Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus.

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.

Timing of stage Ⅱ vitrectomy in patients with open ocular trauma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the clinical efficacy of vitrectomy at different times for open ocular trauma and explore the timing of stage Ⅱ vitrectomy.METHODS: Retrospective case series study. A total of 60 cases(60 eyes)with open ocular trauma who visited our ophthalmology department from June 2022 to February 2023 were included. They were divided into treatment group A(interval ≤14 d)and treatment group B(interval >14 d)based on the interval between the stage Ⅰ emergency treatment surgery and the stage Ⅱ vitreoretinal surgery. Among the 32 cases(32 eyes)in the treatment group A, 16 eyes(50%)had eyeball rupture, 13 eyes(41%)had penetrating injury, and 3 eyes(9%)had perforating injury. Among the 28 cases(28 eyes)in the treatment group B, 15 eyes(54%)had eyeball rupture, 12 eyes(43%)had penetrating injury, and one eye(4%)had perforating injury. The two groups of patients were followed-up for 6 mo after surgery, and the treatment effects were compared.RESULTS:There was no statistically significant difference in visual acuity between the two groups of patients before vitrectomy(P>0.05). In the treatment group A, 10 eyes(31%)had significantly improved visual acuity, 21 eyes(66%)had effectively enhanced visual acuity, and 1 eye(3%)had no improvement in visual acuity at 6 mo after surgery. Among the 28 eyes in the treatment group B, 5 eyes(18%)had significantly improved vision, 16 eyes(57%)had effectively enhanced vision, and 7 eyes(25%)had no change in vision, with statistically significant difference between the two groups(U=322.5, P=0.032). There was no significant difference between the treatment group A and the treatment group B in complications such as secondary glaucoma, silicone oil dependence, vitreous hemorrhage, and eyeball atrophy(P>0.05). There was no evidence of traumatic proliferative vitreoretinopathy(TPVR)in the treatment group A during postoperative follow-up, which was significantly lower than that of the treatment group B(P<0.05).CONCLUSION:The prognosis of the stage Ⅱ vitrectomy for open ocular injury is relatively good after completing the stage Ⅰ surgery within 2 wk.

Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition.

Podocyte injury plays a critical role in the progression of focal segmental glomerulosclerosis (FSGS). Here, it is reported that B-cell translocation gene 2 (Btg2) promotes Adriamycin (ADR)-induced FSGS via Smad3-dependent podocyte-mesenchymal transition. It is found that in FSGS patients and animal models, Btg2 is markedly upregulated by podocytes and correlated with progressive renal injury. Podocyte-specific deletion of Btg2 protected against the onset of proteinuria and glomerulosclerosis in ADR-treated mice along with inhibition of EMT markers such as α-SMA and vimentin while restoring epithelial marker E-cadherin. In cultured MPC5 podocytes, overexpression of Btg2 largely promoted ADR and TGF-ß1-induced EMT and fibrosis, which is further enhanced by overexpressing Btg2 but blocked by disrupting Btg2. Mechanistically, Btg2 is rapidly induced by TGF-ß1 and then bound Smad3 but not Smad2 to promote Smad3 signaling and podocyte EMT, which is again exacerbated by overexpressing Btg2 but blocked by deleting Btg2 in MPC5 podocytes. Interestingly, blockade of Smad3 signaling with a Smad3 inhibitor SIS3 is also capable of inhibiting Btg2 expression and Btg2-mediated podocyte EMT, revealing a TGF-ß/Smad3-Btg2 circuit mechanism in Btg2-mediated podocyte injury in FSGS. In conclusion, Btg2 is pathogenic in FSGS and promotes podocyte injury via a Smad3-dependent EMT pathway.

Research Advances on Childhood and Adolescent Vaccinations and Seizures / 中山大学学报(医学科学版)

Vaccination for children and adolescents is an effective strategy for preventing and controlling infectious diseases. However， clinical reports showed that vaccination may be associated with epilepsy or seizures， potentially increasing public hesitancy about vaccination， and affecting vaccination coverage. At present， no evidence showed that vaccination could damage the nervous system and cause epilepsy or seizures. In this review， we explore the association of multiple vaccinations in children and adolescents with epilepsy or seizures， and further understand the safety of vaccination， thereby improving vaccine coverage in China.

Type III secretory protein SINC of Chlamydia psittaci promotes host cell autophagy by activating the MAPK/ERK signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of SINC, a secreted protein of Chlamydia psittaci, on autophagy of host cells and the role of MAPK/ERK signaling pathway in mediating SINC-induced autophagy.@*METHODS@#RAW 264.7 cells treated with recombinant SINC were examined for changes in expression levels of LC3-II, Beclin-1, phosphorylated and total ERK1/2 using Western blotting. The expression level of LC3 in the treated cells was detected using immunofluorescence analysis, and the formation of autophagosomes and autolysosomes was observed with transmission electron microscopy (TEM). The effect of pretreatment with U0126 (a specific ERK inhibitor) on the expression levels of LC3-II and Beclin-1 in RAW 264.7 cells exposed to different concentrations of SINC was examined using Western blotting, and LC3 puncta in the cells was detected with immunofluorescence analysis.@*RESULTS@#The expression levels of LC3-II and Beclin-1 were the highest in RAW 264.7 cells treated with 2 μg/mL SINC for 12h. Immunofluorescence analysis showed exposure to SINC significantly increased the number of cells containing LC3 puncta, where the presence of autophagosomes and autolysosomes was detected. Exposure to 2 μg/mL SINC for 15 min resulted in the most significant increase of the ratios of p-ERK1/2/ERK1/2 in RAW 264.7 cells. Pretreatment of the cells with U0126 prior to SINC exposure significantly decreased the ratio of p-ERK1/2/ERK1/2, lowered the expression levels of LC3-II and Beclin-1, and decreased LC3 aggregation in the cells.@*CONCLUSIONS@#SINC exposure can induce autophagy in RAW 264.7 cells by activating the MAPK/ERK signaling pathway.

Prognostic value of serum sodium variability within 72 hours and lactic acid combined with severity score in patients with sepsis / 中华危重病急救医学

OBJECTIVE@#To explore the predictive value of serum sodium variability within 72 hours, lactic acid (Lac), sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) in predicting the 28-day prognosis of sepsis patients.@*METHODS@#The clinical data of patients with sepsis admitted to the department of intensive care unit (ICU) of the Affiliated Qingdao Municipal Hospital of Qingdao University from December 2020 to December 2021 were retrospectively analyzed, including age, gender, previous medical history, temperature, heart rate, respiratory rate, systolic pressure, diastolic pressure, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), C-reactive protein (CRP), pH value, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), Lac, prothrombin time (PT), activated partial thromboplastin time (APTT), serum creatinine (SCr), total bilirubin (TBil), albumin (Alb), SOFA, APACHE II score, and 28-day prognosis. Multivariate Logistic regression was used to analyze the risk factors of death in sepsis patients. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of serum sodium variability within 72 hours, Lac, SOFA, APACHE II alone and in combination on the prognosis of patients with sepsis.@*RESULTS@#A total of 135 patients with sepsis were included, 73 survived and 62 died at 28 days, with 28-day mortality of 45.93%. (1) Compared with the survival group, SOFA, APACHE II, Lac and serum sodium variability within 72 hours in the death group were significantly higher [SOFA: 10.00 (8.00, 12.00) vs. 6.00 (5.00, 8.00), APACHE II: 18.00 (16.00, 21.25) vs. 13.00 (11.00, 15.00), Lac (mmol/L): 3.55 (2.90, 4.60) vs. 2.00 (1.30, 2.80), serum sodium variability within 72 hours: 3.4% (2.6%, 4.2%) vs. 1.4% (1.1%, 2.5%)], the differences were statistically significant (all P < 0.01). (2) Multivariate Logistic regression showed that SOFA, APACHE II, Lac, serum sodium variability within 72 hours were independent risk factors of prognosis in patients with sepsis [SOFA: odds ratio (OR) = 1.479, 95% confidence interval (95%CI) was 1.114-1.963, P = 0.007; APACHE II: OR = 1.163, 95%CI was 1.009-1.340, P = 0.037; Lac: OR = 1.387, 95%CI was 1.014-1.896, P = 0.040; serum sodium variability within 72 hours: OR = 1.634, 95%CI was 1.102-2.423, P = 0.015]. (3) ROC curve analysis showed that SOFA, APACHE II, Lac and serum sodium variability within 72 hours had certain predictive value for the prognosis of sepsis patients [SOFA: the area under the ROC curve (AUC) = 0.858, 95%CI was 0.795-0.920, P = 0.000; APACHE II: AUC = 0.845, 95%CI was 0.776-0.913, P = 0.000; Lac: AUC = 0.840, 95%CI was 0.770-0.909, P = 0.000; serum sodium variability within 72 hours: AUC = 0.842, 95%CI was 0.774-0.910, P = 0.000]. The combined predictive value of the four indicators (AUC = 0.917, 95%CI was 0.870-0.965, P = 0.000) was higher than that of any single indicator, and has higher specificity (79.5%) and sensitivity (93.5%), indicating that the combined index has higher predictive value for the prognosis of sepsis patients than any single index.@*CONCLUSIONS@#SOFA, APACHE II, Lac, serum sodium variability within 72 hours are independent risk factors for 28-day death in patients with sepsis. The combination of SOFA score, APACHE II score, Lac and serum sodium variability within 72 hours has higher predictive value for prognosis than single index.

Value of the expression levels of complement-3a receptor 1 and neutrophil extracellular traps in predicting sepsis-induced coagulopathy / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical value of complement-3a receptor 1 (C3aR1) and neutrophil extracellular traps (NETs) in predicting sepsis-induced coagulopathy (SIC).@*METHODS@#A prospective study was conducted among 78 children with sepsis who attended Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from June 2022 to June 2023. According to the presence or absence of SIC, they were divided into two groups: SIC (n=36) and non-SIC (n=42) . The two groups were compared in terms of clinical data and the levels of C3aR1 and NETs. The factors associated with the occurrence of SIC were analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the performance of C3aR1 and NETs in predicting SIC.@*RESULTS@#Compared with the non-SIC group, the SIC group had significantly higher levels of C-reactive protein, interleukin-6 (IL-6), interleukin-10, C3aR1, and NETs (P<0.05). The multivaiate logistic regression analysis showed that the increases in C3aR1, NETs, and IL-6 were closely associated with the occurrence of SIC (P<0.05). The ROC curve analysis showed that C3aR1 combined with NETs had an area under the curve (AUC) of 0.913 in predicting SIC (P<0.05), which was significantly higher than the AUC of C3aR1 or IL-6 (P<0.05), while there was no significant difference in AUC between C3aR1 combined with NETs and NETs alone (P>0.05).@*CONCLUSIONS@#There are significant increases in the expression levels of C3aR1 and NETs in the peripheral blood of children with SIC, and the expression levels of C3aR1 and NETs have a high clinical value in predicting SIC.

Research Progress on the Influence of Bile Acids on the Immune Response of Hepatitis B Vaccine / 中山大学学报(医学科学版)

Hepatitis B vaccine （HepB） vaccination is the safest and most effective means of preventing hepatitis B virus （HBV） infection. HepB non-response is influenced by multiple factors， and solving the problem of poor immune response after HepB vaccination is of great significance for controlling HBV infection. Bile acids play an important role in human immune regulation， and whether bile acids have an effect on the HepB immune response has not been definitively studied. This article reviews the correlation between bile acids and HepB immune response， and provides a reference for further clarifying the pathogenesis and immunoprevention of bile acids in vaccine immunity.

Thirteen new peptaibols with antimicrobial activities from Trichoderma sp / 中国天然药物

From the fungus Trichoderma sp., we isolated seven novel 18-residue peptaibols, neoatroviridins E-K (1-7), and six new 14-residue peptaibols, harzianins NPDG J-O (8-13). Additionally, four previously characterized 18-residue peptaibols neoatroviridins A-D (14-17) were also identified. The structural configurations of the newly identified peptaibols (1-13) were determined by comprehensive nuclear magnetic resonance (NMR) and high-resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS/MS) data. Their absolute configurations were further determined using Marfey's method. Notably, compounds 12 and 13 represent the first 14-residue peptaibols containing an acidic amino acid residue. In antimicrobial assessments, all 18-residue peptaibols (1-7, 14-17) exhibited moderate inhibitory activities against Staphylococcus aureus 209P, with minimum inhibitory concentration (MIC) values ranging from 8-32 μg·mL-1. Moreover, compound 9 exhibited moderate inhibitory effect on Candida albicans FIM709, with a MIC value of 16 μg·mL-1.

GC-MS analysis and anti-inflammatory activity of low polarity parts from 3 species of Sabia genus / 中国药房

OBJECTIVE To investigate the component characteristics and anti-infla mmatory activities of the low polarity parts from Sabia campanulata ，S. discolor and S. parviflora . METHODS Gas chromatography-mass spectrometry was used to analyze the components of low polarity parts eluted by petroleum ether from petroleum ether extract of dried stems and leaves of S. campanulata，S. discolor and S. parviflora . The chromatographic peaks were retrieved by both NIST 17 and Wiley 275 database， and their structures of each compound were compared and identified manually. The relative percentage content of each component was calculated by peak area normalization method. With indomethacin as positive control and the inhibition rate of nitric oxide （NO）production as the index ，the effects of the low polarity parts of the above three species of Sabia genus on the production of NO in lipopolysaccharide-induced human rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） and mouse mononuclear macrophage RAW 264.7 were compared ；the half inhibitory concentration （IC50）was calculated. RESULTS Totally 70，40 and 33 chemical components were identified respectively from the low polarity parts of S. campanulata ，S. discolor and S. parviflora ， including long-chain fatty hydrocarbons ，long-chain alcohol/aldehyde/ester ，monoterpenes；but there were only 5 common components in the three species ，such as dodecane and docosane，etc. S. campanulata contained abundant terpenoids （40.89％）； the relative percentage content of triterpenoids was high in S. discolor （30.29％）；the relative percentage content of long-chain fatty hydrocarbons was high in S. parviflora （87.70％）. The values of IC 50 of the low polarity parts of the above three species of Sabia genus to the production of NO in RA-FLS cells were 2.22，1.69 and 4.15 μg/mL，respectively. The values of IC 50 of them to the production of NO in RAW 264.7 cells were 1.23，4.02 and 3.05 μg/mL respectively，and all of them were lower than indomethacin （12.97，10.66 μg/mL）. CONCLUSIONS The components of the low polarity parts fr om the above three species of Sabia genus are mainly long-chain fatty hydrocarbons ， monoterpenes and long-chain alcohol/aldehyde/ester ， and all of them have certain anti-inflammatory activities.

Multicenter retrospective study of 38 cases with fumarate hydratase deficiency uterine leiomyoma / 中华妇产科杂志

Objective:To investigate the clinicopathological features of fumarate hydratase (FH) deficiency uterine leiomyoma.Methods:The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed. The expressions of FH, S-(2-succino)-cysteine (2SC), desmin, p16, p53, CD 10 and cell proliferation associated nuclear antigen (Ki-67) proteins were detected by immunohistochemistry, and their clinicopathological features were analyzed retrospectively. Results:(1) Clinical features: the median age of the patients was (42.5±7.4) years old. Twenty-one cases (55%) of them were myomas found in physical examination, and the median maximum diameter of the tumor was 6.0 cm (range: 5.0-7.5 cm); myomectomy was performed in 23 cases (61%), total hysterectomy with or without bilateral appendages in 15 cases (39%); laparoscopic surgery in 27 cases (71%), open surgery in 11 cases (29%); none of the patients had renal cell carcinoma. (2) Histological features: atypical nuclear cells were distributed locally or diffusely, eosinophilic nucleoli and intranuclear inclusion bodies could be seen, glass like globules could be seen in the cytoplasm, nuclear division was 0-4/10 high power field (HPF), and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma. Among 38 patients with FH deficiency uterine leiomyoma, FH was negative in 37 cases (97%), and positive in 1 case (3%); 2SC, desmin, p16, p53, CD 10 and Ki-67 showed focal positive expression in 38 cases (100%), including 35 cases (92%) with Ki-67 index<10% and 3 cases (8%) with Ki-67 index ≥10%. (3) Follow-up: 4 cases (11%) recurred, and there was no death. There were significant differences in age, family history, distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group (all P<0.05). Conclusions:FH deficiency uterine leiomyoma is a rare tumor, which needs pathological examination,immunohistochemical examination and clinical history. Patients younger than 43 years old, with family history, histologically atypical diffuse nuclear distribution and mitotic number ≥3/10 HPF should be alert to the risk of recurrence.

Study on quality standard for Xuanxi Rongjin powder / 药学实践杂志

Objective To revise the qualitative and quantitative determination methods of Xuanxi Rongjin powder. Methods TLC was used to qualitatively identify Chuanxiong and Chuanshanlong. The content of cinnamaldehyde in the preparation was determined by HPLC with KR100-5C18 column (250 mm×4.6 mm, 5μm). The mobile phase was acetonitrile-water (35:65) and the detection wavelength was 290 nm. Results TLC can qualitatively identify Chuanxiong and Chuanshanlong. Cinnamaldehyde has a good linear relationship in the range of 0.0489~0.3260 µg/ml (r=1.00), The average recovery was 95.71% (RSD=1.78%). Conclusion The method has high sensitivity, good specificity, simple operation and good reproducibility.

Clinicopathologic features and prognosis of appendendicular goblet cell adenocarcinoma / 中华普通外科杂志

Objective:To investigate the clinicopathological characteristics, and prognosis of appendiceal goblet cell adenocarcinoma(GCA).Methods:The clinical and pathological data of 21 GCA cases were retrospectively analyzed, and their pathological morphology, immunohistochemical phenotype, genetic alteration and clinical treatment and prognosis were studied.Results:Most of the 21 patients showed appendicitis, with appendectomy alone or extensive resection of the tumor, followed by chemotherapy. There were 12 low-grade and 9 moderate and high-grade patients by pathological examination, and tumor cells express CEA, CK20, SATB-2, Syn(19/21), CgA(18/21), CD56(18/21), Ki67(+,10%-50%),and one patient had mutations in the BRAF gene.Depth of tumor infiltration ( r=0.716, P<0.001), and TNM stage ( r=0.816, P<0.001) were all positively correlated with the grade of GCA. After 19 to 98 months of follow-up, one patient relapsed and one patient died. Conclusions:Appendiceal GCA is a kind of tumor with bidirectional differentiation characteristics. Its morphology and biological behavior lineage are relatively broad, especially the high level is more aggressive, hence more active treatment should be adopted.

Study on quality standard of Jingtian Zhitong cream / 药学实践杂志

Objective To revise the determination method in the quality standard of Jingtian Zhitong cream. Methods The total saponins of angelica sinensis, Ligusticum wallichii, Rhizoma corydalis, and Panax notoginseng saponins were qualitatively identified by thin-layer chromatography (TLC). The contents of notoginsenoside R1, ginsenoside Rg1, and ginsenoside Rb1 in the preparation were determined by high performance liquid chromatography (HPLC). Results TLC showed strong specificity and good resolution. The concentration of notoginsenoside R1 showed a good linear relationship in the range of 0.1604 and 2.0050μg (r=0. 999). The concentration of ginsenoside Rg1 showed a good linear relationship in the range of 0.8003 and 10.0035μg (r=1.000). The concentration of ginsenoside Rb1 showed good linearity in the range of 0.6182 and 7.7275μg (r=1.000). The sample recovery rates were 101.43%, 98.75% and 100.95%, respectively. The relative standard deviation (RSD) were 2.56%, 2.71% and 2.75%, respectively. Conclusion The developed method is accurate and reliable with high sensitivity, which can be used for the quality control of Jingtian Zhitong cream.

Clinical Analysis of Gene Mutation and Vascular Events in Patients with BCR/ABL Negative Myeloproliferative Neoplasms / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between clinical features, peripheral blood cell count, coagulation function, gene mutation and hemorrhagic events and thrombotic events in essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis(PMF) patients.@*METHODS@#Clinical data of 78 patients with ET, PV, and PMF who were admitted to the Second Affiliated Hospital of Chongqing Medical University between September 2019 and August 2020 were retrospectively analyzed. Information about sex, age, gene mutation, peripheral blood cell count, coagulation function, and hemorrhagic and thrombotic events was included, and the influence of these data on the occurrence of hemorrhagic and thrombotic events was estimated.@*RESULTS@#Among the 78 patients with myeloproliferative neoplasms, there were 47 cases of ET, 15 cases of PV, and 16 cases of PMF.A total of 10 patients (12.82%) experienced hemorrhagic events and 27 (34.62%) experienced thrombotic events. Male,patients aged ≥ 60 years, and patients with a JAK2V617F mutation were more likely to experience thrombotic events (P<0.05). Patients with thrombotic events had higher platelet (PLT) counts and fibrinogen (FIB) levels than patients without hemorrhagic-thrombotic events (P<0.05).White blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB) level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and international normalized ratio (INR) showed no statistical difference between patients with thrombotic events and patients without hemorrhagic-thrombotic events (P>0.05). There was also no significant difference in the above-mentioned indexes between patients with hemorrhagic events and patients without hemorrhagic-thrombotic events (P>0.05). Among JAK2V617F positive myeloproliferative neoplasm patients, male patients were more likely to have thrombotic events (P<0.05), and patients with thrombotic events had higher platelet counts than those without hemorrhagic-thrombotic events (P<0.05). There was no significant difference in age, white blood cell count, red blood cell count, hemoglobin level, PT, APTT, FIB, TT or INR between patients with thrombotic events and patients without hemorrhagic-thrombotic events (P>0.05).@*CONCLUSION@#Sex, age, JAK2V617F mutation and platelet count have a certain value for predicting thrombosis in patients with myeloproliferative neoplasms.

Prognostic factors and treatment of neuroendocrine tumors of the uterine cervix based on the FIGO 2018 staging system: a single-institution study of 172 patients.

OBJECTIVE: This study aimed to explore the prognostic factors and outcomes of patients with neuroendocrine tumors (NETs) of the cervix and to determine appropriate treatment. METHODS: A single-institution retrospective analysis of 172 patients with NETs was performed based on the new International Federation of Gynecology and Obstetrics (FIGO 2018) staging system. RESULTS: Among the 172 eligible patients, 161 were diagnosed with small cell neuroendocrine carcinoma (SCNEC), six with large cell neuroendocrine carcinoma, four with typical carcinoid tumors and one with SCNEC combined with an atypical carcinoid tumor. According to the FIGO 2018 staging guidelines, 31 were stage I, 66 were stage II, 57 were stage III, and 18 were stage IV. The 5-year survival rates of patients with stage I-IV disease were 74.8%, 56.2%, 41.4% and 0%, respectively. The 5-year progression-free survival rates of patients with stage I-IV disease were 63.8%, 54.5%, 30.8% and 0%, respectively. In the multivariate analysis, advanced FIGO stage, large tumor and older age were identified as independent variables for 5-year survival in patients with stage I-IV disease. FIGO stage, tumor size and para-aortic lymph node metastasis were independent prognostic factors for 5-year progression-free survival in patients with stage I-IV disease. For the patients receiving surgery (n = 108), tumor size and pelvic lymph node metastasis were independent prognostic factors for 5-year survival, and pelvic lymph node metastasis for 5-year progression-free survival. In stage IVB, at least six cycles of chemotherapy (n = 7) was associated with significantly better 2-year OS (83.3% vs. 9.1%, p < 0.001) and 2-year PFS (57.1% vs. 0%, p = 0.01) than fewer than six cycles of chemotherapy(n = 11). CONCLUSION: Advanced FIGO stage, large tumor, older age and lymph node metastasis are independent prognostic factors for NETs of the cervix. The TP/TC and EP regimens were the most commonly used regimens, with similar efficacies and toxicities. Standardized and complete multimodality treatment may improve the survival of patients with NETs.

Expression and significance of microparticles from peripheral blood of patients with ankylosing spondylitis / 中华风湿病学杂志

Objective:To study the expression and significance of microparticles (MPs), platelets microparticles (PMPs), CD41a +CD62P +PMPs from peripheral blood of patients with ankylosing spondylitis. Methods:Plasma were collected from 47 ankylosing spondylitis (AS) patients and 15 healthy volunteers. The levels of MPs, PMPs, and CD41a +CD62P +PMPs in plasma of AS patients and healthy controls (HC) were detected by flow cytometry. The clinical parameters including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath ankylosing spondylitis disease activity index (BASDAI) were obtained. T test and Spearman linear correlation analysis were used for statistical analysis. Results:The levels of MPs, PMPs, CD41a + CD62P + PMPs in plasma from AS patients were higher than those in plasma from HC [(3 466±641)/μl vs (619±152)/μl, t=2.342, P=0.022; (3 059±628)/μl vs (320±143)/μl, t=2.298, P=0.025; (566±121)/μl vs (47±22)个/μl, t=2.295, P=0.025]. The levels of MPs in plasma of AS patients were positively correlated with BASDAI ( r=0.555, P=0.000 4); and the levels of PMPs in AS patients were positively correlated with BASDAI ( r=0.542, P=0.000 6) but the CD41a +CD62P +PMPs in AS patients were not correlated with BASDAI ( r=0.298, P=0.073 2). The levels of MPs in plasma from AS patients were not correlated with ESR, CRP ( r=-0.016, P=0.917; r=0.035, P=0.817); PMPs in plasma from AS patients were not correlated with ESR, CRP ( r=-0.001, P=0.996; r=0.065, P=0.671). CD41a +CD62P +PMPs in plasma of AS patients were not correlated with ESR, CRP ( r=-0.129, P=0.400; r=-0.410, P=0.789). Conclusion:There is increased expression of MPs, PMPs and CD41a +CD62P +PMPs in AS patients, which is related with disease activity. MPs, PMPs may be involved in the inflammatory response of AS.

Construction of quality evaluation index system for palliative care in ICU / 中国实用护理杂志

Objective:To construct a palliative care quality evaluation index system in ICU, and to provide guidance for implementing high-quality palliative care in ICU.Methods:The questionnaire was designed by literature review, qualitative interview and questionnaire survey, and 20 experts were inquired in two rounds by Delphi method from September to November 2020.Results:After two rounds of letter consultation, experts′ response rates were 80% and 100% respectively, experts′ authority coefficient was 0.873, and coordination coefficient of experts′ opinion were 0.198 and 0.176 respectively. The quality evaluation index system for palliative care in ICU included 6 first-level indicators, 22 second-level indicators and 95 third-level indicators.Conclution:The constructed evaluation system for palliative care is scientific and reliable,which can provide guidance for the implementation and development of ICU high-quality palliative care in China.

Effect of Guizhi Fulingwan on Ovulation Dysfunction in PCOS-IR Rats by Regulating PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

Objective:To investigate the effect of Guizhi Fulingwan on ovulation dysfunction in rats with polycystic ovary syndrome with insulin resistance （PCOS-IR） induced by letrazole combined with high fat emulsion. Method:A total of 72 female SD rats were randomly divided into control group， model group， metformin group and Guizhi Fulingwan low， medium and high dose groups， with 12 rats in each group. Except for control group， rats were given letrozole 0.001g·kg^-1 combined with high-fat emulsion 15 mL·kg^-1 for 21 consecutive days to establish model of PCOS-IR. Guizhi Fulingwan low， medium and high-dose groups were administrated with Guizhi Fulingwan 0.31， 0.62， 1.24 g·kg^-1 respectively， metformin group was administrated with metformin 0.27 g·kg^-1， control group and model group were administrated with 12 mL·kg^-1 of normal saline daily for 30 days. Hematoxylin-eosin（HE） staining was used to observe ovarian tissue pathology morphology， and enzyme-linked immunoassay method （ELISA） was used to detect serum follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， fasting insulin （FINS） level，and LH/FSH and insulin resistance index （HOMA-IR） were calculated． Western blot was used to detect the expression levels of autophagy key molecular Atg6 yeast homologue （Beclin-1）， autophagy related gene 5（Atg5）， microtubule associated protein light chain 3 （LC3） Ⅱ proteins in the phosphatidylinositol 3-kinase/protein kinase B/rapamycin target protein （PI3K/Akt/mTOR） signaling pathway and autophagy related indicators in rat ovarian tissue. Beclin-1 and LC3Ⅱ protein expressions were detected by immunohistochemistry （IHC）. Result:Compared with control group， the thickness of follicles and follicular granulosa cells in the ovary of the model group also decreased， and the number of corpus luteum significantly decreased， while the white membrane thickness of the ovary increased， and the number of atresia follicles and cystic dilatation follicles increased significantly. Serum T， LH， LH/FSH， FINS， FINS， HOMA-IR were significantly increased （<italic>P</italic><0.01）. Phosphorylated （p） -PI3K， p-Akt， and p-mTOR proteins in ovarian tissue were all decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）. The relative expression levels of autophagy-related protein LC3Ⅱ and Beclin-1 were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with model group， the number of follicles in the low， medium and high dose Guizhi Fulingwan group and the metformin group decreased， the number of follicles in atresia and atresia increased， and the follicular granulosa cell layer thickness increased. Serum T， LH， LH/FSH， FINS and HOMA-IR of Guizhi Fulingwan group were significantly decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）， and serum FINS and HOMA-IR of metformin group were significantly decreased （<italic>P</italic><0.01）. The expressions of p-PI3K， p-Akt， and p-mTOR proteins were increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. The expression levels of LC3Ⅱ， Atg5 and Beclin-1 in the medium and high dose groups were significantly decreased （<italic>P</italic><0.01）. Conclusion:Guizhi Fulingwan can activate the PI3K/Akt/mTOR signaling pathway of granular cells， inhibit excessive autophagy of granular cells， improve ovarian function and insulin resistance， and restore ovulation， and the effect is better with high dose.

Effect of Guizhi Fulingwan on Autophagy of Ovarian Granulosa Cells in Mice with Polycystic Ovary Syndrome / 中国实验方剂学杂志

Objective:To investigate the effect of Guizhi Fulingwan on autophagy of ovarian granulosa cells in mice with polycystic ovary syndrome （PCOS）. Method:Twenty SD mice were randomized into a normal group （<italic>n</italic>=10） and a PCOS model group （<italic>n</italic>=10）， followed by PCOS modeling and <italic>in vitro</italic> culture of extracted ovarian granulosa cells. The ovarian granulosa cells of normal mice were classified into the control group and treated with 10% blank serum while those of PCOS mice into the experimental groups and with 10% Guizhi Fulingwan-containing serum at different concentrations （17.6， 35.1， 70.2 mg·kg^-1） and 10% metformin-containing serum （25 mg·kg^-1）， respectively， for 72 h. During the modeling， the changes in mouse body weight were measured. After modeling， the ovarian morphology was observed by microscopy， and the fasting blood glucose （FBG） was measured by Roche glucometer. Following the detection of fasting insulin （FI） and testosterone （T） levels by radioimmunoassay， the proliferation of ovarian granulosa cells was determined using cell counting kit-8 （CCK-8） to figure out the maximal dose of drug-containing serum that did not obviously affect the cell viability for subsequent assay. The autophagy of ovarian granulosa cells was examined by flow cytometry， and the protein expression levels of intracellular microtubule-associated protein 1 light chain 3Ⅰ （LC3Ⅰ）， LC3Ⅱ， Beclin1， and p62 were assayed by Western blott. Result:Compared with the blank group， the model group showed increased body weight and elevated FI， FBG， and T levels （<italic>P</italic><0.05，<italic>P</italic><0.01）， indicating the successful modeling of PCOS mice. Flow cytometric assay proved that the incubation with 10% Guizhi Fulingwan serum-containing medium resulted in a decline of autophagy （<italic>P</italic><0.05）. As demonstrated by Western blot assay results， the protein expression levels of Beclin1 and LC3 Ⅱ/Ⅰ in the model group increased significantly as compared with those of the blank group， whereas the expression level of p62 decreased significantly （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， the medium- and high-dose Guizhi Fulingwan groups exhibited significantly down-regulated Beclin1 and LC3 Ⅱ/Ⅰ levels but remarkably up-regulated p62 （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Guizhi Fulingwan inhibits the autophagy of ovarian granulosa cells by down-regulating the protein expression levels of Beclin1 and LC3 Ⅱ/Ⅰ.