Role of inhibiting lncRNA TUG1 to down⁃regulate nucleotide binding oligomerization domain like receptor protein 1 inflammasome in delaying the progression of Alzheimer’s disease / 解剖学报

Objective To investigate the relieving effects of knockdown of long non-coding RNA(lncRNA)taurine up-regulated gene 1 (TUG1) on inhibiting nucleotide binding oligomerization domain like receptor protein 1 (NLRP1) inflammasome and the progression of Alzheimer’ s disease. Methods Wild-type (WT group, 10 mice) or amyloid precursor protein (APP) / presenilin-1 (PS1) transgenic mice (30 mice) with a genetic background of C57 / BL6 aged 9-10 weeks were used in this study. APP / PS1 transgenic mice were randomly divided into model group, model+lncRNA TUG1 short hairpin RNA (shRNA) group and model + shRNA non target (NT) group (n = 10) . Blood samples, cerebral cortex tissues, primary microglial cells and primary astrocytes were collected from mice 12 weeks of age on day 1 (3-month-old) and 32 weeks of age on day 1 (8-month-old), with 5 mice per group at each time point. Real-time PCR analysis was used to detect the expression levels of lncRNA TUG1 and macrophage migration inhibitory factor (MIF) mRNA in cerebral cortex tissues and primary microglial cells, and C1r and C1s mRNA levels in primary astrocytes of 3-month-old and 8-month-old mice in the above 4 groups, respectively. ELISA was used to determine the MIF in plasma samples of the above 4 groups of mice. Primary microglia and astrocytes from the cerebral cortex of 3-month-old and 8-month-old mice were co-cultured. CCK-8 method was used to determine the proliferation ability of the above cells. Western blotting was used to determine the expression levels of MIF, pro interleukin-1β (pro-IL-1β), apoptosis associated speck-like protein containing a caspase recrult domain(ASC), Caspase-1 (p20), Caspase-1 (full), NLRP1 and NLRP3 in cerebral cortex tissues of 3-month-old and 8-month-old mice. Immunofluorescent staining was used to determine amyloid beta(Aβ) in cerebral cortex of 8-month-old mice. Results At the age of 3-month-old and 8-month-old, compared with the WT group, the relative expression level of lncRNA TUG1 and MIF in cerebral cortex tissues and primary microglia of model group mice was significantly up-regulated, with primary microglial cells and astrocytes proliferation ability enhanced (P0. 05) . There was no significant difference between the model group and the model+shRNA NT group mice of all the above factors (P>0. 05) . Conclusion In APP / PS1 transgenic mice, up-regulation of lncRNA TUG1 and MIF are positively associated with the activation of NLRP1 inflammasome in mice cerebral cortex tissues and primary microglia. Knock-down of lncRNA TUG1 can ameliorate the progression of Alzheimer’ s disease.

Advances in relationship between pyroptosis and pulmonary arterial hypertension and therapeutic drugs / 中国药理学通报

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Very-long chain acyl-coA dehydrogenase deficiency: report of a Chinese pedigree and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).@*METHODS@#A Chinese pedigree affected with VLCADD admitted at the First People's Hospital of Yunnan Province in February 2019 was selected as the study subject. The characteristics of disease onset, diagnosis and treatment and prognosis were retrospectively analyzed. Relevant literature was also systematically searched and reviewed.@*RESULTS@#The proband, a 1-year-old boy, had the clinical manifestations of frequently vomiting, hypoglycemia, abnormal liver function and myocardial enzymes. Tandem mass spectrometry screening showed significantly elevated C14, C14:1, C16:1, C16:2, C18 and C14/C8. Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene, namely c.664G>A (p.G222R) and c.1345G>A (p.E449K), which were respectively derived from his father and mother. The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later. Literature review has identified 60 Chinese children with VLCADD. The clinical classifications were mainly cardiomyopathy type and liver disease type, which accounted for 73.3% (43/60). The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD. Children with one or two loss-of-function (LOF) mutations showed more severe clinical manifestation and a higher mortality. Cardiomyopathy type had the poorest prognosis, with a mortality rate of 76.9% (20/26). C14:1 may be used as an indicator for the diagnosis of VLCADD, but cannot be used for clinical subtyping and prognosis evaluation. The c.1349G>A (p.R450H) variant had the highest frequency among the Chinese patients, accounting for 10.8% (13/120).@*CONCLUSION@#The clinical classifications of VLCADD are strongly correlated with the prognosis, and LOF mutations are more common in those with severe clinical manifestations. c.1349G>A (p.R450H) may be the most common variant among the Chinese patients, and early screening and diagnosis can greatly improve the prognosis of patients.

Observation on the efficacy of vedolizumab in the treatment of patients with active Crohn′s disease / 中华消化杂志

Objective:To preliminary observe the clinical efficacy of vedolizumab (VDZ) in the treatment of active Crohn′s disease (CD).Methods:From March 2021 to October 2022, a total of 22 patients with active CD who received VDZ treatment at Zhongda Hospital, Southeast University were retrospectively enrolled. The general clinical data, laboratory indicators, imaging finding and endoscopic images of the patients were collected. The Crohn′s disease activity index (CDAI), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), clinical remission rate were evaluated at week 0, 2, 6 and 14 of VDZ administration. Meanwhile, the response rate under endoscopy and remission rate under endoscopy were evaluated after 14 weeks of VDZ administration. The related factors affecting the efficacy of VDZ were further analyzed. Kruskal-Wallis H test and Mann-Whithey U test were used for statistical analysis. The multiple logistic regression analysis was used to find the related factors affecting the clinical remission after VDZ treatment. Results:The CDAI at week 0, 2, 6 and 14 after treatment were 181.01 (160.11, 231.56), 148.05 (134.88, 200.52), 127.46 (91.44, 163.62), and 82.35 (63.50, 121.84), respectively, and the differences were statistically significant ( H=34.23, P<0.001); there were statistically significant differences between week 0 and week 2, 6, 14 after treatment ( U=130.00, 80.00, 33.00; P=0.017, <0.001, and<0.001). The hs-CRP levels were 5.72 mg/L (3.59 mg/L, 11.10 mg/L), 2.86 mg/L (0.86 mg/L, 5.27 mg/L), 1.55 mg/L (0.86 mg/L, 9.89 mg/L) and 2.86 mg/L (0.86 mg/L, 3.12 mg/L), respectively, and the differences were statistically significant ( H=9.69, P=0.021); there were statistically significant differences between week 0 and week 2, 6, 14 after treatment ( U=102.00, 109.00, 98.00; P=0.026, 0.045, and 0.011) .The level of ESR after 14 weeks of VDZ treatment was 8.00 mm/1 h (4.00 mm/1 h, 17.00 mm/1 h), which significantly decreased compared with that before treatment (17.00 mm/1 h(12.25 mm/1 h, 21.75 mm/1 h)), and the difference was statistically significant ( U=132.50, P=0.020). The clinical remission rates at week 2, 6 and 14 after VDZ treatment were 54.5% (12/22), 68.2% (15/22) and 86.4% (21/22), respectively, and the clinical response rates were 18.2% (4/22), 54.5% (12/22) and 95.5% (21/22), respectively. After 14 weeks of VDZ treatment, among 17 patients who underwent endoscopic re-examination, 9 patients achieved response under endoscopy and 3 patients achieved remission under endoscopy. Stenotic type and penetrating type of CD, previous use of glucocorticoids or immunosuppressants were risk factors of no clinical remission after VDZ treatment ( β=-4.586, -5.005 and -3.371; OR=0.010, 0.007 and 0.034; P=0.010, 0.025 and 0.045). While VDZ treatment for 14 weeks was a protective factor ( β=2.475, OR=11.885, P=0.011). Conclusions:VDZ can effectively relieve disease activity in patients with active CD. The disease behavior of CD, previous medication treatment of patients, and the duration of VDZ treatment may be related to the efficacy of VDZ.

Case analysis of multiple endocrine adverse reactions associated with immune checkpoint inhibitors / 中华内分泌代谢杂志

Objective:To investigate the clinical features of multiple endocrine gland dysfunction in patients with tumors after using immune checkpoint inhibitors(ICIs).Methods:Cases with two or more abnormalities of endocrine gland function after immunotherapy were collected from the Department of Endocrinology, Zhongshan Hospital, Fudan University between January 2019 and January 2022. Clinical manifestations, laboratory tests, imaging, treatment and prognosis were analyzed.Results:A total of 12 patients were included, 6 males and 6 females, aged(61.2±10.0) years old. All patients received programmed cell death protein-1(PD-1) monoclonal antibody therapy, and the time to endocrine abnormality ranged from 9 to 94 weeks after administration. All patients developed primary hypothyroidism, 11 of them had isolated adrenocorticotropic hormone deficiency, and 1 had primary adrenal insufficiency.Conclusion:ICIs can involve multiple endocrine glands simultaneously or successively, mainly manifested as primary hypothyroidism and isolated adrenocorticotropic hormone deficiency. It is essential to assess the function of the pituitary and target glands in patients treated with ICIs to improve the safety of immunotherapy.

Changing trends of the clinical and epidemiological characteristics of acquired immunodeficiency syndrome-associated talaromycosis in Shanghai City / 中华传染病杂志

Objective:To analyze the clinical and epidemiological characteristics and changing trends of acquired immunodeficiency syndrome (AIDS)-associated talaromycosis in Shanghai City.Methods:The clinical data of patients with AIDS-associated talaromycosis hospitalized at Shanghai Public Health Clinical Center, Fudan University from Janauary 1, 2014 to December 31, 2021 were collected. The medical information included age, gender, place of origin, clinical symptoms, imaging manifestations, blood routine test, CD4 + T lymphocyte count. The chi-square test or Fisher exact probability test was used for statistical analysis. Univariate logistic regression was used to analyze the related risk factors for death. Results:From 2014 to 2021, a total of 12 165 AIDS patients were admitted, including 169 (1.4%) AIDS-assiociated talaromycosis patients. The proportions of AIDS-associated talaromycosis in AIDS inpatients from 2014 to 2021 were 1.8%(21/1 149), 1.1%(14/1 307), 1.3%(19/1 446), 0.9%(15/1 610), 1.2%(20/1 626), 1.2%(22/1 778), 1.7%(28/1 624) and 1.8%(30/1 625), respectively, which had not changed much. There was no statistically significant difference in the proportion of AIDS-associated talaromycosis in AIDS inpatients in different years ( χ2=9.50, P=0.218). Among the 169 patients, 157 cases (92.9%) were male, with the age of (37.9±12.2) years, and 35 were from Jiangxi Province, 31 from Shanghai Municipality, 29 from Zhejiang Province, 17 from Anhui Province, 14 from Fujian Province, 11 from Jiangsu Province, eight from Hunan Province, four from Heilongjiang Province, three cases each from Guangxi Zhuang Autonomous Region, Guizhou Province and Henan Province, two cases each from Hubei Province, Shandong Province, Shanxi Province, Yunnan Province and Guangdong Province, and one case from Chongqing Municipality. Patients from non-traditional endemic areas did not find a clear history of living in traditional endemic areas. Of 169 patients, 143(84.6%) cases had fever, 73(43.2%) had respiratory symptoms, and 26(15.4%) had rash during the course of the disease, 147(87.0%) had pulmonary imaging abnormalities, 94(55.6%) were complicated by other pathogens, and 44(26.0%) had hepatosplenomegaly, 137(81.1%) had CD4 + T lymphocyte count <50/μL. Twenty-three patients died, with the total fatality rate of 13.6%. The overall mortality rate showed a downward trend year by year. There was a statistically significant difference in the case fatality rate of AIDS-associated talaromycosis in different years (Fisher exact probability test, P=0.046). The result of univariate logistic regression model showed that patients with platelet count<50×10 9/L had an increased risk of death (odds ratio ( OR)=3.33, 95% confidence interval ( CI) 1.13 to 9.81, P=0.029). Conclusions:The overall change of AIDS-associated talaromycosis inpatients in Shanghai is not significant, while the prevalence rate has increased slightly in recent two years. The case fatality rate is declining year by year. The proportions of patients without a history of living in or traveling to epidemic areas and without rash as the first manifestation are high, and the main clinical manifestation is multi-system damage. Patients with platelet count<50×10 9/L have an increased risk of death.

Investigation on the incidence of IRIS in HIV patients with TB infection and its relationship with Th17/Treg, CD4 + T lymphocyte levels / 中国医师杂志

Objective:To investigate the incidence of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV (HIV) and tuberculosis (TB) infection, and analyze the relationship between Th17/Treg cytokines, CD4 + T lymphocytes and IRIS. Methods:HIV patients with TB infection admitted to Public Health Clinical Center of Chengdu from June 2020 to June 2022 were divided into IRIS group (31 cases) and non IRIS group (93 cases) according to whether IRIS occurred after highly active antiretroviral therapy (HAART). The Demography data, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was conducted to investigate the influencing factors of IRIS in HIV patients with TB infection.Results:There was no significant difference in Demography data between the two groups ( P>0.05). There was a statistically significant difference in the history of opportunistic infection between the IRIS group and the non IRIS group (χ 2=5.194, P<0.05). The levels of HIV RNA, interleukin (IL)-17, and IL-23 in the IRIS group were higher than those in the non IRIS group (all P<0.05). The levels of the γ interferon (IFN- γ), the transforming growth factor-β (TGF- β) and baseline CD4 + T lymphocyte count were lower than those in the non IRIS group (all P<0.05). The results of multivariate logistic regression analysis showed that IL-17 ( OR: 1.266, 95% CI: 1.095-1.464), IL-23( OR: 1.384, 95% CI: 1.120-1.710), and TGF- β( OR: 0.589, 95% CI: 0.436-0.797) were influencing factors for the occurrence of IRIS in HIV patients with TB infection (all P<0.05). Conclusions:For patients with high IL-17 levels, high IL-23 levels, and low TGF- β level of HIV complicated with TB infection, clinical prevention and control should be carried out as soon as possible to prevent the occurrence of IRIS.

Longitudinal study on the track of postoperative supportive care needs and influencing factors in patients with non-small cell lung cancer / 中国实用护理杂志

Objective:To explore the potential categories of post-operative supportive care demand trajectory for patients with non-small cell lung cancer (NSCLC), analyze the influencing factors, and propose targeted interventions.Methods:This was a prospective observational study. A convenient sampling method was used to select 177 NSCLC patients who received surgical treatment in Shanghai Lung Hospital Affiliated to Tongji University from January 2021 to February 2022. The Supportive Care Demand Scale for cancer patients was used to investigate the level of patients′supportive care demand 1 day before operation, 3 days after operation, 1 day before discharge, 1 week after discharge, 1 month after discharge, and 3 months after discharge, and the potential growth model was used to identify the trajectory category and multi category Logistic regression analysis was used to explore the influencing factors.Results:Three supportive care demand trajectories were fitted out in this study, which were the continuous high demand group (46.33%), the slowly decreasing demand group (30.51%), and the low decreasing demand group (23.16%). With the potential category group 3, low demand reduction group as the reference category, Logistic regression analysis showed that high psychological distress, low social support, high disease stage, high comorbidities were more likely to enter the continuous high demand group ( OR = 0.826 to 18.526, all P<0.05), and high education level (college education and above and high school) were more likely to enter the slowly decreasing demand group ( OR = 6.076, 4.199, both P<0.05). Conclusions:The demand track of NSCLC patients for supportive care after surgery has population heterogeneity. Clinical medical staff should provide personalized social support and emotional support for patients with high disease stage, more complications and low education level in the early postoperative period.

The specific outcome Assessment Modal of acupuncture and Tuina treatment for pain / 国际中医中药杂志

Acupuncture and Tuina are the main non-drug therapies for low back pain, which are recommended by the guidelines. Acupuncture and Tuina can alleviate pain, which is regarded as conditional specific outcome, and improve mental, emotional problems, as non-conditional specific outcomes. There are some problems of the outcome assessment of acupuncture and Tuina treatment for pain such as insufficient evaluation of specific effect and unclear evaluation of characteristic outcome. Therefore, the key to above problems is to construct a Specific ouTcomE Assessment Modal of acupuncture and Tuina treatment for pain (STEAM-A&T) based on the qualitive and quantitative methods. By describing the experience, narrative expression, feelings and needs of patients who receiving acupuncture and Tuina treatment, the item banks of acupuncture and Tuina treatment effect are constructed, and the characteristic outcome of acupuncture and Tuina for pain will be screened, and then the relationship model among outcomes is constructed and optimized, which reflected the characteristics of acupuncture and Tuina for pain from multiple dimensions, multiple levels and multiple views. We reveal the relationship between the outcome of acupuncture and Tuina for pain. It will provide a new theory and methods for the construction of specific outcome assessment modal of Traditional Chinese Medicine.

Advances in the treatment of extramammary Paget disease / 国际肿瘤学杂志

Extramammary Paget disease (EMPD) is a kind of rare clinical malignant tumor in the skin. Surgical treatment is the main treatment method, and the Mohs microsurgery is considered the first choice which can control the incision margin accurately and reduce the recurrence rate. Due to the insidious and multifocal nature of the disease, the postoperative recurrence rate is still high. The other treatment methods include radiation therapy, chemotherapy, targeted therapy, photodynamic therapy, local drug therapy and laser therapy. Further research on the progress of EMPD treatment is helpful for the management and treatment of patients in clinical practice.

Research progress on targeted therapy of breast cancer with low expression of HER2 / 国际肿瘤学杂志

Breast cancer has become the malignant tumor with the highest incidence rate among women, of which human epidermal growth factor receptor 2 (HER2) positive breast cancer accounts for about 15%-20%. With the development of anti HER2 targeted drugs, the survival and prognosis of HER2 positive breast cancer has significantly benefited. About 45%-55% of breast cancer patients have low HER2 expression, and these patients usually do not receive anti HER2 treatment. However, there is a significant difference between the biological behavior and prognosis of breast cancer with low HER2 expression and breast cancer with zero HER2 expression. It is helpful to differentiate and adopt corresponding treatment strategies to improve the prognosis of patients. At present, there have been many advances in targeted therapy of breast cancer with low HER2 expression, which provides a useful reference for precision treatment of breast cancer with low HER2 expression.

Study on pharmaceutical care model for drug-related problems in elderly patients based on comprehensive medication management review / 中国药房

OBJECTIVE To explore the pharmaceutical care model for elderly patients with drug-related problems （DRPs） based on the comprehensive medication management review （CMMR）， and to observe the effect of pharmaceutical care under the model. METHODS The pharmaceutical care new model for elderly patients was established by concerning CMMR guidelines in Australia. In other words， clinical pharmacists receive medical care through referral by health practitioners and active consultation by patients or their caregivers. Visits were made by a combination of face-to-face and telephone interviews. Follow-up was carried out in the form of outpatient follow-up， telephone follow-up， appointment， and home guidance to know about the treatment of DRPs by healthcare practitioners or patients.Under this model， the occurrence status and classification of DRPs in elderly patients were studied through cross-sectional investigation. The effect of pharmaceutical care was evaluated from the aspects of hospitalization rate， adverse drug reaction （ADR） incidence，medication compliance， the number of medications， blood lipid level， etc.， through self-before-after comparison. RESULTS In this study， a patient-centered， evaluation-intervention-reevaluation closed-loop pharmaceutical care model was formed. Among 317 study subjects， the average number of DRPs was 1.03 （0-7） cases. Compared before and after the intervention， the number of drug types increased from 2.00（0.00，3.00） to 2.00（1.00，3.00）， but the level of low-density lipoprotein cholesterin in patients decreased from 3.48 （2.58， 4.29） mmol/L to 3.11 （2.29，3.81） mmol/L （P＜0.05）. There was no statistical significance in hospitalization rate， ADR incidence within or medication compliance. CONCLUSIONS CMMR-based pharmaceutical care model can effectively identify and manage the patients’ DRPs and reduce the level of blood lipid.

Portal vein aneurysm after liver transplantation: report of two cases and literature review / 器官移植

Objective To summarize the diagnosis and treatment experience of portal vein aneurysm after liver transplantation. Methods Clinical data of two recipients with portal vein aneurysm after liver transplantation were retrospectively analyzed. Clinical features, diagnosis, treatment and prognosis were summarized based on literature review. Results Both two cases were diagnosed with intrahepatic portal vein aneurysm complicated with portal vein thrombosis and portal hypertension after liver transplantation. Case 1 was given with targeted conservative treatment and he refused to undergo liver retransplantation. Physical condition was worsened after discharge, and the patient eventually died from liver graft failure, kidney failure, lung infection, and septic shock. Case 2 received high-dose glucocorticoid pulse therapy, whereas liver function was not improved, and the patient was recovered successfully after secondary liver transplantation. Conclusions Long-term complication of portal vein aneurysm (especially intrahepatic type) after liver transplantation probably indicates poor prognosis. Correct understanding, intimate follow-up and active treatment should be conducted. Liver retransplantation may be a potential treatment regimen.

Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy and adverse reactions of peginterferon-α2b for treatment of chronic myeloproliferative neoplasms (MPN).@*METHODS@#We retrospectively analyzed the data of 107 patients with MPN, including 95 with essential thrombocythemia (ET) and 12 with polycythemia vera (PV), who all received peginterferon-α2b treatment for at least 12 months. The clnical and follow-up data of the patients were analyzed to evaluate the efficacy and adverse reactions of the treatment.@*RESULTS@#After receiving peginterferon- α2b treatment, both ET and PV patients achieved high hematological remission rates, and the total remission rates did not differ significantly between the two groups (86% vs 78%, P>0.05). In the overall patients, the spleen index decreased by 13.5% (95%CI: 8.5%-18.5%) after the treatment. The patients with hematological remission showed a significantly greater reduction of the total symptom score than those without hematological remission (P < 0.01). The median percentage of JAK2V617F allele load of PV patients decreased from 67.23% (49.6%-84.86%) at baseline to 19.7% (0.57%-74.6%) after the treatment, and that of JAK2V617F-positive ET patients decreased from 48.97% (0.45%-74.24%) at baseline to 22.1% (0.33%-65.42%) after the treatment. Mild adverse reactions (grade 1-2) were observed in both ET and PV groups without significant differences between them. The overall incidence of thrombotic events during the treatment was 2.8% in these patients, and no serious adverse reactions were observed.@*CONCLUSION@#For patients with chronic myelodysplasia, peginterferon-α2b treatment can achieve a high peripheral blood cell remission rate and maintain a long-term stable state with good effect in relieving symptoms such as splenomegaly. Peginterferon- α2b treatment caused only mild adverse reactions, which can be tolerated by most of the patients.

Innovation,thinking and prospect of benign prostatic hyperplasia surgery / 现代泌尿外科杂志

Benign prostatic hyperplasia (BPH) surgery has developed for more than 100 years. After several major revolutions, it is still constantly innovating, which in turn has profoundly affected people’s concept and strategy for treating BPH. This paper reviews the background and process of the evolution of BPH surgery, discusses the innovative methods and rules, and looks forward to the future developmental trend, in order to provide reference for the further development of BPH surgery.

Efficacy and safety of domestic Paliperidone extended-release tablets in the treatment of stable schizophrenia / 中国药房

OBJECTIVE To investigate the efficacy and safety of domestic Paliperidone extended-release tablets as a substitute for original Paliperidone extended-release tablets in the treatment of stable schizophrenia. METHODS A total of 65 patients with schizophrenia， who were treated with single original Paliperidone extended-release release tablets for 2 months or more in the outpatient or inpatient department of Shandong Daizhuang Hospital from June 2021 to June 2022， were collected and randomly divided into the domestic group （33 cases） and the original group （32 cases）. The domestic group was treated with the same dose of domestic Paliperidone extended-release tablets instead for 2 months， and the original group continued to use the previous dose of the original drug for 2 months. Positive and negative syndrome scale （PANSS） and treatment emergent symptom scale （TESS） were used to evaluate the two groups at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment. The incidence of ADR was calculated at the end of 2 months after enrollment. The fasting blood glucose， blood lipid indicators （triglyceride， total cholesterol， low-density lipoprotein， high-density lipoprotein， very-low-density lipoprotein）， serum prolactin levels， and paliperidone blood concentration were determined after the intravenous blood sample was collected. The ratio of paliperidone blood concentration to dose （C/D value） was calculated， and an electrocardiogram was performed. RESULTS There were 31 and 30 patients in the domestic group and the original group who completed the trial， respectively. There were no statistical significances in PANSS score， TESS score or C/D value at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment； there were no statistical significances in the levels of fasting blood glucose， blood lipid or serum prolactin at the time of enrollment and at the end of 2 months after enrollment （P＞0.05）. PANSS scores of both groups significantly decreased at the end of 1 month and 2 months after enrollment （P＜0.01）. The incidences of ADR were 25.81% in the domestic group and 30.00% in the original group， without significant difference （P＞0.05）， and there were no significant abnormalities in the electrocardiograms of the two groups. CONCLUSIONS Domestic Paliperidone extended-release tablets can directly replace the original tablets in the treatment of stable schizophrenia， and their clinical efficacy and safety are comparable.

Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis

Objective@#Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk. @*Methods@#This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate. @*Results@#With adjustment for age, a three-class model was identified, with 42.7% of participants classified as “low comorbidity class (cluster 1)”, 44.2% as “cardiometabolic multimorbidity class (cluster 2)”, and 13.1% as “FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract).” The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708–14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281–1.953; p<0.001) in cluster 3. @*Conclusion@#Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.

Inflammatory Bowel Disease and Neurodegenerative Diseases

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.

Method of transfection of STOP gene lentiviral vector into oligodendrocyte precursor cells of BTBR mouse model of autism / 解剖学报

Objective To investigate the effect of microtubule binding protein STOP on myelin formation of oligodendrocyte in BTBR mice spectrum disorder in vitro, a highly purified primary culture method of oligodendrocyte precursor cells from cerebral cortex of BTBR mice was established. Establishment of a highly efficient transfection method for overexpression of STOP gene in oligodendrocyte precursor cells of BTBR mice cerebral cortex using lentiviral vector. Methods BTBR mice were used as experimental objects, 6-10 suckling mice were taken each time, repeat 3 times independently. The single cell suspension was prepared by trypsin digestion, and the primary oligodendrocyte precursor cells were obtained by immunomagnetic bead cell sorting method . After 5 days of culture, the cell purity was identified by oligodendrocyte precursor cell marker staining. The primary cultured oligodendrocyte precursor cells were transfected with STOP gene vector constructed in the early stage of the project group. 72-96 hours after transfection, the fluorescence staining of oligodendrocyte precursor cells was observed under fluorescence microscope, and the transfection rate and cell survival rate were calculated. Results The oligodendrocyte precursor cells of BTBR mice extracted by immunomagnetic beads sorting method basically adhered to the wall completely after 48 hours, and the cells had strong ability of proliferation. On the fifth da)' of culture, the purity of the cells was more than 95% identified by immunofluorescence. A lentivirus transfection method for primary oligodendrocyte precursor cells of BTBR mice with high transfection efficiency was established. The fluorescence expression of the cells was obvious after being photographed by high connotation microscope, the lentivirus transfection rate of oligodendrocyte precursor cells was increased to 60%-70%. Conclusion The primaiy oligodendrocyte precursor cells of BTBR mouse cerebral cortex with high purity were successfull)' isolated and cultured. A method for lentivirus infection of primaiy oligodendrocyte precursor cells in the cerebral cortex of BTBR mice is successfully established.