[Clinical and pathological analysis of 345 cases of vulvar lichen sclerosus and a preliminary study on the frequency of maintenance treatment].

Objective: To analyze and summarize the clinical and pathological characteristics, management, and efficacy of patients with vulvar lichen sclerosus (VLS) through a single center large sample study, and preliminarily to explore the frequency of maintenance treatment medication for VLS. Methods: The clinical data of VLS patients in Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2021 were retrospectively collected. The clinicopathological characteristics (patients' age, course of disease, complicated disease history, family history, symptoms, signs and pathology), treatment and effects were retrospectively analyzed. The patients in the maintenance treatment stage were followed up regularly to explore the minimum frequency of individual medication to maintain the stability of the disease. Results: (1) General situation: a total of 345 patients with VLS were included in this study. The average age was (50.4±14.7) years (ranged from 8 to 84 years old), prevalence was highest in the 50-59 years group (30.1%, 104/345). Immune diseases occurred in 18.6% (33/177) of patients, 24.3% (43/177) of patients had allergic skin diseases, and 5.6% (10/177) of the patients' immediate family members had chronic vulvar pruritus or vulvar hypopigmentation. (2) Clinical features: the most common symptom was vulvar pruritus (96.1%, 196/204) among 204 patients with recorded symptoms. The most common sign was hypopigmentation of the vulva (96.3%, 206/214). The most common involved sites were labia minora (70.3%, 142/202), labia majora (67.8%, 137/202), and labial sulcus (59.4%, 120/202). The cumulative number of sites involved in 62 vulvar atrophy patients (2.7±1.1) was significantly higher than that in 152 non-atrophy patients (2.2±1.0; t=3.48, P=0.001). The course of vulvar atrophy was (9.3±8.5) years, which was significantly longer than that of non-atrophy patients [(6.6±5.6) years; t=2.04, P=0.046]. (3) Pathological features: among the 286 patients with electronic pathological sections, the most common pathological feature in the epidermis was epithelial nail process passivation (71.3%, 204/286). The common pathological features in the dermis were interstitial collagenization (84.6%, 242/286), and inflammatory cell infiltration (73.8%, 211/286). (4) Treatment: 177 patients received standardized treatment after diagnosis and were followed up regularly in our hospital. In the initial treatment stage, 26.0% (46/177) of the patients were treated with 0.05% clobetasol propionate cream, and 74.0% (131/177) of the patients were treated with 0.1% mometasone furoate ointment. The complete remission rates of the two methods were respectively 80.4% (37/46) and 74.0% (97/131), and there was no statistically significant difference (χ²=0.76, P=0.385). During maintenance treatment, 27.1% (48/177) of the patients took the medication twice a week, 35.0% (62/177) took the medication once a week, and 37.9% (67/177) took the medication once every 10 days. During follow-up after 6 months of maintenance treatment, there were no patients with recurrence of pruritus or progression of vulvar signs. Conclusions: The majority of VLS patients have itching, hypopigmentation, involvement of labia minora and labia majora, progressive atrophy, and inflammatory infiltration of dermis. Local treatments of mometasone furoate and clobetasol propionate have good initial therapeutic effects. The frequency exploration of individualized maintenance treatment could minimize the occurrence of adverse reactions when ensuring the stability of the patients' condition.

A prospective multicentre controlled study of Gaoweikang (Chinese multiherb extract-based tincture) used in high-risk HPV infections.

OBJECTIVE: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs). PATIENTS AND METHODS: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed. RESULTS: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001). CONCLUSIONS: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.

[Detection rate and clinical characteristics of vulvar squamous intraepithelial lesion].

Objective: To explore the detection rate, clinical characteristics of vulvar squamous intraepithelial lesion (SIL). Methods: Women diagnosed with vulvar high-grade squamous intraepithelial lesions (HSIL) through colposcopy-guided biopsy from January 1, 2018 to August 31, 2022 in Obstetrics and Gynecology Hospital of Fudan University were included in a 1∶1 ratio with patients diagnosed with vulvar low-grade squamous intraepithelial lesions (LSIL) during the same period. Clinical characteristics including human papillomavirus (HPV) infection rate, genotype, cytology result, colposcopy impression, and lesion location were retrospectively analyzed. Results: (1) The proportion of vulvar SIL detected by colposcopy-guided biopsy increased annually from 2018 to 2022, with rates of 1.64% (740/45 057), 2.34% (1 110/47 402), 2.68% (1 108/41 335), 3.26% (1 536/47 078), 3.31% (667/20 155), with an average rate of 2.57% (5 161/201 027). (2) A total of 1 096 cases of vulvar HSIL and 1 096 cases of vulvar LSIL were included. The overall infection rate of HPV was 92.7% (1 993/2 150), with higher infection rate in vulvar HSIL patients than that in vulvar LSIL patients [96.0% (1 012/1 054) vs 89.5% (981/1 096); χ2=33.62, P<0.001]. Among vulvar HSIL patients, the common HPV genotype from high to low were HPV 16 (66.7%), HPV 52 (14.3%), and HPV 58 (10.0%). For vulvar LSIL patients, the most common HPV genotype were respectively HPV 16 (24.9%), HPV 6 (20.1%) and HPV 52 (17.1%). The overall sensitivity rate of cytology was 53.6%, with no significance difference between vulvar LSIL and HSIL groups (54.3% vs 52.9%; χ2=0.40, P=0.526). The accuracy of colposcopy impression for vulvar HSIL was lower than that for vulvar LSIL [40.2% (163/405) vs 81.7% (380/465); χ2=158.72, P<0.001]. About 57.3% (1 257/2 192) of the patients had concomitant cervical and vaginal lesions, with a higher rate in vulvar HSIL group than that in vulvar LSIL group [62.6% (686/1 096) vs 52.1% (571/1 096); χ2=24.67, P<0.001]. Unifocal lesion was the main type, with no significance difference between vulvar LSIL and HSIL groups [81.4% (381/468) vs 82.5% (386/468); χ2=0.18, P=0.671]. The most common lesion locations were the posterior commissure, followed by labia minora, vaginal vestibule, labia majora, perianal and clitoris. Conclusions: The detection rate of vulvar SIL under colposcopy is about 3%, and the infection rate of HPV is 92.7%. Vulvar SIL, especially vulvar HSIL, is likely to cause concomitant cervical and vaginal lesions. The accuracy of colposcopy in diagnosing vulvar HSIL is low. Therefore a comprehensive and careful examination of the vulva is necessary and suspicious vulvar lesions should be undergone colposcopy-guided biopsy for diagnosis.

[Stratified research on related risk factors of CINâ ¡+ in CINâ patients diagnosed by endocervical curettage under colposcopy].

Objective: To estimate risks of cervical intraepithelial neoplasia (CIN) Ⅱ or worse (CINⅡ+) on loop electrosurgical excisional procedure (LEEP) specimens with the diagnosis of endocervical curettage (ECC) CINⅠ compared with biopsy CINⅠ, and also to investigate the hierarchical management scheme of ECC CINⅠ based on the relevant factors of CINⅡ+ risk. Methods: (1) A retrospective computer-based research for subjects enrolled in the Obstetrics and Gynecology Hospital, Fudan University from Jan. 2013 to Jun. 2021 was performed. The case group comprised women with an ECC CINⅠ (ECC results of CINⅠ with colposcopy-directed biopsy results ≤CINⅠ), and the control group comprised women with a biopsy CINⅠ (colposcopy-directed biopsy results of CINⅠ with negative ECC findings) were divided after LEEP surgery and diagnosis in the next three months. The clinical data of all patients before LEEP were analyzed, and the pathological diagnosis between two groups after LEEP was compared. (2) Variables, including age, cytology, high-risk human papillomavirus (HR-HPV), ECC results, cervical transformation zone (TZ) and colposcopy impression, were included to describe the characteristics and compare the incidence of LEEP CINⅡ+. (3) Univariate analysis and Multivariate logistic regression method were used to analyze the related factors that affect the LEEP CINⅡ+ in CINⅠ patients. Further, the specific risks caused by related factors and conduct a stratified study in LEEP CINⅡ+ were analyzed. Results: (1) Overall, 2 581 women with ECC CINⅠ or biopsy CINⅠ diagnosis who underwent LEEP participated in the study with the mean age (43.6±9.5) years old. Chi square test found that the age and cytology of patients in ECC CINⅠ group were statistically different from those of biopsy CINⅠ group (all P<0.05). There was no significant difference in HR-HPV detection, TZ type and colposcopy impression between the two groups (all P>0.05). ECC CINⅠ comprised 957 women, with LEEP histopathology results revealing 288 (30.1%, 288/957) CINⅡ+, which was significantly higher than that of biopsy CINⅠ which was comprised 1 624 women, with LEEP histopathology results showing 333 (20.5%, 333/1 624) CINⅡ+ (χ2=30.31, P<0.001). (2) Compared by LEEP CINⅡ+ with LEEP ≤CINⅠ group, there were no significant difference in the age, HR-HPV, colposcopy impression (all P>0.05); but there were significantly differences in cytology, ECC CINⅠ, type Ⅲ TZ (all P<0.001). Multivariate logistic regression analysis showed that atypical squamous epithelial cells (ASC-H; OR=2.77, 95%CI: 2.04-3.77), high-grade squamous intraepithelial lesions and worse (HSIL+; OR=2.93, 95%CI: 2.24-3.81), ECC CINⅠ (OR=1.89, 95%CI: 1.56-2.29) and type Ⅲ of TZ (OR=1.76, 95%CI: 1.45-2.11) were independent risk factors for LEEP CINⅡ+ (all P<0.05). (3) When cytology was ≤low-grade squamous intraepithelial lesion (LSIL) and ≥ASC-H, the detection rate of CINⅡ+ in ECC CINⅠ was significantly higher than that of biopsy CINⅠ (all P<0.001). In ECC CINⅠ, the rate of CINⅡ+ with cytology ≤LSIL was significantly lower than that in cytology ≥ASC-H (56.0% vs 25.9%; χ2=49.38, P<0.001). In type Ⅰ/Ⅱ of TZ, the detection rate of CINⅡ+ between ECC CINⅠand biopsy CINⅠ had no significantly different; while in type Ⅲ of TZ, there was significantly different (72.7% vs 46.2%; χ2=4.02, P=0.045). In ECC CINⅠ, type Ⅲof TZ was significantly higher in the rate of CINⅡ+ than that of type Ⅰ/Ⅱ of TZ (72.7% vs 21.7%; χ2=16.38, P<0.001). When cytology ≥ASC-H, type Ⅲ of TZ and colposcopy impression of HSIL were combined, the rate of CINⅡ+ in ECC CINⅠ was 6/6 while 1/3 in biopsy CINⅠ. Conclusions: Cytology ≥ASC-H, ECC CINⅠ and type Ⅲ TZ are the risk factors of LEEP CINⅡ+. However, cytology ≥ASC-H is more valuable in predicting LEEP CINⅡ+ than ECC CINⅠ. For patients with ECC CINⅠ to perform LEEP, it is recommended that cytology ≥ASC-H is taken as the first level stratification, and type Ⅲ TZ is taken as the second level stratification. The colposcopy impression of patients is recommended for a reference parameter.

[Value of high-resolution anoscopy in the diagnosis of anal precancerous lesions].

Objective: To evaluate the value of high-resolution anoscopy (HRA) in the diagnosis of anal precancerous lesions. Methods: A retrospective cohort study was performed, which included 142 patients who underwent HRA in vulvar and anal clinic at Obstetrics and Gynecology Hospital of Fudan University from January 2014 to December 2019. With the perianal and anal canal biopsy pathology as the "gold standard", the diagnostic value of HRA and specific findings for anal precancerous lesions were evaluated and the clinical characteristics of patients with anal precancerous lesions were analyzed. Results: (1) Agreement between HRA and anal pathology were 76.6% (95/124, perianal) and 70.0% (84/120, anal canal), in which there was no significant difference (χ2=1.365, P=0.243). The strength of agreement with weighted Kappa statistic were 0.604 (perianal) and 0.455 (anal canal) respectively. HRA diagnosis were more overestimated [16.9% (21/124) in perianal and 25.0% (30/120) in anal canal] than underestimated [6.5% (8/124) in perianal and 5.0% (6/120) in anal canal]. The sensitivity and specificity of HRA in the diagnosis of anal precancerous lesions were all more than 60.0% (perianal lesions: 97.8% and 74.7%; anal canal lesions: 90.9% and 66.7%), and Youden's index were >0.5 (perianal lesions: 0.725; anal canal lesions: 0.576). The positive predictive value of HRA in anal canal lesions (50.8%) was lower than that in perianal lesions (68.8%). (2) The thin acetowhite epithelium was the most common finding in anal precancerous lesions, and its performance in anal canal lesions (the sensitivity, the specificity and the Youden's index were 78.8%, 62.4% and 0.412, respectively) were better than those in perianal lesions (the sensitivity, the specificity and the Youden's index were 28.9%, 96.9% and 0.258, respectively). The dense acetowhite epithelium and vascular patterns were only seen in anal canal lesions. Lugol's iodine was little useful for perianal lesions (the incidence of iodine negative was 0),but quite useful to evaluate the canal lesions (the positive predictive value was 83.3% and the negative predictive value was 82.3%). (3) The average age of patients with low-grade anal precancerous lesion was (37±10) years old, and high-grade anal precancerous lesion was (42±11) years old, and there was significant difference between them (P=0.034). Age curve showed that the peak age was 30-40 years old. Vulvar intraepithelial lesion was the risk factor of anal precancerous lesions (χ2=4.284, P<0.05). Conclusions: HRA patterns are reliable in the diagnosis of anal precancerous lesions, which is important for guiding biopsy. However, it is easy to be overestimated, especially for anal canal lesions. The acetowhite epithelium is the most common finding in anal precancerous lesions, but vascular patterns are only seen in anal canal lesions.

Tri-domain proteins 27 reduce inflammation and apoptosis in HK-2 cells and protect against acute kidney injury in mice.

OBJECTIVE: The kidney is one of the most commonly damaged organs in sepsis. Acute kidney injury (AKI) induced by sepsis is a clinically dangerous disease with a high mortality rate. Therefore, it is particularly important to find a way to prevent and treat sepsis-induced AKI. MATERIALS AND METHODS: Human renal tubular epithelial cell line (HK-2) and 8-week-old C57BL/6 mice were used. Lipopolysaccharide (LPS) was used to induce HK-2 cell injury and mouse AKI. Lentiviruses overexpressing TRIM27 were constructed to increase TRIM27 expression in HK-2 cells. Then, the effects of TRIM27 on the inflammation and apoptosis of HK-2 cells were analyzed, and those of TRIM27 recombinant protein on AKI in mice was detected by immunohistochemical staining and Western blot. RESULTS: It was found that TRIM27 overexpression reduced the expressions of inflammatory factors and signaling molecules in apoptosis-related pathways in HK-2 cells, but increased the ratio of Bcl-2 to Bax in HK-2 cells, indicating the anti-apoptotic effect of TRIM27. Toll-like receptor 4 (TLR4)/NF-κB signaling pathway is an important mechanism of LPS mediated renal injury, and TRIM27 overexpression in HK-2 cells significantly inhibited the activity of TLR4/NF-κB signaling pathway. In addition, AKI was significantly relieved in mice treated with TRIM27 recombinant. CONCLUSIONS: TRIM27 exerts anti-inflammatory and anti-apoptotic effects by inhibiting the TLR4/NF-κB signaling pathway, which effectively alleviates LPS-induced HK-2 cell damage and mouse AKI.

Circular RNA circ-ABCB10 promotes the proliferation and invasion of thyroid cancer by targeting KLF6.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA circ-ABCB10 promotes the proliferation and invasion of thyroid cancer by targeting KLF6, by X.-T. Han, J.-Q. Jiang, M.-Z. Li, Q.-M. Cong, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1271-1277-DOI: 10.26355/eurrev_202002_20182-PMID: 32096158" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20182.

Circular RNA circ-ABCB10 promotes the proliferation and invasion of thyroid cancer by targeting KLF6.

OBJECTIVE: Recent researches have proved that circular RNAs (circRNAs) play important roles in many diseases. Thyroid cancer is one of the most common malignant tumors worldwide. Therefore, the aim of this study was to investigate the role of circ-ABCB10 in thyroid cancer. PATIENTS AND METHODS: Circ-ABCB10 expression in 40 paired thyroid cancer tissues and adjacent normal tissues was monitored by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Subsequently, circ-ABCB10 was silenced or overexpressed in thyroid cancer cells. Function assays were conducted to explore the role of circ-ABCB10 in the proliferation and invasion of thyroid cancer in vitro. Furthermore, RT-qPCR and Western blot assay were performed to elucidate the potential underlying mechanism. RESULTS: Circ-ABCB10 expression was significantly higher in thyroid cancer tissues than that in adjacent tissues. The growth ability of thyroid cancer cells was significantly inhibited after circ-ABCB10 silence. However, the growth ability of thyroid cancer cells was remarkably promoted after circ-ABCB10 was overexpressed in vitro. Similarly, the invasion of thyroid cancer cells was significantly inhibited or promoted after circ-ABCB10 silence or overexpression, respectively. Besides, the expression of KLF6 was markedly up-regulated by the silence of circ-ABCB10. However, KLF6 expression was down-regulated by overexpression of circ-ABCB10. CONCLUSIONS: Circ-ABCB10 was first identified as a novel oncogene in thyroid cancer. Furthermore, it significantly enhanced the proliferation and invasion of thyroid cancer by targeting KLF6. Our findings suggested that circ-ABCB10 could be used as a potential therapeutic target in thyroid cancer.

Evaluation of Potato virus X mild mutants for cross protection against severe infection in China.

BACKGROUND: Cross protection is a promising alternative to control plant viral diseases. One critical factor limiting the application of cross protection is the availability of attenuated mutants or mild strains. Potato virus X (PVX) infects many crops and induces huge economic losses to agricultural production. However, researches on the variability and mechanism of PVX virulence are scarce. METHODS: The mutants were obtained by introducing mutations into the RNA dependent RNA polymerase (RdRp) gene of PVX via site-directed mutagenesis. Attenuated mutants were screen according to their symptoms in Nicotiana benthamiana plants. The protection efficacy against severe infection were evaluated with interval of 5, 10 and 15 days. RESULTS: Among the 40 mutants obtained, four mutants carrying substitutions of either Glu46, Asn863, Asn968 or Glu1001 to Ala in PVX RdRp showed drastically attenuated symptom, accompanying with reduced accumulation levels of coat protein, plus- and minus-sense RNAs. When the interval between protective and challenging inoculations was 15 days, mutant E1001A (with substitution of Glu1001 to Ala in RdRp) provided complete protection against severe infection in both Nicotiana benthamiana and tomato, while E46A (Glu46 mutated to Ala) provided incomplete protection. To reduce the risk of reverse mutation, we constructed mutant dM which carries double mutations of both Glu46 and Glu1001 to Ala in RdRp. The mutant dM could provide effective protection against severe PVX infection. CONCLUSION: Mutations of Glu46, Asn863, Asn968 or Glu1001 to Ala in PVX RdRp significantly reduced the viral symptoms. Mutants E1001A and E46A could provide effective protection against wild type PVX in both Nicotiana benthamiana and tomato. These results provide theoretical and practical bases for the control of PVX via cross protection.

[Detection trend of vaginal intraepithelial neoplasia diagnosed by colposcopy guided biopsy from 2013 to 2015].

Objective: To explore the detection trend of vaginal intraepithelial neoplasia (VaIN) of lower genital tract from 2013 to 2015. Methods: A retrospective analysis was undertaken of colposcopy-directed biopsy of cervical, vaginal and vulvar intraepithelial neoplasia lesions include cervical intraepithelial neoplasia (CIN), VaIN and vulvar intraepithelial neoplasia (VIN) in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to December 2015. Results: (1) Overall data of CIN, VaIN and VIN: a total of 16 732 cases were diagnosed of lower genital intraepithelial neoplasia in 3 years, accounting for 23.20% (16 732/72 128) of total colposcopy-directed biopsy cases. Among them, CIN, VaIN and VIN accounted for 19.48% (14 053/72 128), 2.67% (1 923/72 128), 1.05% (756/72 128) of total colposcopy-directed biopsy cases of the lower genital tract, 83.99% (14 053/16 732), 11.49% (1 923/16 732), 4.52% (756/16 732) of total lower genital intraepithelial neoplasia, respectively. (2) Annual data of CIN, VaIN and VIN from 2013 to 2015. The annual proportion of CIN in all intraepithelial neoplasia of lower gential tract was basically stable, consisting of 86.02%(3 955/4 598),83.25%(4 795/5 760) and 83.20% (5 303/6 374), respectively. The annual proportion of VaIN was gradually increasing, consisting of 8.09%(372/4 598), 12.45%(717/5 760) and 13.08%(834/6 374), respectively. The annual proportion of VIN was gradually decreasing, consisting of 5.89%(271/4 598), 4.31%(248/5 760) and 3.72%(237/6 374), respectively. Conclusion: The increasing detection of VaIN from 2013 to 2015 might correlate with the increasing attention to inspection of the entire vaginal wall.

RN1, a novel galectin-3 inhibitor, inhibits pancreatic cancer cell growth in vitro and in vivo via blocking galectin-3 associated signaling pathways.

Galectin-3 (Gal-3) has been implicated in pancreatic ductal adenocarcinoma (PDAC), and its candidacy as a therapeutic target has been evaluated. Gal-3 is widely upregulated in tumors, and its expression is associated with the development and malignancy of PDAC. In the present study, we demonstrate that a polysaccharide, RN1, purified from the flower of Panax notoginseng binds to Gal-3 and suppresses its expression. In addition, RN1 markedly inhibits PDAC cells growth in vitro, in vivo and in patient-derived xenografts. Mechanistically, RN1 binds to epidermal growth factor receptor (EGFR) and Gal-3, thereby disrupting the interaction between Gal-3 and EGFR and downregulating extracellular-related kinase (ERK) phosphorylation and the transcription factor of Gal-3, Runx1 expression. Inhibiting the expression of Runx1 by RN1, suppresses Gal-3 expression and inactivates Gal-3-associated signaling pathways, including the EGFR/ERK/Runx1, BMP/smad/Id-3 and integrin/FAK/JNK signaling pathways. In addition, RN1 can also bind to bone morphogenetic protein receptors (BMPR1A and BMPR2) and block the interaction between Gal-3 and the BMPRs. Thus, our results suggest that a novel Gal-3 inhibitor RN1 may be a potential candidate for human PDAC treatment via multiple targets and multiple signaling pathways.

The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network.

The LIM protein AJUBA is a scaffold protein participating in the regulation of cell adhesion, mitosis, DNA damage, cell differentiation, proliferation, migration and gene transcription. However, its roles in tumorigenesis and progression are poorly defined. Here, we report that AJUBA is highly expressed in colorectal cancer (CRC) and promotes CRC cell growth in culture and in xenografted mice via an inhibition of apoptosis. AJUBA represses the expression of IFIT2 gene, an interferon-stimulated gene and a known apoptosis inducer and tumour suppressor to mediate its resistance to apoptosis. Mechanistic investigations reveal that AJUBA specifically binds the FERM domain of JAK1 to dissociate JAK1 from the IFNγ recepter, resulting in an inhibition of STAT1 phosporylation and concomitantly its nuclear translocation. Clinically, the level of AJUBA in CRC specimens is negatively correlated with the levels of IFIT2 and pSTAT1. Collectively, these studies demonstrate that AJUBA can promote CRC growth via inhibiting apoptosis and serve as a target for the therapeutics and a marker for diagnosis of CRC.

Pilot study special AT-rich sequence-binding protein 1 investigating as a potential biomarker for esophageal squamous cell carcinoma.

In the present study, we aimed to evaluate the expression of special AT-rich sequence-binding protein 1 (SATB1) in esophageal squamous cell carcinoma (ESCC) and assess the correlation between its expression and the clinicopathological features and prognosis of the disease. SATB1 expression in ESCC tissue was determined by using immunohistochemical analysis, quantitative real-time polymerase chain reaction, and western blot analysis. The relationship between SATB1 expression and clinicopathological features was examined by using the chi-squared test, and the survival rate was calculated by using the Kaplan-Meier survival curve. The correlation between the indicators and patient survival was estimated by using a Cox regression analysis. High SATB1 expression in was detected in 48.3% and 7.8% of ESCC and normal esophagus tissues (P < 0.05), respectively. SATB1 expression did not significantly correlate with clinicopathological features. The Kaplan-Meier curve indicated that patients with high SATB1 expression had significantly shorter survival than those with low SATB1 expression. In a multivariate Cox regression model, high SATB1 expression was identified as an independent prognostic factor for patients with ESCC. In conclusion, these results suggest that high SATB1 expression is predictive of poor prognosis in ESCC and may be a promising new candidate for targeted therapies for ESCC.

p57Kip2 is an unrecognized DNA damage response effector molecule that functions in tumor suppression and chemoresistance.

The DNA damage response (DDR) helps to maintain genome integrity, suppress tumorigenesis and mediate the radiotherapeutic and chemotherapeutic effects on cancer. Here we report that p57Kip2, a cyclin-dependent kinase (CDK) inhibitor implicated in the development of tumor-prone Beckwith-Wiedemann syndrome, is an effector molecule of the DNA-damage response. Genotoxic stress induces p57Kip2 expression via the bone morphogenetic protein-Smad1 and Atm-p38MAPK-Atf2 pathways in p53-proficient or -deficient cells and requires the Smad1-Atf2 complex that facilitates their recruitment to the p57Kip2 promoter. Elevated p57Kip2 induces G1/S phase cell cycle arrest but inhibits cell death in response to DNA damage and acts in parallel with p53 to suppress cell transformation and tumor formation. p57Kip2 is also upregulated in stage I and II clinical rectal tumor samples, likely due to genome instability of precancerous and/or early cancer cells. Targeting p57Kip2 in primary rectal cancer cells and tumor models resulted in increased sensitivity to doxorubicin, suggesting that p57Kip2 has a role in chemoresistance, which is consistent with its pro-survival function. These findings place p57Kip2 in DDR and uncover molecular mechanisms by which p57Kip2 suppresses tumorigenesis and causes chemoresistance.

Incidence and predictors of surgical-site infections in Vietnam.

OBJECTIVE: To determine the incidence of, and risk factors for, surgical-site infections (SSIs). DESIGN: Prospective observational study of all patients undergoing surgery during a 3-month period. SETTING: Two urban hospitals in Hanoi, Vietnam. PATIENTS: All 697 patients admitted for emergent and elective surgery. METHODS: Data were collected on all patients undergoing surgery during a 3-month period at each hospital. We stratified the data by type of surgery, wound class, and Study on the Efficacy of Nosocomial Infection Control (SENIC) risk index. The analysis was done with the data sets from each hospital separately and with the combined data. The risk factors for SSI were identified using a logistic-regression model. RESULTS: During the period of observation, 10.9% of 697 patients had SSI. The SSI rate was 8.3% for clean wounds, 8.6% for clean-contaminated, 12.2% for contaminated, and 43.9% for dirty wounds. The lowest rate of SSI (2.4%) was found in obstetric-gynecologic procedures and the highest rate (33.3%) in cardiothoracic operations. Using the SENIC risk index, the incidence of SSI in low-risk patients was 5.1%; for medium-risk patients, 13.5%, and high-risk patients, 24.2%. In a logistic-regression model, abdominal surgery (odds ratio [OR], 4.46; P<.01) and wound class IV (OR, 5.67; P<.01) were significant predictors of SSI. All patients were treated with prolonged courses of perioperative antibiotics. Overall infection control practices were poor as a result of deficient facilities, limited surgical instruments, and a lack of proper supplies for wound care and personal hygiene. CONCLUSIONS: There was a higher incidence of SSI in low-risk patients in Vietnam compared with developed countries. Excessive reliance on antimicrobial therapy as a means to limit SSI places patients at higher risk of adverse effects from treatment and also may contribute to worsening problems with antimicrobial resistance. Establishment of an infection control program with guidelines for antimicrobial use should improve the use of prophylactic antibiotics and attention to proper surgical and wound-care techniques. These interventions also should reduce the incidence of SSI and its associated morbidity and costs.

Phase separation with multiple length scales in polymer mixtures induced by autocatalytic reactions.

A ternary polymer blend with two components photo-cross-linked independently in its miscible region undergoes phase separation, exhibiting morphology with multiple length scales. Contrary to the case of thermally induced phase separation, the morphology exhibits a unimodal-->multimodal transition. It is shown that these multiple length scales are caused by the inhomogeneous freezing kinetics of the cross-linking process. This inhomogeneity arises from the autocatalytic feedback driven by the couplings between concentration fluctuations and the photo-cross-linking reactions.

[Can esophagogastric anastomosis prevent gastroesophageal reflux].

OBJECTIVE: To investigate the possible anti-reflux function of esophagogastric anastomosis in the patients after receiving resection of cardiac cancer. METHODS: One hundred and ninety-two patients were studied by video-assisted gastroscopy, manometry, 24-h pH esophageal monitoring, radioscintigraphy and scanning electron microscopy. RESULTS: Abnormalities were found in 90.2% of patients through endoscopy. Resting pressure in esophageal body was higher than that in normal controls, and in the stomach, lower. Twenty-four hour pH monitoring demonstrated that gastroesophageal reflux (GER) did not occur when the patients slept in semi-reclining position, and occurred in all patients when slept in supine position. Scintigraphic study showed that 2/3 of the patients had reflux, occurrence of which was not affected by the length of postoperative period. Scanning electron microscopic examination showed that degeneration, exfoliation of esophageal mucosal epithelial cell, and derangement of micro-fold and inflammatory oedema of cytomembrane may be directly caused by reflux. CONCLUSIONS: GER exists in the majority of the patients after esophagogastrectomy and esophagogastrostomy for cardiac cancer. The occurrence of GER is not affected by the length of postoperative period. Some detecting methods fail to show the existence of GER, and 24-h pH monitoring is the most reliable method for detecting GER. Sleep in semireclining position is an effective method of preventing GER in postoperative patients.

[Lugol's solution in endoscopic diagnosis of early esophageal cancer].

About 1500 high-risk subjects of esophageal cancer were found during screening by balloon cytology and all of them were examined endoscopically. Among them, 120 were considered as having early esophageal cancer and precancerous lesions. During the examination, Lugol's solution staining was used and guiding biopsy was taken. 98 subjects with unstained lesions were found, and biopsy showed early esophageal cancer in 60 (61.2%) and moderate and severe dysplasia in 38 (38.8%). It is usually extremely difficult to detect and localize the very early esophageal mucosal and submucosal carcinoma. But endoscopic examination and using Lugol's solution staining with multiple spots biopsy from unstained area are of great assistance. Minute malignant lesions may not be overlooked.

Fluorescent-labeled oligonucleotide probes: detection of hybrid formation in solution by fluorescence polarization spectroscopy.

Fluorescein-labeled oligonucleotides as DNA-probes were synthesized and used to monitor hybrid formation, namely to detect DNA or oligonucleotide sequence in solution. The introduction of fluorescein to oligonucleotides was carried out by oxidation of a hydrogen phosphonate linkage with ethylenediamine or hexamethylenediamine as a tether and by a subsequent labeling of the primary amine moiety by FITC. Fluorescence anisotropy, r, was adopted as an index to monitor the behavior of F-probe in solution. An increase in the anisotropy was observed upon an increase in the chain-length of F-probe. When F-Probe formed a hybrid with its complementary oligonucleotide in solution, the r value increased compared to that of F-Probe itself. These observations clearly indicate that measurements of r in solution will readily lead to the monitoring of the presence of a hybrid in solution. Consequently, it is promising to detect a certain nucleic acid sequence in solution using fluorescent-labeled oligonucleotides.