorectal cancer tissues are related to their clinical pathological characteristics and prognosis,and can be used as reference indicators for evaluating clinical pathological characteristics and predicting prognosis of colorectal cancer.

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

AIM To evaluate the quality of Changmaile Capsules(Ⅰ).METHODS The analysis was performed on a 35℃ thermostatic Thermo Scientific AccucoreTM XL C18 column(4.6 mm×250 mm,4 μm),with the mobile phase comprising of methanol-acetonitrile-0.5% phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,280 nm.The contents of gastrodin,danshensu,quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside,3′-hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin,rosmarinic acid,lithospermic acid,ononin,daidzein,salvianolic acid B,calycosin,paeoniflorin and isoquercitrin were determined,after which HPLC fingerprints were established,along with the calculation of similarities.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 87.4%-103.9% with the RSDs of 0.54%-3.10% .At 230 nm,the fingerprints of ten batches of samples demonstrated similarities of 0.954-0.999,which displayed obvious differences at 280 nm.3′-Hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin and daidzein were main differential constituents,paeoniflorin and isoquercitrin exhibited stable contents in various batches of samples.CONCLUSION This simple,accurate and reliable method can be used for the quality control of Changmaile Capsules(Ⅰ).

Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BβAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BβSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BβAla98Asp and p.BβSer473* were pathogenic. Protein models demonstrated that the p.BβAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BβSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BβAla98Asp heterozygous missense mutation and the p.BβSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.
Humans ; Afibrinogenemia/genetics* ; Codon, Nonsense ; Pedigree ; Phenotype ; Fibrinogen/genetics* ; Genotype

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.
Female ; Humans ; Cervix Uteri/surgery* ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms/surgery* ; Carcinoma, Neuroendocrine/surgery* ; Recurrence

Objective To design a mobile container-based negative pressure chamber compatible with kinds of carriers to isolate and treat patients with respiratory infectious diseases.Methods A negative pressure chamber with standard container sizes was developed whose enclosure structure involved in 2 mm-thick galvanized steel plate,10 mm-thick high-performance thermal isolation polyurethane foam board,2 mm-thick galvanized steel plate and 10 mm-thick integral inner panel.There were three functional areas included in the chamber for clean office area,semi-polluted passage and polluted ward with toilet.Negative pressure differences between the functional areas were generated by full DC air supply and exhaust system to form directional air flow in the chamber.The patient's exhaled air was purified before emission with the high-efficiency particulate air filtration system.The negative pressure chamber was equipped with a portable life monitoring and support device,a remote consultation and guidance system,a water and electricity support system and etc.Results Air quality tests showed that the negative pressure chamber met the national standards in air cleanliness,static pressure difference,number of dust particles,settled bacteria,microorganisms on the surface of the object and etc.Conclusion The negative pressure chamber compatible with kinds of carriers can be used for the isolation and emergency treatment of patients with respiratory infectious diseases and the long-distance transport of critically ill patients.[Chinese Medical Equipment Journal,2023,44(9):24-28]

Background: and Purpose Orthostatic hypotension (OH) is common in patients with Parkinson’s disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD. Methods: This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET).According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively. Results: CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (p<0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH (p<0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649–0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively. Conclusions This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.