High-fat intake alleviates lung injury induced by Paragonimus proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues / 中国血吸虫病防治杂志

Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

Investigation and analysis of influencing factors of the needs for smart elderly care services among community older adults in main urban areas of Chongqing / 中国实用护理杂志

Objective:To investigate status quo of smart elderly care needs of community older adults in main urban areas of Chongqing, and to analyze the influencing factors.Methods:A survey, using convenience sampling method, involving 452 community older adults in 9 districts in urban areas of Chongqing, was conducted by the General questionnaire and Smart Elderly Care Needs questionnaire from October to December, 2021. And analyze the influencing factors of the demand for smart elderly care needs.Results:In the demand for smart elderly care needs of the community elderly in the main urban area of Chongqing, the scores of needs for daily life care, social and emotional support, daily medical care and emergency medical assistance were 3.39 ± 1.45, 3.60 ± 1.28, 3.80 ± 1.19 and 3.87 ± 1.27, respectively. The results of ordinal Logistic analysis showed that gender, age, living alone and education level were the influencing factors of daily life care needs( P<0.05). Age and living alone were the influencing factors of social and emotional support and emergency medical assistance needs( P<0.05). Daily medical care needs were influenced by living alone( P<0.05). Conclusions:Community older adults in main urban areas of Chongqing have high level of needs for smart elderly care. Smart elderly care should focus on the ones with higher demand, namely those living alone, older, male and poorly educated, so as to promote active aging.

Adult hemophagocytic syndrome in emergency department setting: the implications of hormone therapy on diagnosis and prognosis / 中华急诊医学杂志

Objective:To assess the implications of hormone therapy on confirmation of clinical diagnosis and prognosis of adult hemophagocytic syndrome (HPS) in the emergency department setting.Methods:The eligible 34 patients admitted with suspected HPS in the Emergency Department of Peking University People's Hospital from September 2019 to August 2021 were respectively collected. The patients were divided into the death group and survival group according to the prognosis and divided into early hormone therapy group and standard hormone therapy group according to the timing of hormone application. Patients in the early hormone therapy group were divided into the routine 4 criteria group and non-routine 4 criteria group according to the conditions of meeting the four HLH-2004 diagnostic criteria. Medical records of the following were collected and statistically analyzed: complete blood count, blood biochemical index, coagulation function, serum ferritin, NK cell activity, sCD25 level, peripheral blood smear, bone marrow biopsy, abdominal ultrasound scan, and abdominal CT on admission, and recheck the clinical indicators such as blood count, blood biochemical index and blood coagulation dunction 5-7 days later.Results:①Patients from the death group were older, with higher APACHEⅡ scores and SOFA scores, higher total bilirubin, and lower serum albumin. ② Univariate Logistic analysis showed age ( OR=1.098, CI: 1.019-1.183, P=0.014), APACHE Ⅱ score ( OR=1.144, CI: 1.017-1.285, P=0.024), SOFA score ( OR=1.441, CI: 1.079-1.925, P=0.013) were associated with the risk of death. Multivariate Logistic analysis showed that age ( OR=1.099, CI: 1.014-1.190, P=0.021) was associated with the risk of death. There was no significant correlation between early hormone therapy and clinical prognosis. Kaplan-Meier survival curves showed that there was no difference in the 60-day survival rate between the early hormone therapy group and the standard hormone therapy group. ③ The level of triglyceride still increased after early hormone therapy, and the number of indexes meeting the diagnostic criteria of HLH-2004 increased significantly. All patients met the criteria of Hscore>169, and 3 patients did not meet at least 5 diagnostic criteria of HLH-2004, accounting for 16.7% of the total cases of early hormone therapy. ④ Starting hormone therapy when the four HLH-2004 diagnostic criteria were met could reduce the length of hospital stay. Prothrombin time and activited partial thomboplastin time were closer to normal levels in patients 5-7 days after treatment. Early hormone therapy had no significant effect on treatment response and in-hospital death risk. There were no significant differences in APACHE Ⅱ score, SOFA score, confirmation of diagnosis, treatment response, clinical prognosis, and related clinical indicators after hormone therapy between the routine 4 criteria and non-routine 4 criteria groups. Conclusions:Initiation of early hormone therapy has no significant effect on the confirmation of clinical diagnosis, treatment response, in-hospital mortality, and 60-day survival rate of patients with HPS, and can quickly correct coagulation dysfunction and effectively reduce the length of hospital stay. An earlier start of hormonal therapy (meeting the four HLH-2004 diagnostic criteria) may be considered by the emergency physician when a patient is highly suspected of HPS diagnosis

Comparison of cognitive function in children with different subtypes of attention deficit hyperactivity disorder / 中华行为医学与脑科学杂志

Objective:To explore the heterogeneity of behavioral problems and cognitive function of three subtypes of attention deficit hyperactivity disorder(ADHD), and to analyze the related factors of cognitive function.Methods:The outpatients with ADHD were evaluated by Wechsler children′s intelligence test (C-WISC), SNAP-Ⅳ parental rating scale (SNAP-Ⅳ), Conners parental symptom questionnaire (PSQ) and 12 online cognitive function tests. The differences of behavioral problems and cognitive function of children with different subtypes of ADHD, and the correlation between their intelligence level, PSQ, SNAP-Ⅳ and cognitive function were compared by SPSS 22.0 software.Results:The results of PSQ questionnaire showed that ADHD-C ((1.11±0.59), (1.59±0.58), (1.62±0.50)) had higher behavior problems, impulse-hyperactivity and hyperactivity index than ADHD-I ((0.64±0.27), (1.01±0.54), (1.09±0.32)) and ADHD-HI ((0.75±0.35), (1.22±0.58), (1.05±0.38)) ( F=9.374, F=7.644, F=15.176, P<0.05), while ADHD-C (2.01±0.55) had higher learning problems than ADHD-I (1.66±0.58) and ADHD-HI (1.16±0.43) ( F=11.709, P<0.05). In terms of cognitive function, there were differences in language understanding ability, digital reasoning ability, sequence relationship and short-term memory ability ( χ2=6.734, 7.192, 7.822, 8.646, all P<0.05) among the three groups of ADHD children. ADHD-HI (4.00(4.00, 5.00), 5.00(4.25, 6.00), 5.00(4.00, 7.00)) had better language understanding ability, digital reasoning ability and sequence relationship than ADHD-I (3.00(2.00, 5.00), 3.00(2.50, 6.00), 4.00(3.00, 5.50)). The short-term memory ability of ADHD-HI (5.00(4.00, 6.00)) and ADHD-C (5.00(4.00, 6.00)) were better than that of ADHD-I (4.00(3.00, 5.00)). The intellectual structure of ADHD children was positively correlated with spatial cognitive ability, sequential relationship, Raven reasoning test, short term memory span and Wisconsin card sorting test ( r=0.25-0.57, all P<0.05). Children′s learning problems and psychosomatic problems were negatively correlated with their digital comprehension ability ( r=-0.26, -0.25, both P<0.05). Conclusion:The behavioral problems and cognitive function of children with different subtypes of ADHD are different and have a certain correlation.

Adhere to the people-centered approach and actively respond to the aging of the population—there is a lot to be done for nursing / 中国实用护理杂志

Effective response to the aging of China′s population bears on the overall development of the country and the well-being of hundreds of millions of people. From the elderly social participation, intelligent media use and calm better death as the entry point actively promote healthy aging, happy aging through the community nursing, information nursing, hospice care and other perspectives. Nursing has always adhered to the people-centered, social reality needs as the guidance. It is expected to provide reference for improving the welfare construction of the broad masses of people represented by the elderly and facilitating the all-round promotion of the Healthy China strategy.

Comparison of Endocrine Therapies in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer:A Network Meta-Analysis / 한국유방암학회지

We aimed to explore what kind of endocrine treatments are optimal for hormone receptorpositive and human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer in some specific clinical situations. We searched randomized controlled trials in Embase, Medline, the Cochrane library, and PubMed from inception to April 1, 2020 and performed a network meta-analysis based on a Bayesian fixed-effects model. Progression-free survival (PFS) with hazard ratios and corresponding 95% confidence interval was defined as the primary endpoint, while overall survival (OS), objective response rate (ORR), clinical benefit rate and serious adverse events were used as secondary endpoints. A total of 35 studies involving 12,285 patients and 24 treatment options were included. In general, most co-treatment options prolonged PFS compared to single-agent therapy, of which aromatase inhibitor (AI) plus everolimus and fulvestrant plus palbociclib were probably the most effective agents, and the latter had the best safety record. However, despite the superior efficacy of fulvestrant plus capecitabine for PFS and OS, palpable toxic effects have been demonstrated for this treatment, so its application must be scrupulously considered. The results of subgroup analysis indicated that fulvestrant combined with palbociclib improved prognosis for phosphatidylinositol 3-kinase (PI3K)-mutated patients, PI3K-unmutated patients, patients with endocrine therapy resistance, and visceral metastatic patients, while no obvious improvement was detected in OS. Moreover, the efficacy of fulvestrant plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was slightly better than that of AI plus CDK4/6 inhibitors, while AI plus everolimus was more efficacious than fulvestrant combined with everolimus in terms of PFS, OS, and ORR. In conclusion, our results provide moderate evidence that fulvestrant plus palbociclib and AI plus everolimus were the most effective treatments, while the efficacy and safety of fulvestrant plus palbociclib was obviously superior in some specific clinical situations.

Diagnosis and treatment of posttransplant lymphoproliferative diseases in liver transplant recipients: a single-center experience / 器官移植

Objective To summarize the incidence, diagnosis and treatment experience of posttransplant lymphoproliferative diseases (PTLD) in the liver transplant recipients. Methods Clinical data of 734 liver transplant recipients were retrospectively analyzed. The incidence, clinical symptoms, laboratory and imaging data of PTLD in liver transplant recipients were collected. The pathological results and treatment methods of PTLD recipients were analyzed. The prognosis of PTLD recipients was evaluated. Results The incidence of PTLD in liver transplant recipients was 2.2% (16/734). The median time of onset after operation was 8(3, 46) months. The main clinical manifestations of PTLD were fever and lymph nodes enlargement. Some patients developed anemia, hepatosplenomegaly, abnormal liver function and digestive system symptoms, etc. Among 16 PTLD recipients, 1 case showed abnormal increase in blood concentration of tacrolimus, 6 cases of elevated transaminase levels, 14 cases of increased Epstein-Barr virus (EBV) DNA load and 5 cases of increased cytomegalovirus (CMV) DNA load. Positron emission tomography and computed tomography (PET/CT) showed hypermetabolism of 18F-flurodeoxyglucose in the enlarged lymph nodes of 13 recipients. CT scan of the neck and abdomen indicated multiple lymph node enlargement in the corresponding area of 2 recipients. Lymph nodes enlargement of 1 recipient showed on ultrasound only. All 16 PTLD recipients received pathological examination. In situ hybridization showed that EBV-encoded small RNA (EBER) was positive in 13 recipients. Reducing the immunosuppressant level was the basal treatment plan for PTLD recipients, and it can be combined with rituximab-targeted therapy and chemotherapy according to different pathological types of PTLD. Surgery and radiotherapy were used for enlarged lymph nodes. One recipient died of transplant liver failure due to PTLD treatment. Conclusions Administration of immunosuppressants after liver transplantation can increase the risk of PTLD. The incidence of PTLD is higher in pediatric liver transplant recipients than in adults. Early diagnosis and reasonable treatment can significantly improve the prognosis of PTLD recipients.

Phenotypic and genotypic analysis of a pedigree affected with hereditary protein C deficiency due to heterozygous deletional mutation of PROC gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the phenotype and genetic variants of a pedigree affected with hereditary protein C (PC) deficiency.@*METHODS@#The protein C activity (PC:A) of the proband and her family members (a four-generation pedigree including 11 individuals) were tested by chromogenic substrate method, and the protein C antigen (PC:Ag) was detected with an enzyme-linked immunosorbent assay(ELISA). The 9 exons and flanking sequences of the protein C (PROC) gene were amplified by PCR and directly sequenced. Suspected mutation was validated by clone sequencing and in other members of the family. MutationTaster and ClustalX-2.1-win was used to analyze the pathogenicity and conservation of the mutation site,respectively. Three-dimentional protein model and amino acids interaction were analyzed with Swiss-PdbViewer software.@*RESULTS@#The PC: A and PC: Ag of the proband were decreased to 46% (reference range: 70%-130%) and 50% (referencerange:70%-140%), respectively. Her grandmother,aunt, cousin and younger brother also showed declined PC:A and PC:Ag by approximately 50%. Genetic analysis revealed that the above individuals have all carried a deletional mutation c.1212-1212delG (p.Met364TrpfsX15) in exon 9 of the PROC gene which can cause replacement of Methionine at position 364 by Tryptophan and alteration of 15 downstream amino acids, and produce a premature stop codon at position 378. The score of MutationTaster was 1.000, indicating that the variant is pathogenic. Conservative analysis showed that the 15 altered amino acids are located in a conserved region across nine homologous species. Protein model analysis showed that the mutation has disrupted a catalytic domain of protein C thereby affected its function.@*CONCLUSION@#The heterozygous c.1212-1212delG deletional mutation in exon 9 of the PROC gene, which was unreported previously,probably accounts for the decrease of PC:A and PC:Ag in this pedigree.

Clinical characteristics and genetic analysis of a combined inherited antithrombin and factor Ⅶ deficiency pedigree / 中华检验医学杂志

Objective:To study the clinical characteristics and gene mutations in a family with combined inherited antithrombin (AT) and factor Ⅶ (FⅦ) deficiency, and explore the relationship between AT gene, F7 gene mutations and diseases. Methods:Pedigree investigation. Blood samplesand clinical dataswere collected fromthe proband and her family members (a total of 16 people in 3 generations) who admitted to the First Affiliated Hospital of Wenzhou Medical University in November 2018. The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), antithrombin activity (AT: A), antithrombin antigen (AT: Ag), protein C activity (PC: A), protein S activity (PS: A), FⅦ activity (FⅦ: C), FⅦ antigen (FⅦ: Ag) and other indicators were detectedto confirm the diagnosis. DNA direct sequencing analysis of all exons, flanking sequences, 5′ and 3′ untranslated regions of AT genes and F7 genes, and the mutation sites were confirmed by clone sequencingor reverse sequencing. Results:The AT: A and AT: Ag of the proband were 46% and 135 mg/L, respectively (reference range: 250-360 mg/L), some of her family members′ s (father, aunt, two cousins, younger brother and nephew) AT: A and AT: Ag were reduced to 50% of normal range. Her father (Ⅰ 2), aunt (Ⅰ 4), elder brother (Ⅱ 7), younger brother (Ⅱ 8), and nephew (Ⅲ 3)′s FⅦ: C were 45%, 50%, 48%, 47% and 48%, respectively; and their FⅦ:Ag was within the normal range. Genetic analysis revealed that the proband(Ⅱ 6) and some of her family members (father, aunt, two cousins, younger brother and nephew) took rs3138521 polymorphism in the 5′ untranslated region of AT gene. Her father (Ⅰ 2), aunt (Ⅰ 4), elder brother (Ⅱ 7), younger brother (Ⅱ 8), nephew (Ⅲ 3) took c.1091G>A heterozygous missense mutationin exon 8 of F7 gene, resulting in p.Arg304Gln. Conclusion:The rs3138521 in AT gene and c.1091G>A in F7 gene, which may be the molecular mechanism leading to combined inherited AT and FⅦ deficiency in this family.

Optimized anaesthetic strategy for laparoscopic pancreaticoduodenectomy: erector spinae plane block combined with general anesthesia / 中华麻醉学杂志

Objective:To evaluate the optimized effect of erector spinae plane block (ESPB) combined with general anesthesia when used for the patients undergoing laparoscopic pancreaticoduodenectomy.Methods:Sixty-eight American Society of Anesthesiologists physical status Ⅱ orⅢ patients of both sexes, aged 18-64 yr, with body mass index of 18-24 kg/m 2, scheduled for elective laparoscopic pancreaticoduodenectomy, were divided into general anesthesia group (group G, n=34) and ESPB combined with general anesthesia group (group EG, n=34) using a random number table method.In group E, ultrasound-guided ESPB was performed before induction with general anesthesia, and 0.375% ropivacaine 20 ml was injected into both sides.Total intravenous anesthesia was applied in both groups.Patient-controlled intravenous analgesia (PCIA) with sufentanil 1.5 g/kg in 100 ml of normal saline was performed after surgery.The PCIA pump was set up to deliver a 2 ml bolus dose with a 5-min lockout interval and background infusion at 3 ml/h.Analgesia was performed until 24 h after operation, and the visual analogue scale score at rest was maintained at ≤4.Sufentanil 0.1 g/kg was intravenously injected as rescue analgesic when visual analogue scale score >4.The extubation time and occurrence of intraoperative cardiovascular events were recorded.The amount of sufentanil used during operation and within 24 h after operation was recorded.The time to first pressing the analgesia pump after operation and effective pressing times of PCA within 24 h after operation were recorded.Time to first flatus, first ambulation time and length of postoperative hospital stay were recorded.The development of postoperative adverse reactions such as nausea and vomiting, irritability and respiratory depression within 24 h after operation was recorded. Results:Compared with group G, the incidence of intraoperative hypertension and tachycardia was significantly decreased, the extubation time was shortened, the consumption of sufentanil during operation and within 24 h after operation was reduced, the time to first pressing the analgesia pump was prolonged, the effective pressing times of PCA within 24 h after operation were reduced, time to first flatus, first ambulation time and length of postoperative hospital stay were shortened, and the incidence of nausea and vomiting, irritability and respiratory depression within 24 h after operation was decreased in group EG ( P<0.05). Conclusion:The combination of ESPB and general anesthesia is helpful in achieving an anesthesia mode of lower opioid consumption and more helpful for inhibition of postoperative pain responses and for early postoperative recovery than general anesthesia alone when used for the patients undergoing laparoscopic pancreaticoduodenectomy.

Analysis of a Chinese pedigree affected with hereditary factor VII deficiency caused by compound heterozygous variants of F7 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular basis for a Chinese pedigree affected with hereditary coagulation factor VII (FVII) deficiency.@*METHODS@#The coding regions of F7 gene were amplified by PCR and sequenced. Suspected variants were confirmed by reverse sequencing and validated in other members from the pedigree. Pathogenicity of the variants was analyzed with multiple bioinformatic tools.@*RESULTS@#Genetic analysis revealed that the proband has carried compound heterozygous c.985T>C (p.Ser329Pro) and c.1091G>A (p.Arg364Gln) variants in exon 8 of the F7 gene. Her mother, brother and son were heterozygous for c.985T>C (p.Ser329Pro), while her father was heterozygous for c.1091G>A (p.Arg364Gln). Phylogenetic analysis suggested that both p.Ser329 and p.Arg364 are highly conserved among homologous species. Online bioinformatic software predicted both variants to be deleterious. Protein model analysis suggested that the Pro329 side chain may form a new hydrogen bond with Leu333. The Pro benzene ring may clash with Glu325 in the p.Ser329Pro variant model. The p.Arg364Gln variant have two additional hydrogen bonds compared with wild type Arg364. Both variants may lead to alteration of the protein structure.@*CONCLUSION@#The p.Ser329Pro and p.Arg364Gln variants in exon 8 of the F7 gene probably account for the reduced FVII in this pedigree.

Comparison of Endocrine Therapies in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer:A Network Meta-Analysis / 한국유방암학회지

We aimed to explore what kind of endocrine treatments are optimal for hormone receptorpositive and human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer in some specific clinical situations. We searched randomized controlled trials in Embase, Medline, the Cochrane library, and PubMed from inception to April 1, 2020 and performed a network meta-analysis based on a Bayesian fixed-effects model. Progression-free survival (PFS) with hazard ratios and corresponding 95% confidence interval was defined as the primary endpoint, while overall survival (OS), objective response rate (ORR), clinical benefit rate and serious adverse events were used as secondary endpoints. A total of 35 studies involving 12,285 patients and 24 treatment options were included. In general, most co-treatment options prolonged PFS compared to single-agent therapy, of which aromatase inhibitor (AI) plus everolimus and fulvestrant plus palbociclib were probably the most effective agents, and the latter had the best safety record. However, despite the superior efficacy of fulvestrant plus capecitabine for PFS and OS, palpable toxic effects have been demonstrated for this treatment, so its application must be scrupulously considered. The results of subgroup analysis indicated that fulvestrant combined with palbociclib improved prognosis for phosphatidylinositol 3-kinase (PI3K)-mutated patients, PI3K-unmutated patients, patients with endocrine therapy resistance, and visceral metastatic patients, while no obvious improvement was detected in OS. Moreover, the efficacy of fulvestrant plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was slightly better than that of AI plus CDK4/6 inhibitors, while AI plus everolimus was more efficacious than fulvestrant combined with everolimus in terms of PFS, OS, and ORR. In conclusion, our results provide moderate evidence that fulvestrant plus palbociclib and AI plus everolimus were the most effective treatments, while the efficacy and safety of fulvestrant plus palbociclib was obviously superior in some specific clinical situations.

Effects of RhoGDI2 gene silencing by siRNA on proliferation and invasion of colon carcinoma cell lines / 中国免疫学杂志

Objective:To study the silencing gene expression level of RhoGDI2 small interfering RNA(siRNA)and the colorectal cancer cell malignant behaviors such as cell proliferation,migration,invasion.Methods:Testing RhoGDI2 expression using Westen blot analysis and Real-time reverse transcription polymerase chain reaction(RT-qPCR)in the colorectal cancer cell lines of RKO,HT29,SW620,SW480,HCT116.The siRNA of RhoGDI2 with Lipofecta mineTM2000 was transfected into target cells,as well as negative control and normal control groups.Cell counting kits(CCK-8)to detect proliferation,Wound healing assay and the Transwell plate migration and invasion was detected.The epithelial-mesenchymal transition(EMT)relevant protein E-cadherin/Vimentin expression was detected.Results:Human colon cancer cell lines RhoGDI2 expression levels decreased in the order of RKO,HT29,SW620,SW480,HCT116:siRNA inhibited RhoGDI2 expression rate of RKO cell by 70%;in silence group,negative control group and blank contro1 group,the proliferation rates were(0.683±0.013),(0.866±0.088),(0.905±0.008),P<0.05;Wound healing assay and Transwell assay suggested RhoGDI2 silencing could inhibit migration;siRNA interference of colon cancer cells downregulated Vimentin,but upregulated E-Cadherin protein.Conclusion:RhoGDI2 down-regulation could significantly inhibit the cell proliferation,migration,invasion of colon cancer cell.

RhoGDI2 expression and clinical significance in colorectal cancer / 中国免疫学杂志

Objective:To explore the expression and clinical significance of RhoGDI2 in colorectal cancer. Methods:Immuno-histochemistry was used to identify RhoGDI2 expression in clinical samples of colorectal cancer tissues,para-tumorous tissues and lymph node metastasis tissues. The relationships between CRC clinical factors and survival were analyzed. Results: RhoGDI2 expression contributed positively with tumor progression and metastasis in clinical tissues. It was associated with the stage of the tumor,lymph node metastasis, remote metastasis, venous invasion and vessel invasion. Patients with higher RhoGDI2 expression had poorer overall survival. Conclusion:RhoGDI2 showed high expression in colorectal cancer and it was associated with the stage of the tumor,lymph node metastasis,remote metastasis, venous invasion and vessel invasion. Patients with higher RhoGDI2 expression had poorer overall survival.

Effects of IL-12 combined with GM-CSF on apoptosis of H22 hepatoma cells / 中国综合临床

Objective To investigate the effects of granulocyte macrophage colony-stimulating factor (GM-CSF) combined with interleukin-12 (IL-12) genes on apoptosis of hepatoma cells.Methods The hepatoma cell lines were cultured in vitro and were divided into four groups: GM-CSF transfection group,IL-12 transfection group,GM-CSF and IL-12 co-transfection group,negative control group (empty load group),respectively.The PIB-CMV3-GM-CSF and PIB-CMV3-IL-12 eukayotic expression vector was built,and 36 h after transfection,fluorescence microscope was used to detect the transfection effect;the expression level of IL-12,GM-CSF,p53,p38 and C-JUN mRNA were detected by RT-PCR,and Western blot was used to examine the expression level of IL-12,GM-CSF,p53,p38 and C-JUN protein.In addition,the flow cytometry was applied to detect cell apoptosis.Results Through fluorescence microscope,green fluorescence was observed in cells of GM-CSF transfection group,IL-12 transfection group,GM-CSF and IL-12 co-transfection group,indicating that the plasmid has successfully transferred into cells.In addition,the expression of p53mRNA in empty load group,GM-CSF transfection group,IL-12 transfection group,GM-CSF and IL-12 co-transfection group were 1.2±0.10,4.3±0.98,4.2±0.34,9.2±0.87,and the protein expression were 1.0±0.10,3.6±0.34,3.8±0.30,5.0±0.60.Compared with the empty load group,the expression level of p53 mRNA and protein were significantly increased in the three plasmid transfection groups (P<0.01).The expression of p53 mRNA and protein were significantly increased in co-transfection group than GM-CSF group and IL-12 group (P<0.01),while in the comparison with GM-CSF transfection group and IL-12 transfection group,the expression level of p53mRNA and protein in the co-transfection group could be improved to a higher degree(P<0.01).Meanwhile,p38 C-JUN mRNA expression levels in empty load group,GM-CSF transfection group,IL-12 transfection group,GM-CSF and IL-12 co-transfection group were as follows: 7.5± 0.9,3.5±0.45,3.7±0.25,1.0±0.11,while p38protein expression levels were 10.1±1.03,6.1± 0.67,7.1 ± 0.61,1.0 ± 0.12,respectively,C-JUN mRNA expression levels were 11.2 ± 1.20,4.1 ± 0.19,3.3 ± 0.30,1.0 ± 0.01,separately,C-JUN protein expression levels were 2.25 ± 0.2,1.8 ± 0.13,1.4 ± 0.12,1.0 ± 0.09.P38, C-JUN mRNA and protein levels were significantly reduced in the three plasmid transfection groups compared with the empty load group (P<0.01).The expression of p38,C-JUN mRNA and protein were reduced to a lower degree in co-transfection group than in GM-CSF transfection group and IL-12 transfection group (P<0.01).Flow cytometer showed that the hepatoma cell apoptosis rate of the empty load group,GM-CSF transfection group,IL-12 transfection group,co-transfection group were (3.43±0.9)%,(5.87±1.02)%,(7.32±1.1)%,(17.47±2.11)%,the rates of the three plasmid transfection groups were significantly higher than that of the empty load group (P<0.01).And the apoptosis rate was significantly increased in the co-transfected group compared with other plasmid groups (P<0.01). Conclusion The combination of GM-CSF and IL-12 could significantly accelerate the apoptosis of hepatoma cells by up-regulating the expression of p53,and down-regulating the expression of p38 and C-JUN.

Immunoglobulin light chain amyloidosis: new therapy and biomarkers / 中国医师进修杂志

Amyloidosis is a systemic disease whose clinical manifestations and pathological changes are caused by the deposition of amyloid substances in different organs of the body.Kidney is one of the most frequently affected organs of amyloidosis.Amyloid protein should be genotyped in time, with the aim of identifying the precursor protein and identifying the corresponding type of amyloidosis.The use of biomarkers can help identify amyloid precursor, assess the presence and severity of organ involvement, and monitor the response to treatment. In recent years, the serum free light chain (FLCs) can be a biomarker of immunoglobulin light chain amyloidosis, targeting plasma cell antigen CD38(daratumumab) and humanized 2A4 monoclonal antibody NEOD001 is promising for immunoglobulin light chain amyloidosis to be an effective therapeutic agent.

Effect of Dihydromyricetin on High Glucose-induced Glomerular Mesangial Cell Proliferation and Fibro-nectin Accumulation / 中国药房

OBJECTIVE:To study the effect of dihydromyricetin(DMY)on high glucose(HG)-induced glomerular mesangial cell(MCs)proliferation and fibronectin(FN)accumulation,and explore its mechanism for diabetic nephropathy glomerulosclero-sis. METHODS:Cells were divided into normal group(5.5 mmol/L glucose),HG group(30 mmol/L glucose),DMY low-concen-tration,medium-concentration,high-concentration groups (30 mmol/L glucose+22.5,45,90 μmol/L DMY). After incubating 48 h,MTT was used to detect the proliferative activity [reflected by the optical density(OD)value] of cells;molecular docking meth-od was adopted to conduct simulation analysis for DMY binding state with Smad2. Cells were divided into normal group(5.5 mmol/L glucose),HG group (30 mmol/L glucose),DMY group (30 mmol/L glucose+45 μmol/L DMY) and DMY control group (5.5 mmol/L glucose+45 μmol/L DMY). After incubating 5 h,Western blot was used to detect the expression levels of phosphorylated Smad2 (p-Smad2) and extracellular matrix protein FN. RESULTS:Results of MTT detection showed,compared with normal group,OD values in HG group were significantly increased(P<0.05);compared with HG group,OD values in DMY each con-centration group were significantly reduced(P<0.05). The Gibbs free energy(ΔG)of DMY and Smad2 protein was -5.64 kJ/mol, Ki was 73.53 μmol/L,and there were hydrogen bond donor and receptor binding in No. 465,464,461,458 amino acid residues. Results of Western blot showed,compared with normal group,expression levels of p-Smad2 and extracellular matrix protein FN in HG group were significantly increased (P<0.05);compared with HG group,expression levels of p-Smad2 and extracellular ma-trix protein FN in DMY group were significantly decreased(P<0.05). CONCLUSIONS:DMY inhibits HG-induced MCs prolifera-tion and improves diabetic nephropathy glomerulosclerosis by combining with Smad2 and inhibiting Smad2 phosphorylation to re-duce the extracellular matrix protein FN expression.

Clinical-pathological features and prognosis analysis of 218 esophagogastric junction malignant tumor / 中华消化杂志

Objective To explore the relation between clinical-pathological features,Siewert classification and prognosis of esophagogastric junction (EGJ) carcinoma,and to assess the applicability of the new edition of American Joint Committee of Cancer (AJCC) staging guideline on EGJ adenocarcinoma in China.Methods From 2002 to 2012,the clinical data,pathological features,treatment and prognosis of 218 patients with EGJ malignant tumor were retrospectively analyzed.The patients were typed according to Siewert classification criteria and each case was staged according to 7th edition of AJCC TNM staging criteria for esophagus adenocarcinoma and gastric cancer.Kaplan-Meier method and Log-rank test were performed for survival analysis.Results According to the Siewert classification,type Ⅰ was rare (nine cases,4.1％),type Ⅱ was the most common type (150 cases,68.8％) and followed by type Ⅲ (59 cases,27.1％).There was no significant difference in survival curve among the three types (P＞0.05).The survival curve was drawn according to 7th edition of AJCC TNM staging criteria for esophagus adenocarcinoma.In T staging,the prognosis of patients at T4b was better than that of patients at T4a,the prognosis of patients at ⅡB was better than that of patients at ⅡA.The survival curve of patients at Ⅲ C obviously crossed with that of patients at Ⅳ,which was not in conformity with clinical results.The survival curve was drawn according to 7th edition of AJCC staging criteria for gastric cancer.In T staging,the survival curve of patients at Tis was overlapped with that of patients at T1a.The survival rate of patients at ⅡB could not be accurately predicted by the overall staging.In general,the survival of patients with EGJ carcinoma was better predicted according to 7th edition of AJCC staging criteria for gastric cancer than 7th edition for esophagus adenocarcinoma.Conclusions Neither 7th edition of AJCC staging criteria for esophagus adenocarcinoma nor for gastric cancer could accurately predict its prognosis.In our country,EGJ malignant tumor was similar to gastric cancer and had specific clinical-pathological features.It is necessary to research and establish EGJ carcinoma staging criteria instead of applying the current staging criteria for esophagus adenocarcinoma or gastric cancer.

Analysis of histopathological features in 850 cases of esophageal malignant tumor / 中华消化杂志

Objective To explore the histopathological features of 850 patients with esophageal malignant tumor in 10 years.Methods From January 2002 to January 2012, 850 patients diagnosed with esophageal malignant tumor were enrolled.Tumor location, general type, pathological type and TNM stage were retrospectively analyzed.All the data were described as case number and percentage.Results Among the 850 cases of esophageal malignant tumor, 33 lesions (3.9％) located in the neck segment of esophagus, 119 lesions (14.0％) located in the upper segment, 44 lesions (5.2 ％) located in the upper-middle segment, 409 lesions (48.1％) located in the middle segment, 123 lesions (14.5 ％) located in the middle-lower segment, 122 lesions (14.4％) located in the lower segment.Among the 724 eases clearly diagnosed as esophageal malignant tumor by general type, the most cases were ulcer type (305 cases, 42.1％), followed by medulla type (260 cases, 35.9％), fungating type (80 cases, 11.0％) and constrictive type (70 cases, 9.7％), and the least cases were intraluminal type (nine cases, 1.2％).Among the 850 cases of esophageal malignant tumor, squamous cell carcinoma (794 cases, 93.4 ％) was the most common cytological type, followed by small cell carcinoma (19 eases, 2.2％), and the least common cytological type was adenocarcinoma (seven cases, 0.8 ％).Among the 724 cases with clear TNM staging, case number of Tis, T1, T2, T3 and T4 stage was eight (1.1％), six (0.8％), 271 (37.4％), 278 (38.4％) and 161 (22.2％), respectively.Among the 122 cases of distal esophageal carcinomas (104 cases with clear TNM staging), most cases were squamous cell carcinoma (112 cases, 91.8 ％), the others cases were adenocarcinoma (three cases, 2.5 ％), small cell carcinoma (three cases, 2.5 ％), basaloid squamous cell, adenosquamous, neuroendocrine carcinomas and carcinosarcoma (one case in each type, 0.8％).Conclusions Esophageal carcinoma was mostly located in the middle segment of in which squamous cell carcinoma was predominant while adenocarcinoma was less common.Esophageal cancer located at lower segment of esophagus is with a wide range of pathological spectrum, squamous cell carcinoma was still dominant, however, esophageal adenocarcinoma is rare.