The impact of acute-phase reaction on mortality and re-fracture after zoledronic acid in hospitalized elderly osteoporotic fracture patients.

This study involving 674 elderly osteoporotic fracture (OPF) patients undergoing orthopedic surgery investigated the long-term outcomes of acute phase reaction (APR) after initial zoledronic acid (ZOL). Those who had an APR had a 97% higher risk of mortality and a 73% lower rate of re-fracture than patients who did not. INTRODUCTION: Annual infusion of ZOL efficiently decreases the risk of fracture. A temporary APR, consisting of flu-like symptoms, myalgia, and fever, is frequently observed within 3 days after the first dose. This work aimed to identify whether the occurrence of APR after initial ZOL infusion is a reliable indicator of drug efficacy for mortality and re-fracture in elderly OPF patients undergoing orthopedic surgery. METHODS: This retrospectively observed work was constructed on a database prospectively collected from the Osteoporotic Fracture Registry System of a tertiary level A hospital in China. Six hundred seventy-four patients 50 years old or older with newly identified hip/morphological vertebral OPF who received ZOL for the first time after orthopedic surgery were included in the final analysis. APR was identified as a maximum axillary body temperature greater than 37.3 °C for the first 3 days after ZOL infusion. We utilized models of multivariate Cox proportional hazards to compare the risk of all-cause mortality in OPF patients with APR (APR+) and without APR (APR-). Competing risks regression analysis was used to examine the association between the occurrence of APR and re-fracture when mortality was taken into account. RESULTS: In a fully adjusted Cox proportional hazards model, APR+ patients had a significantly higher risk of death than APR- patients with a hazard ratio [HR] 1.97 (95% CI, 1.09-3.56; P-value = 0.02). Furthermore, in an adjusted competing risk regression analysis, APR+ patients had a significantly reduced risk of re-fracture compared with APR- patients with a sub-distribution HR, 0.27 (95% CI, 0.11-0.70; P-value = 0.007). CONCLUSIONS: Our findings suggested a potential association between the occurrence of APR and increased mortality risk. An initial dose of ZOL following orthopedic surgery was found to be protective against re-fracture in older patients with OPFs.

[A pre-conception cohort study of fertility and its related factors among couples with the intention of conception].

Objective: To describe fertility and explore factors associated with it among pre-conception couples of childbearing age. Methods: Based on the pre-conceptional offspring trajectory study of the School of Public Health of Fudan University, couples of childbearing age who participated in the pre-conception physical examination in Shanghai Jiading District from 2016 to 2021 were recruited and followed up. Couples' time to pregnancy (TTP) was analyzed and Cox proportional hazards regression model was used to explore the factors associated with TTP. Kaplan-Meier was used to calculate each menstrual cycle's cumulative pregnancy rate. Results: A total of 1 095 preconception couples were included in the analysis, the M(Q1,Q3)of TTP was 4.33 (2.41, 9.78) menstrual cycles. Age of women (FR=0.90, 95%CI: 0.85-0.95, P<0.001), women who were overweight or obese before pregnancy (FR=0.36, 95%CI: 0.24-0.55, P<0.001), women who were exposed to second-hand smoking (FR=0.63, 95%CI: 0.44-0.92, P=0.016), women whose home or office had been renovated in the past 2 years and had a particular smell (FR=0.46, 95%CI: 0.26-0.81, P=0.008) were risk factors for impaired fertility. Regular menstrual cycles (FR=1.64, 95%CI: 1.16-2.31, P=0.005), females who often drank tea/coffee (FR=1.55, 95%CI: 1.11-2.17, P=0.011) and males who took folic acid before conception (FR=2.35, 95%CI: 1.38-4.23, P=0.002) were associated with better fertility. The cumulative pregnancy rate of 3, 6, and 12 menstrual cycles was 37.6%, 64.4%, and 78.4%, respectively. Conclusion: Older couples, overweight or obesity before pregnancy, irregular menstruation, exposure to secondhand smoke and decoration pollutants in females are associated with impaired fertility. Frequent tea/coffee drinking before pregnancy in females and taking folic acid before pregnancy in males are associated with shortened conception time.

[Clinical analysis of 23 cases with simultaneous double primary gynecological malignant tumors].

Objective: To investigate the clinicopathological features, diagnosis, treatment and prognosis of simultaneous double primary gynecological malignant tumors. Methods: A total of 23 patients with simultaneous double primary malignant tumors of female reproductive system primarily treated in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 1, 2010 to December 31, 2020 were retrospectively collected. The age, symptoms, tumor stage, tumor type, treatment and prognosis of patients were collected and followed up. Results: (1) The number of patients with gynecological tumors in our hospital increased year by year in the past 11 years. A total of 8 987 patients with gynecological malignant tumors were firstly diagnosed and cured in our hospital, including 3 474 cases of cervical cancer, 3 484 cases of endometrial cancer, 1 329 cases of ovarian malignancies, 171 cases of fallopian tube cancer, 182 cases of uterine sarcoma, 42 cases of vaginal cancer, 192 cases of vulvar cancer, 110 cases of trophoblastic tumor and 3 cases of other gynecological malignancies. The top three cancers were endometrial cancer, cervical cancer and ovarian malignancies. (2) There were 23 patients identified with simultaneous double primary gynecological tumors in the past 11 years, accounting for 0.26% (23/8 987) of female malignant tumors. There were 3 cases of cervical cancer complicated with endometrial cancer, 3 cases of cervical cancer complicated with ovarian cancer, 16 cases of endometrial cancer combined with ovarian cancer, and 1 patient with endometrial cancer combined with fallopian tube cancer. (3) All 23 patients underwent surgical treatment. According to the first diagnosis of the tumor, the surgical methods included cervical cancer radical surgery, endometrial cancer staging surgery and ovarian cancer cytoreductive surgery. After operation, radiotherapy and chemotherapy were supplemented according to the results of pathological examination and tumor staging. (4) The age of 23 patients ranged from 28 to 66 years, with an average age of (49.4±9.7) years. All patients had vaginal bleeding or conscious pelvic mass as their main clinical manifestation. The clinical stage was found in 7 patients (30%, 7/23) with advanced gynecological cancer (stage Ⅲ-Ⅳ), and 16 patients (70%, 16/23) with early stage gynecological cancer (stage Ⅰ-Ⅱ). According to the nonspecific tumor markers, 13 patients (57%, 13/23) had elevated CA125 and CA199. (5) Among the 23 patients, 1 case was uncontrolled and 3 cases recurred during the follow-up period, and the sites of uncontrolled or recurred were all located in the abdominopelvic cavity. Three cases died. Among the 3 patients who died, 1 patient was an uncontrolled patient, whose tumor type was cervical adenosquamous cell carcinoma combined with ovarian clear cell adenocarcinoma. The overall survival time was 19 months with postoperative supplementary radiotherapy and chemotherapy. There were 2 recurrent patients, and the tumor types were endometrioid carcinoma complicated with high-grade serous ovarian carcinoma and ovarian endometrioid carcinoma, respectively. After surgery, all patients received supplementary chemotherapy and recurred 60 and 21 months after surgery, respectively, and the overall survival time was 78 and 28 months, respectively. Another patient recurred 43 months after surgery, and survived with tumor for 14 months after recurrence. The remaining 19 patients were tumor-free and were still being followed up. Conclusions: There are no specific markers for simultaneous double primary gynecological malignant tumors. The most common clinical symptoms are vaginal bleeding or pelvic mass. The treatment principle of simultaneous double primary gynecological malignant tumor is the same as that of single gynecological malignant tumor, but need to be taken into account the characteristics of two tumors. Surgery is the main treatment method, and radiotherapy and chemotherapy play an important auxiliary role. The prognosis of simultaneous double primary gynecological malignancies is related to the late stage of the two malignancies.

[Association between the presence of solid or micropapillary components and survival outcome in stage â A lung adenocarcinoma cases: a retrospective cohort study].

Objectives: To examine the influence of the proportion of pathological subtypes on the prognosis of stage ⅠA lung adenocarcinoma cases, and to explore the association between the presence/absence of solid or micropapillary (S/M) components and survival outcome. Methods: Totally 321 patients with stage ⅠA lung adenocarcinoma who received complete surgical resection at Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital from January 2011 to December 2013 were retrospectively analyzed. There were 130 males and 191 females, aging 59(11) years (M(IQR)) (range: 55 to 66 years). The diagnostic value of the proportion of each pathological growth subtype on relapse-free survival (RFS) and overall survival (OS) were analyzed by using receiver operator characteristic curve. Patients were firstly divided into two groups according to the presence or absence of S/M components. And patients without S/M components were farther divided into two groups according to predominant growth pattern. There were three groups in total: with S/M components (group S/M+), without S/M components and lepidic growth pattern predominant (group S/M-LPA), without S/M components and papillary or acinar growth pattern predominant (group S/M-P/A). Kaplan-Meier method were used to draw the survival curves of the three groups, and Log-rank test were used to compare RFS and OS among the three groups. Cox proportional risk model was used to verify whether the presence of S/M components was a prognostic factor on RFS. Results: The proportion of S/M components had no diagnostic value for recurrence (solid: area under curve (AUC)=0.588, P=0.095; micropapillary: AUC=0.566, P=0.106) and death (AUC=0.589, P=0.104; AUC=0.607, P=0.056). The 5-year RFS rate of group S/M-LPA, S/M-P/A and S/M+ were 92.4%, 82.3% and 77.3%, respectively (all P<0.05), while the 5-year OS rate were 97.4%, 94.5% and 83.2%, respectively (all P<0.05). Multivariable analysis showed that the 3 groups were independent predictors of recurrence (S/M-P/A vs. S/M- LPA: HR=2.691, 95%CI: 1.249 to 5.799, P=0.011; S/M+ vs. S/M-LPA, HR=6.763, 95%CI: 3.050 to 14.996, P<0.01). Conclusions: The proportion of S/M components in stage ⅠA lung adenocarcinoma with complete resection cases did not affect survival outcome. New grouping method based on the presence or absence of S/M components were significantly associated with patient survival outcomes: S/M+ patients had the worst prognosis and S/M-LPA patients had the best prognosis.

Monitoring of lung malignant epithelial cells by gene methylation analysis in the conditionally reprogrammed cell cultures.

Conditionally reprogrammed cell (CRC) technology is an effective method for culturing primary malignant cells and non-malignant epithelial cells in vitro. This can be useful for precision medicine applications, such as drug sensitivity assays. However, this approach is commonly hindered by the non-specific growth of non-malignant epithelial cells in CRC cultures and the lack of effective biomarkers/assays to distinguish them from primary tumor cells. In this study, we developed a DNA methylation-based, real-time PCR assay to investigate SHOX2 and PTGER4 gene promoters as sensitive markers for human lung cancer. We first found that in formalin-fixed, paraffin-embedded (FFPE) malignant lung samples, 90% (28/31) had increased SHOX2 and/or PTGER4 promoter methylation as compared with their adjacent non-malignant samples. We then applied this assay to fresh surgical tumors and found increased SHOX2 and/or PTGER4 promoter methylation in 80% (20/25) of tumor samples as compared with their corresponding adjacent non-malignant tissues. Increased methylation of SHOX2 or PTGER4 promoter regions was also detected in 52% (13/25) of CRC cultures. The presence of malignant cells was confirmed by growth in soft agar cultures, a hallmark of malignant transformation, as well by EGFR mutation analysis. These results demonstrate that SHOX2 and PTGER4 promoter methylation levels can be used to detect malignant lung epithelial cells in CRC cultures.

Parenchymal hyperdensity on C-arm CT images after endovascular therapy for acute ischaemic stroke predicts a poor prognosis.

AIM: To investigate whether hyperdense areas (HDAs) observed after endovascular treatment on multisection computed tomography (CT) are related to outcome. MATERIALS AND METHODS: Data on 82 patients with acute anterior circulation ischaemic stroke resulting from intracranial large artery occlusion were analysed retrospectively All patients underwent mechanical thrombectomy and/or emergency angioplasty, and partial or complete recanalisation was successfully achieved. C-arm CT was performed immediately after endovascular treatment for all patients. Clinical and radiological data were compared between patients with and those without HDA and between patients with good and those with poor outcomes. RESULTS: Compared with non-HDA patients, HDA patients were more likely to present with severe neurological deficits (admission National Institutes of Health Stroke Scale [NIHSS] score: 18 versus 16, p=0.037) and had a higher number of stent retriever passes performed (2.9±1.3 versus 1.4±1, p<0.001), longer onset-to-presentation times (229±78 versus 171±90 minutes; p=0.002), longer onset-to-recanalisation times (418±94 versus 331±105 minutes; p<0.001), and longer puncture-to-recanalisation times (103±47 versus 69±42 minutes; p=0.001). Fewer HDA patients had a good prognosis (35.7% versus 70%, p<0.001). Multivariate analysis showed the presence of HDAs was an independent negative prognostic factor (OR=0.208; p=0.002). CONCLUSION: HDAs on C-arm CT appear to be common in patients with acute ischaemic stroke who underwent successful endovascular treatment. HDA presence suggests a poor prognosis despite successful reperfusion.

Redefining Humicola sensu stricto and related genera in the Chaetomiaceae.

The traditional concept of the genus Humicola includes species that produce pigmented, thick-walled and single-celled spores laterally or terminally on hyphae or minimally differentiated conidiophores. More than 50 species have been described in the genus. Species commonly occur in soil, indoor environments, and compost habitats. The taxonomy of Humicola and morphologically similar genera is poorly understood in modern terms. Based on a four-locus phylogeny, the morphological concept of Humicola proved to be polyphyletic. The type of Humicola, H. fuscoatra, belongs to the Chaetomiaceae. In the Chaetomiaceae, species producing humicola-like thick-walled spores are distributed among four lineages: Humicola sensu stricto, Mycothermus, Staphylotrichum, and Trichocladium. In our revised concept of Humicola, asexual and sexually reproducing species both occur. The re-defined Humicola contains 24 species (seven new and thirteen new combinations), which are described and illustrated in this study. The species in this genus produce conidia that are lateral, intercalary or terminal on/in hyphae, and conidiophores are not formed or are minimally developed (micronematous). The ascospores of sexual Humicola species are limoniform to quadrangular in face view and bilaterally flattened with one apical germ pore. Seven species are accepted in Staphylotrichum (four new species, one new combination). Thick-walled conidia of Staphylotrichum species usually arise either from hyphae (micronematous) or from apically branched, seta-like conidiophores (macronematous). The sexual morph represented by Staphylotrichum longicolleum (= Chaetomium longicolleum) produces ascomata with long necks composed of a fused basal part of the terminal hairs, and ascospores that are broad limoniform to nearly globose, bilaterally flattened, with an apical germ pore. The Trichocladium lineage has a high morphological diversity in both asexual and sexual structures. Phylogenetic analysis revealed four subclades in this lineage. However, these subclades are genetically closely related, and no distinctive phenotypic characters are linked to any of them. Fourteen species are accepted in Trichocladium, including one new species, twelve new combinations. The type species of Gilmaniella, G. humicola, belongs to the polyphyletic family Lasiosphaeriaceae (Sordariales), but G. macrospora phylogenetically belongs to Trichocladium. The thermophilic genus Mycothermus and the type species My. thermophilum are validated, and one new Mycothermus species is described. Phylogenetic analyses show that Remersonia, another thermophilic genus, is sister to Mycothermus and two species are known, including one new species. Thermomyces verrucosus produces humicola-like conidia and is transferred to Botryotrichum based on phylogenetic affinities. This study is a first attempt to establish an inclusive modern classification of Humicola and humicola-like genera of the Chaetomiaceae. More research is needed to determine the phylogenetic relationships of "humicola"-like species outside the Chaetomiaceae.

[Evaluation of clinical outcomes of allogeneic hematopoietic stem cell transplantation for relapsed/refractory peripheral T-cell lymphoma with chemoresistance].

Objective: To evaluate the clinical outcomes in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who had undergone allogeneic hematological stem cell transplantation (allo-HSCT). Methods: From June 2007 to June 2017, the clinical data of PTCL patients who underwent HSCT from eight hospitals were assessed retrospectively. Results: There were 23 patients diagnosed as relapsed or refractory PTCL with chemoresistance who underwent allo-HSCT. Among these patients, 18 were identified as progressive disease (PD) status and 5 patients as stable disease (SD) status before allo-HSCT. Seventeen patients received allo-HSCT from matched sibling donor (MSD),2 patients from matched unrelated donor and 4 patients from related haplo-identical donor (HD). After a median follow-up of 29 months, 21 patients survived longer than 28 days after allo-HSCT. Hematopoietic reconstitution was achieved in 20 of the 21 patients. The median time of myeloid and platelet engraftment were+13 (9-22) d and+16(10-38) d, respectively. The 100-d treatment-related mortality rate was 13.1%. Acute GVHD occurred in 11(47.8%) patients at a median time of 22(6-82) d after transplantation. Grade Ⅱ~Ⅳ aGVHD occurred in 6 patients. Chronic GVHD occurred in 10 patients at a median of 7.9 (3.5-27) months. After a median follow-up of 29 months, 13 patients died after HSCT. Four of them died of complications associated with allo-HSCT, and other 9 patients died of the primary lymphoma. The 3-years cumulative overall survival (OS) and progress-free survival (PFS) were 43.03% (95%CI: 29.79-69.16) and 39.13% (95%CI: 23.50-65.14), respectively. No significant difference was found in the 3-year PFS between patients with PD status and SD status before allo-HSCT (P=0.133). Conclusion: Allo-HSCT can be a promising treatment for relapsed or refractory PTCL with chemoresistance.

[Natural changes of high-risk HPV in women with negative for intraepithelial lesion or malignancy: a prospective 1 year study].

Objective: To investigate the natural changes of high-risk HPV (HR-HPV) in women with negative for intraepithelial lesion or malignancy (NILM) for regulating HR-HPV screening. Methods: Four hundred and thirty-three newly-diagnosed women were enrolled from January 1st, 2015 to December 31, 2015 in Beijing Obstetrics and Gynecology Hospital. The ages of these patients were between 22 and 74 years, the average age was (45±21) years old. Two hundred and sixty-three cases were less than 50 years old, 170 cases were more and equal to 50 years old. One hundred and fifty-six cases were HR-HPV positive, 277 cases were HR-HPV negative. Follow up tests were conducted for all 433 patients, who were screened by ThinPrep cytologic test (TCT) combined with HR-HPV and were diagnosed with NILM, for a period of 1 year (at the 3, 6, 9 and 12 months intervals respectively), if the TCT results are abnormal and the HR-HPV test results are positive, will follow up colposcopy directed cervical biopsy. Results: (1) HR-HPV natural changes: of 156 NILM cases with HR-HPV infection, 42 cases (26.9%, 42/156) turned negative within 3 months, 88 cases (56.4%, 88/156) turned negative within 6 months, 99 cases (63.5%, 99/156) turned negative within 9 months, and 100 cases (64.1%, 100/156) turned negative within 12 months. The negative conversion ratio at 3, 6, 9 and 12 months for women at childbearing age (<50 years) were significantly higher than those at non-childbearing age (≥50 years old; all P<0.05). Of 277 NILM cases without HR-HPV infection, 35 cases (12.6%, 35/277) had new HR-HPV positive infections within 3 months, 70 cases (25.3%, 70/277) had new infections within 6 months, 80 cases (28.9%, 80/277) had new infections within 9 months, and 83 cases (30.0%, 83/277) had new infections within 12 months. The new infections rate at 3, 6, 9 and 12 months for women at childbearing age (<50 years old) were slightly higher than those at non-childbearing age (≥50 years old; all P>0.05). (2) The progress of cervical leision: of 156 NILM cases with HR-HPV positive, no case progressed during 12 months follow-up. Of 277 NILM cases with HR-HPV negative, 4 cases progressed to cervical intraepithelial neoplaisa (CIN) with HR-HPV infection and TCT abnormal during 12 months follow-up, including 2 cases pathology diagnosed with CINⅠ, 1 case with CINⅡ, and 1 case with CINⅢ. The progression rate was 1.4%(4/277), which accounts for 4.8% (4/83) of new HR-HPV infections cases in women. Conclusions: The results of cytology combined with HR-HPV screenings suggest every 6 months for simple HR-HPV positive women, colposcopy directed cervical biopsy is recommended to assess cervical lesions if necessary. Cytology combined with HR-HPV screenings suggest every 12 months for simple HR-HPV negative women to early detection of cervical leision.

Systemic inflammation induces anxiety disorder through CXCL12/CXCR4 pathway.

It is evidenced that inflammation is involved in the pathogenesis of anxiety disorder, as well as the dysfunction of glutamate neurotransmission in the central nervous system (CNS). Chemokine CXCL12 has been reported taking part in the regulation of neurotransmitter release, however, the roles of CXCL12 in the development of anxiety are still unclear. In this study, we found that intraperitoneal (i.p) injection of lipopolysaccharide (LPS) induced anxiety-like behaviors in adult mice as measured by elevated plus-maze test (EPM) and open field test (OFT). Astrocytes were responsible for CXCL12 induction upon LPS challenge in hippocampus and amygdala, and microinjection of CXCL12 into amygdala induced mice anxiety-like behaviors. AMD3100, which is an antagonist for CXCL12 receptor CXCR4, prevented the anxiety behaviors induced by microinjection of CXCL12 into amygdala as well as injection i.p of LPS. Knockdown of CXCR4 expression in neurons using short hairpin RNAs (shRNAs) significantly blocked anxiety behaviors mediated by CXCL12 i.c injection. Furthermore, AMD3100 or shCXCR4 prevented the impairment of nesting ability induced by CXCL12 in mice. Whole-cell patch-clamp recordings in the neurons of basolateral amygdala (BLA) revealed that CXCL12 enhanced glutamatergic transmission by increasing sEPSC frequency in the amygdala. AMD3100 inhibited the excitatory glutamatergic neural transmission and involved in the development of anxiety through CXCR4. These findings provide direct evidence that alterations of CXCL12 in BLA play critical roles in the development of anxiety induced by systemic inflammation and that CXCR4 may be a potential therapeutic target for inflammation-induced anxiety.

Placental site trophoblastic tumor: A review of 108 cases and their implications for prognosis and treatment.

OBJECTIVE: To identify important prognostic factors and optimized treatment strategies through the analysis of the clinical and pathological characteristics of placental site trophoblastic tumor. METHODS: 108 patients with PSTT registered in two GTD centers or in six tertiary hospitals in China were analyzed retrospectively between the years 1998 and 2013. The computerized database of clinical and pathological reports was reviewed on this patient group. The data were subsequently analyzed retrospectively using SPSS software. RESULTS: Among 3581 patients with GTNs treated in GTD centers or in the tertiary hospitals between 1998 and 2013, 108 cases were histologically confirmed PSTT (3%). Only seven deaths and eleven relapse cases were observed. All seven of the deaths were disease related, due to chemotherapy-resistant or relapsed. 23 patients who received fertility preservation treatment did not experience poor outcome or high risk of relapse. In 71 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I disease, the use of adjuvant chemotherapy following surgery (n=49) or not (n=22) made no significant difference in relapse rate (P=0.303) or survival (P=0.782). Univariate analysis revealed the interval between antecedent pregnancy and onset of PSTT, stage, prognosis score, and necrosis as significant predictors of poor survival but only stage remained significant on multivariate analysis. CONCLUSIONS: Patients with FIGO stage IV disease demonstrate the most critical risk indicator of PSTT in the current study. Preservation of fertility is considered in highly-selected patients with localized tumor; and surgery without chemotherapy is recommended as first line treatment for patients with stage I who are at low-risk.

[Clinico-pathological characteristics and prognosis of IgA nephropathy patients with microalbuminuria and deposition of complement C3].

OBJECTIVE: To analyze the clinical and pathological data and prognosis of IgA nephropathy patients with microalbuminuria and deposition of C3, and to investigate the significance of C3 deposition in IgA nephropathy with microalbuminuria. METHODS: The clinical and pathological data of 127 IgA nephropathy patients with microalbuminuria confirmed by renal biopsy in the Jining No.1 People's Hospital from January 2009 to January 2015 and minimum 6-month follow-up was reviewed, and patients were divided into positive group (72 cases, 56.7%)and negative group (55 cases, 43.3%) according to the deposition of C3 in the mesangial area of glomeruli. 24 h urine quantitative protein being more than 1 g, or serum creatinine level becoming abnormal or double by renal biopsy was defined as endpoint of follow-up. Renal survival was calculated by Kaplan-Meier survival analysis. RESULTS: A total of 127 IgA nephropathy patients with microalbuminuria were followed up successfully, with an average follow-up of (49.6±22.7) months. 24 h urine albumin[(261.3±47.4) vs (238.7±51.9) mg, P=0.011], serum creatinine value[98.0(56.4, 118.6) vs 85.7(51.9, 107.8) µmol/L, P=0.003], uric acid value[(384.0±93.7) vs (360.5±88.4) µmol/L, P=0.043] and serum IgA value[(3.36±1.17) vs (3.12±1.05) g/L, P=0.044] were significantly higher in the C3 positive group than those in the negative group, while the serum complement C3 was significantly lower [(0.70±0.42) vs (0.98±0.49) mg, P=0.047]. Pathological changes [Lee's grade Ⅲ and above Ⅲ: 21(16.5%) vs 11(8.7%), P=0.034], glomerular sclerosis or adhesions [29(22.8%) vs 19(15.0%), P=0.047], renal tubular atrophy or interstitial fibrosis [13(10.2%) vs 8(6.3%), P=0.027] and crescent formation [7(5.5%) vs 2(1.6%), P=0.035] in the complement C3 positive group were more severe than those in the negative group. 38 cases of complement C3 positive group and 14 cases of negative group accomplished the study, and Kaplan-Meier survival analysis showed that there was a significant difference in the median survival time between the two groups [(52.6±8.9) vs (66.1±9.7) months, P=0.019]. CONCLUSIONS: The clinical and pathological features in IgA nephropathy patients with microalbuminuria and deposition of complement C3 were more severe than those without complement C3 deposition, and the prognosis was not optimistic. Therefore, early and active intervention treatment should be considered for these patients.

[Analysis on the polymorphisms of human B cell epitopes of 5 specificity antigens in Mycobacterium tuberculosis in China].

OBJECTIVE: To study the diversities of human B cell epitopes of five proteins (Mpt83, Mpt70, LpqH, PstS3, GroES) in Mycobacterium tuberculosis isolates from China. METHODS: We selected 179 strains isolated from patients with tuberculosis in different regions of China, and cultured these strains by L-J medium. The gene sequences of these 5 proteins were amplified and sequenced by PCR. The variations (single nucleotide polymorphisms, SNP) of the DNA sequences were compared and analyzed according to the immune epitope database (IEDB). The synonymous mutation rate (dS), non-synonymous mutation rate (dN) and dN/dS values were calculated with MEGA6 software. RESULTS: Among the 179 clinical MTBC isolates, 7 SNP mutations were found in the mpt83gene. The dN/dS value of the whole mpt83 gene was 0.88. One SNP mutation was found in the mpt70 gene. The dN/dS values of the whole pstS3 gene and non-B epitopes areas were 1.74 and 1.40 respectively. But no mutation was found in the groES gene. CONCLUSION: The mpt83, lpqH and pstS3 genes of 179 MTBC strains contain gene SNPs and human B cell epitopes diversities, while the coding gene and human B cell epitopes of protein mpt70 and groES were conservative.

The association between the RAGE G82S polymorphism, sRAGE and chronic periodontitis in Taiwanese individuals with and without diabetes.

BACKGROUND AND OBJECTIVE: The present study investigated the association between the RAGE G82S polymorphism, the plasma levels of sRAGE and chronic periodontitis in subjects with and without diabetes mellitus (DM). MATERIAL AND METHODS: A total of 230 patients with DM and 264 non-DM participants were recruited for this study. Genotyping of the RAGE G82S polymorphism was accomplished using polymerase chain reaction-restriction fragment length polymorphism, and associations were analyzed with the chi-squared test and logistic regression analysis. RESULTS: In the non-DM group, the chi-squared test showed that the frequency distributions of the G82S polymorphism were significantly different between chronic periodontitis and non-chronic periodontitis subjects (χ(2) = 8.39, p = 0.02). A multivariate logistic regression model showed that the (G82S + S82S) genotypes were associated with a significantly increased risk of chronic periodontitis development compared to the G82G genotype (adjusted odds ratio = 2.06, 95% confidence interval: 1.08-4.07). In the DM group, there was no association between the G82S polymorphism and chronic periodontitis development when a multivariate logistic regression was performed. Plasma levels of sRAGE were significantly higher in subjects with the G82G genotype compared to those with the (G82S + S82S) genotypes in both the non-DM (856.6 ± 332.0 vs. 720.4 ± 311.4 pg/mL, p = 0.003) and DM groups (915.3 ± 497.1 vs. 603.5 ± 298.3 pg/mL, p < 0.0001). However, there was no difference in plasma sRAGE levels between chronic periodontitis and non-chronic periodontitis subjects in both the DM and non-DM groups. Moreover, when the subjects were further sub-divided by the G82S polymorphism, the difference in plasma levels of sRAGE between chronic periodontitis and non-chronic periodontitis subjects in the DM and non-DM groups remained statistically insignificant. CONCLUSIONS: The present study revealed that the RAGE G82S polymorphism was associated with chronic periodontitis in the non-DM group but not in the DM group. Our results also showed that the plasma levels of sRAGE were significantly higher in subjects with the RAGE G82G genotype, and this correlation was not affected by the presence of chronic periodontitis in the DM and non-DM groups.

Expressions of survivin, P16(INK4a), COX-2, and Ki-67 in cervical cancer progression reveal the potential clinical application.

PURPOSE OF INVESTIGATION: To explore the significance of survivin, P16(INK4a), COX-2, and Ki-67 expressions for prediction of cervical cancer progression. MATERIALS AND METHODS: A retrospective study was performed in 129 cases including 24 squamous carcinoma of the cervix (SCC), 70 cervical intraepithelial neoplasias (CIN), 15 cervical condyloma acuminatum (CCA), ten chronic cervicitis (CC), and ten normal cervix (NC). Protein expressions were evaluated using immunohistochemistry. RESULTS: Survivin, P16(INK4a); COX-2, and Ki-67 were highly expressed in SCC and CIN compared with others. Their expression rates were gradually increased in CIN I, CIN II, CIN III, and SCC groups, showing 72.00%, 88.00%, 90.00%, and 95.83% for P16(INK4a), 68.00%, 84.00%, 95.00% and 100.00% for COX-2, 76.00%, 96.00%, 100.00%, and 100.00 for Ki-67, respectively. There were significant correlations between survivin and P16(INK4a), COX-2, Ki-67, as well as P16(INK4a) and Ki-67. CONCLUSION: Survivin, P16(INK4a), COX-2 and Ki-67 play critical roles for development and progression of cervical cancer.

Effects of phenylalanine and threonine oligopeptides on milk protein synthesis in cultured bovine mammary epithelial cells.

This study was conducted to investigate the effects of phenylalanine (Phe) and threonine (Thr) oligopeptides on αs1 casein gene expression and milk protein synthesis in bovine mammary epithelial cells. Primary mammary epithelial cells were obtained from Holstein dairy cows and incubated in Dulbecco's modified Eagle's medium-F12 medium (DMEM/F12) containing lactogenic hormones (prolactin and glucocorticoids). Free Phe (117 µg/ml) was substituted partly with peptide-bound Phe (phenylalanylphenylalanine, phenylalanyl threonine, threonyl-phenylalanyl-phenylalanine) in the experimental media. After incubation with experimental medium, cells were collected for gene expression analysis and medium was collected for milk protein or amino acid determination. The results showed that peptide-bound Phe at 10% (11.7 µg/ml) significantly enhanced αs1 casein gene expression and milk protein synthesis as compared with equivalent amount of free Phe. When 10% Phe was replaced by phenylalanylphenylalanine, the disappearance of most essential amino acids increased significantly, and gene expression of peptide transporter 2 and some amino acid transporters was significantly enhanced. These results indicate that the Phe and Thr oligopeptides are important for milk protein synthesis, and peptide-bound amino acids could be utilised more efficiently in milk protein synthesis than the equivalent amount of free amino acids.

PTEN inactivation by germline/somatic c.950_953delTACT mutation in patients with Lhermitte-Duclos disease manifesting progressive phenotypes.

Lhermitte-Duclos disease (LDD), a neurological manifestation of Cowden syndrome (CS), is a rare and benign cerebellar disorder, featured by dysplastic cerebellar ganglion cells which replace granular and Purkinje cells. Phosphatase and Tensin Homolog (PTEN) is confirmed as the susceptibility gene for CS which represents the most complex features and is not easily recognizable. We reported two index patients with LDD diagnosed either in an isolated form or coexist with CS. These two patients displayed progressive though comparable phenotypes and were found to carry an identical PTEN c.950_953delTACT mutation in either germline or somatic sources of DNA, respectively. Negative or moderate expression levels of PTEN were validated by immunohistochemistry in the corresponding patients' affected tissues. This study has revealed a novel pathogenicity locus to LDD/CS as a candidate for early molecular diagnosis. In addition, the differential PTEN mutation status with corresponding LDD phenotypes suggests a potential correlation between germline or somatic mutation and coexisting LDD/CS or isolated LDD, respectively. Furthermore, our data could lend some reference to the underlying molecular mechanism of LDD pathogenesis in the future.

Effects of alfalfa and cereal straw as a forage source on nutrient digestibility and lactation performance in lactating dairy cows.

This study was conducted to investigate the nutrient digestibility and lactation performance when alfalfa was replaced with rice straw or corn stover in the diet of lactating cows. Forty-five multiparous Holstein dairy cows were blocked based on days in milk (164 ± 24.8 d; mean ± standard deviation) and milk yield (29.7 ± 4.7 kg; mean ± standard deviation) and were randomly assigned to 1 of 3 treatments. Diets were isonitrogenous, with a forage-to-concentrate ratio of 45:55 [dry matter (DM) basis] and contained identical concentrate mixtures and 15% corn silage, with different forage sources (on a DM basis): 23% alfalfa hay and 7% Chinese wild rye hay (AH), 30% corn stover (CS), and 30% rice straw (RS). The experiment was conducted over a 14-wk period, with the first 2 wk for adaptation. The DM intake of the cows was not affected by forage source. Yield of milk, milk fat, protein, lactose, and total solids was higher in cows fed diets of AH than diets of RS or CS, with no difference between RS and CS. Contents of milk protein and total solids were higher in AH than in RS, with no difference between CS and AH or RS. Feed efficiency (milk yield/DM intake) was highest for cows fed AH, followed by RS and CS. Cows fed AH excreted more urinary purine derivatives, indicating that the microbial crude protein yield may be higher for the AH diet than for RS and CS, which may be attributed to the higher content of fermentable carbohydrates in AH than in RS and CS. Total-tract apparent digestibilities of all the nutrients were higher in cows fed the AH diet than those fed CS and RS. The concentration of rumen volatile fatty acids was higher in the AH diet than in CS or RS diets, with no difference between CS and RS diets. When the cereal straw was used to replace alfalfa as a main forage source for lactating cows, the shortage of fermented energy may have reduced the rumen microbial protein synthesis, resulting in lower milk protein yield, and lower nutrient digestibility may have restricted milk production.