Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses. Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann-Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes. Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy. Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

Objective:To investigate potential mechanisms of Niclosamide,a calcium-binding protein S100A4 inhibitor,in regulating inflammatory response of bronchial epithelial cells.Methods:Human bronchial epithelial cells BEAS-2B were cultured in vitro and stimulated by LPS or Niclosamide-pretreatment.Inflammatory cytokines and potential signaling molecules expressions were determined by RT-qPCR and Western blot.Intracellular ROS level was quantified by fluorescent probe.Results:Increased ROS level was observed in LPS-stimulated and Niclosamide-pretreatment cells(P<0.05).Compared with control group,mRNA and protein expressions of S100A4 were increased(P<0.05),TLR4/STAT3,MAPK1/3/SIRT1,NF-κB/IKKβ/p65 mRNA expressions were increased(P<0.05),inflammatory cytokines IL-1β and IL-6,tight junction Occludin and ZO-1 mRNA expressions were increased after LPS-treatment(P<0.05),whereas these genetic expressions were downregulated by Niclosamide-pretreatment(P<0.05),except for TLR4/MAPK1 and NF-κB/IKKβ/p65(P>0.05).Western blot showed that compared with control group,LPS-stimulation promoted protein expressions of S100A4,STAT3,MAPK3/SIRT1,IL-1β and TNF-α(P<0.05),while downregulated protein expression of Occludin.Compared with LPS group,niclosamide-pretreatment downregulated protein expressions of S100A4,STAT3,MAPK3/SIRT1,IL-1β and TNF-α(P<0.05),while restored protein expression of Occludin(P<0.05).Conclusion:Calcium-binding protein S100A4 inhibitor Niclosamide can alleviate S100A4 expression and inflammatory response of bronchial epithelial cells,which is poten-tially related to STAT3 or MAPK3/SIRT1 signaling.

OBJECTIVES: With the increase in aging population in China, elderly Crohn's disease (CD) patients need to receive more attention. This study aims to explore the clinical characteristics and disease process of elderly onset CD (EOCD) patients in a single center. METHODS: From January 2002 to January 2022, a total of 221 patients with CD from the Seventh Medical Center of Chinese PLA General Hospital were enrolled. According to the Montreal CD classification standard, the patients were further divided into 4 groups: an EOCD group (≥60 years old, n=25), a middle age onset CD (MOCD) group (40-59 years old, n=46), a young onset CD (YOCD) group (17-40 years old, n=131), and a childhood onset CD (COCD) group (6-16 years old, n=19). We compared the clinical characteristics and long-term prognosis among them. RESULTS: Females were predominant in the EOCD group (15/25, 60%). The number of people without smoking in the EOCD group (80%) was lower than that in COCD group (100%), higher than that in the YOCD group (70.2%) and the MOCD group (69.6%) (all P<0.05). Patients with perianal diseases at diagnosis were rare in the EOCD group (0%), lower than that in the COCD group (21.1%) and the YOVD group (19.8%) (all P<0.05). Stenosis was the most common disease behavior in the EOCD group (63.0%), significantly higher than that in the COCD group (15.8%), the YOCD group (36.6%) and the MOCD group (43.5%) (all P<0.05). The EOCD group was easier to be misdiagnosed as tumor (24%), higher than that in the COCD group (0%), the YOCD group (6.9%) and the MOCD group (19.6%) (all P<0.05). The EOCD group was prone to comorbidities (52%), and 20% of them were complicated with multiple comorbidities (P<0.05). During the follow-up, the all-cause mortality of EOCD was 12%, and the CD-related mortality was 8%, which was significantly higher than the other groups (all P<0.05). The use of immunosuppressants in the EOCD group (4.8%) was lower than that in the COCD group (12.8%), the YOCD group (16.8%) and the MOCD group (16.1%), but there was no statistical significance among the 4 groups (P=0.467). In addition, there was no significant difference in the rate of intestinal resection among the 4 groups (P=0.062). CONCLUSIONS In EOCD patients, females were predominant, smoking was less common, and they were prone to comorbidity. At the initial stage of diagnosis, it is easy to be misdiagnosed as tumor, and the disease behavior mainly showed stricture type, less complicated with perianal diseases. During the follow-up, all-cause mortality and CD-related mortality of EOCD patients were significantly higher than those of the non-elderly onset CD patients.
Female ; Middle Aged ; Humans ; Aged ; Child ; Adult ; Adolescent ; Young Adult ; Crohn Disease/epidemiology* ; Prognosis ; Constriction, Pathologic ; Aging ; Hospitals, General

Objective:To prospectively follow up the patients with ileocecal inflammatory lesions, to explore the characteristics of Crohn′s disease(CD) at early stage, and to provide references for early diagnosis of CD.Methods:From January 2013 to December 2018, at Department of Gastroenterology, The Seventh Medical Center of PLA General Hospital, 232 patients with unexplained ileocecal inflammatory lesions under colonoscopy examination were enrolled, which were followed up for more than one year. Chi-square test and Fisher exact probability text were used to compare the patients with early CD, with non-specific enteritis and intestinal tuberculosis in abdominal symptoms (abdominal pain, diarrhea, abdominal distension, constipation, hematochezia, changes in bowel habits), accompanying symptoms (oral ulcer, arthralgia), the proportion of patients with elevated erythrocyte sedimentation rate (ESR) or elevated C-reactive protein (CRP) level, serum antineutrophilic cytoplasmic antibody (ANCA), anti-saccharomyces cerevisiae antibody (ASCA), tuberculosis infection of T cells spot test, positive rate of fecal occult blood, lesion size, morphology, involvement site under endoscopy and histopathological results. Multivariate binary logistic regression was used to analyze the related factors of early CD.Results:Among 232 patients, 155 were males and 77 were females, and the age of first diagnosis was (43.9±13.8) years old. The follow-up period (range) was 27 months (12 to 79 months). Twenty-nine cases (12.5%) were diagnosed as early CD, 45 cases (19.4%) were intestinal tuberculosis, 105 cases (45.3%) were non-specific enteritis, and 53 cases (22.8%) as undetermined. All of 29 patients with early CD had abdominal symptoms, which accounted for 16.9% (29/172) of 172 patients with ileoceccal inflammatory lesion as well as abdominal symptoms. In early CD patients, the proportions of patients with abdominal pain, elevated CRP level and ESR level, positive rate of ASCA, positive rate of tuberculosis infection T cells and percentage of patients with thickened intestinal wall were all higher than those in patients with non-specific enteritis (62.1%, 18/29 vs. 33.3%, 35/105; 13.8%, 4/29 vs. 0; 13.8%, 4/29 vs. 1.0%, 1/105; 24.1%, 7/29 vs. 1.0%, 1/105; 20.7%, 6/29 vs. 3.8%, 4/105; 95.7%, 22/23 vs. 0), and the proportion of patients without abdominal symptoms was lower than that of patients with non-specific enteritis (0 vs. 31.4%, 33/105). And the differences were statistically significant ( χ2=6.692, Fisher exact probability text, χ2=7.162, χ2=17.826, χ2=7.497, Fisher exact probability text, and Fisher exact probability text, all P<0.05). Early CD patients were more likely to have multiple lesion sites (55.2%, 16/29), and mainly deep ulcers (55.2%, 16/29) and ulcers with a long diameter of 5 to 10 mm (39.3%, 11/28). The lesions of non-specific enteritis were mostly confined to the end of ileum (75.2%, 79/105), which were mainly superficial ulcers (41.0%, 43/105) and ulcers with a long diameter less than 5 mm (69.0%, 49/71). The proportion of patients without abdominal symptoms and the positive rate of tuberculosis infection of T cells spot test of early CD patients were both lower than those of intestinal tuberculosis group (0 vs. 15.6%, 7/45 and 20.7%, 6/29 vs. 68.9%, 31/45). The positive rate of ASCA and the proportion of patients with thickened intestinal wall were higher than those of intestinal tuberculosis group (24.1%, 7/29 vs. 0 and 95.7%, 22/23 vs. 11/19), and the differences were statistically significant (Fisher exact probability text, χ2=13.713, Fisher exact probability text and χ2=6.710, all P<0.05). The results of multivariate binary logistic regression analysis showed that abdominal pain and positive ASCA were independent risk factors for early CD (odds ratio ( OR)=2.855, 95% confidence interval ( CI) 1.014 to 8.037, P=0.047; OR=10.033, 95% CI 2.274 to 44.250, P=0.002). Conclusions:Prospective follow-up for more than one year in patients with unexplained ileocecal inflammatory lesions can effectively identify and diagnose early CD. Ileocecal inflammatory lesions with abdominal symptoms are one of the early manifestations of CD. Abdominal pain and positive serum ASCA at the initial diagnosis are independent risk factors for early diagnosis of CD.

Cosmetic and plastic surgery of female external genitalia is a new subject which adopts surgical or non-surgical methods to rectification of vulva and vagina.With the social progress, genitalia plastic surgery has also achieved a dramatic of development, various new technologies has been applied, and women’s genitalia plastic surgery has shown a good prospect. This review focuses on new concepts and techniques of surgery and non-surgical cosmetic surgery of female external genitalia, including the surgical methods, such as mons pubic plasty, clitoral hood plasty, labia minora reduction surgery, labia majora reduction surgery, labia majora augmentation surgery, perineoplasty, vaginoplasty, and non-surgical methods like G-spot augmentation, orgasm shot therapy, photoelectricity-energy based therapy, etc. It could help plastic surgeons and gynecologists to understand the concepts and therapeutics better in this field.

Cosmetic and plastic surgery of female external genitalia is a new subject which adopts surgical or non-surgical methods to rectification of vulva and vagina.With the social progress, genitalia plastic surgery has also achieved a dramatic of development, various new technologies has been applied, and women’s genitalia plastic surgery has shown a good prospect. This review focuses on new concepts and techniques of surgery and non-surgical cosmetic surgery of female external genitalia, including the surgical methods, such as mons pubic plasty, clitoral hood plasty, labia minora reduction surgery, labia majora reduction surgery, labia majora augmentation surgery, perineoplasty, vaginoplasty, and non-surgical methods like G-spot augmentation, orgasm shot therapy, photoelectricity-energy based therapy, etc. It could help plastic surgeons and gynecologists to understand the concepts and therapeutics better in this field.

Objective: To explore the valuable indicators for differential diagnosis by comparing the clinical features of Crohn′s disease (CD) with primary intestinal lymphoma (PIL). Methods: From 2010 to 2017, at The Seventh Medical Center of PLA General Hospital, a total of 91 patients diagnosed with CD or PIL were enrolled, including 76 cases of CD, 14 cases of PIL and one case of CD with secondary lymphoma. The clinical data of enrolled patients were retrospectively analyzed. T-test, non-parametric test and chi-square test were used for statistical analysis. Results: The average age at diagnosis of CD patients was (37.7±16.0) years, which was younger than that of PIL patients (52.6±19.6) years, and the difference was statistically significant (t=-3.085, P=0.003). The median duration of CD was 36.0 months, which was longer than that of PIL (3.5 months), and the difference was statistically significant (Z=-3.616, P<0.01). Abdominal pain and extra-intestinal manifestations (oral ulcers, joint injuries, erythema nodosum and perianal lesions) were more common in CD patients, and the differences were all statistically significant (χ²=9.427 and 5.173, both P<0.05). CD patients were not diagnosed by colonoscopic biopsy alone. Totally 13 of 14 patients were diagnosed by colonoscopic biopsy and immunohistochemisty and one patient was diagnosed after surgery. The diagnostic rate of pathological biopsy in PIL group was significantly higher than that in CD group (χ²=82.584, P<0.01). One patient was initially clinically diagnosed as CD, and then developed secondary lymphoma after five times of infliximab treatment. Conclusions The diagnosis of CD is generally supported by young age, long course of disease, abdominal pain and extra-intestinal manifestations. The diagnostic rate of colonoscopic biospsy in PIL patients is higher than that in CD patients.

Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABC transporter subfamily G member 2 (ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [I]-iodoarylazidoprazosin (IAAP). However, olmutinib neither altered ABCG2 expression at protein and mRNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly, olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

Objective To explore the clinical characters,treatment and prognosis of gastrointestinal Dieulafoy lesion in China.Methods Dieulafoy was used as search term,the literatures about Chinese patients with Dieulafoy lesions from January 1998 to October 2016 were retrieved in the Chinese literature library including China National Knowledge Infrastructure,VIP network,Wanfang database and China Biology Medicine disc,and a total of 515 literatures,5 145 patients were enrolled and analyzed.The gender,age,geographical distribution,location of the lesion,treatment and prognosis of the disease were summarized.Results Among the 5 145 patients (male 3 959,female 1 186) with Dieulafoy disease,the ratio of male to female was 3.34∶1.00.The age was from 3 to 95 years,and mean age was 51 years.The lesion location was mainly in stomach (88.82％,4 570/5 145) and second was small intestine (8.28％,426/5 145).In stomach,the lesions were mainly located in gastric corpus,fundus and cardia.The small intestinal Dieulafoy lesions were mainly located in duodenum.The main manifests were sudden hematemesis,melena,and hematochezia.The treatments mainly was endoscopic treatment (72.56％,3 733/5 145),and second was surgery (25.27％,1 300/5 145).Among the5 145 patients withDieulafoy disease,5 099 patients (99.11％) were cured and 46 patients (0.89％) died.The proportions of endoscopic treatment,interventional therapy and first endoscopic treatment within 24 hours in tertiary hospitals were all higher than those of nontertiary (all P＜0.01).The cure rate of tertiary hospitals (99.22％,3 674/3 793) was significantly higher than that of nontertiary hosptials (98.54％,1 421/1 442) (x2 =0.89,P＜0.05) and the mortality was significantly lower than that of nontertiary hospitals (P＜ 0.05).Conclusions The male is more susceptible to Dieulafoy lesion which occurred at any age than the female in China.The predilection sites of Dieulafoy lesion were stomach and duodenum.The primary treatments were endoscopic treatment and surgery,and the disease usually had a good prognosis.

Objective:To study the correlations between ethics morality, society, psychological cognition and health and disease. Methods:A total of 356 patients were selected to analyze the influence to health and disease from six perspectives that included family ethics, social morality, life style, interpersonal relationship, mental health, and personality traits. Result:Psychosomatic diseases were occurred in 126 cases, and 220 cases of neuro-sis diseases. The disease incidences in the subjects with high cognitive level were significantly lower than those with low cognitive level (P<0. 01). The cognitive levels of family ethics, social ethics, life style, interpersonal rela-tionship, and mental health were closely related to health and disease (P<0. 05). Conclusion:The cognitive lev-els of ethics morality, society, psychology were closely associated with disease. It should be vigorously advocated that the whole society follow the ethics morality standards, to prevent diseases.