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Da Ma, Zhi-Guang Yao, Yan-Ping Guo, Rui-Fa Wu Department of Pediatric General Surgery, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, 523000, People’s Republic of ChinaCorrespondence: Da MaDepartment of Pediatric General Surgery, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of ChinaTel/Fax +86 769-86186253Email mada66_doc@163.comObjective: Cryptorchidism is the most common congenital disability and is defined as the absence of one or both testicles in the scrotum during fetal development. In patients with cryptorchidism, lowered serum inhibin B levels suggest testicular dysfunction. The practical application of serum inhibin B levels in childhood remains controversial. The purpose of this study was to observe the post-operational changes of serum inhibin B levels in patients with cryptorchidism and provide evidence that serum inhibin B is a potential marker for the efficacy of testicular surgery.Methods: A total of 83 male children with cryptorchidism were enrolled in this study. All the children had blood samples taken by venipuncture on the day of surgery. The serum inhibin B levels in the blood samples were measured using an ELISA kit. Paired t-tests were used to assess differences between the groups.Results: The results show that, compared with the preoperative values, there was a statistically significant increase in serum inhibin B values one month after the operation in each group (P < 0.05). Compared with the one-month post-operation results, there were no significant changes six months after operation in each group (P> 0.05). However, serum inhibin B values decreased significantly in all groups at 12 months post-operation (P < 0.05), suggesting that serum inhibin B values are significantly correlated with age. Correlation analysis showed that serum inhibin B was negatively correlated with age from 6 to 36 months, and the correlation coefficient was − 0.488.Conclusion: Serum inhibin B can be used as a short-term evaluation index of cryptorchidism surgery rather than as a long-term indicator.Keywords: serum inhibin B, children, cryptorchidism surgery

Asthma is a prevalent chronic inflammatory airway disease that affects both adults and children. Inflammation-induced airway remodeling can lead to irreversible damage to the airways. Traditional Chinese medicine (TCM) plays a significant role in healthcare, offering potential improvements for chronic airway inflammation associated with asthma. The objective of this study is to investigate the efficacy of Pingchuan formula (PCF) in treating asthma and explore its underlying mechanisms. The asthmatic model mice were sensitized on days 1 and 7, followed by aerosolized OVA challenge for a total of 21 times starting from day 14, spanning weeks 3 to 9. PCF was administered daily after the first challenge. The mice were orally dosed daily based on their individual body weights for a continuous period of 47 days. The examined items encompassed proteomic analysis of the target proteins impacted by PCF. The levels of interleukins IL-1β, IL-18, and transforming growth factor-β (TGF-β) in bronchoalveolar lavage fluid (BALF) were measured using ELISA. Immunohistochemistry was employed to assess the expression levels of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), caspase-1, and TGF-β in the airways. Western blotting and real-time quantitative PCR analysis were conducted to determine NLRP3 and caspase-1 expression levels. Additionally, Western blotting was performed to evaluate C-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), matrix metalloproteinase-9 (MMP-9), N-cadherin, E-cadherin, and tenascin C (T-NC) expression. Compared to the asthma model group, histological analysis using hematoxylin and eosin (HE) staining and Masson staining revealed that PCF exhibited a significant reduction in airway inflammation exudation and collagen fiber production in asthmatic mice. The proteomics analysis revealed that there were 174 proteins exhibiting differential expression in the PCF group compared to the asthma model group, indicating a strong association with negative regulation of the cell cycle and inflammation in the airways of asthmatic individuals. The PCF also exhibited a significant reduction in the protein and mRNA expressions of NLRP3 and caspase-1 in lung tissue (P<0.05). Additionally, it decreased the protein expressions of ASC, p-JNK, MMP-9, E-cadherin, and T-NC while increasing N-cadherin levels (P<0.05). The inflammatory factors IL-1β, IL-18 and TGF-β were reduced (P<0.05). This study revealed that Pingchuan Decoction can inhibit airway remodeling by inhibiting NLRP/IL-1β and JNK pathway activation, and effectively improve airway histological inflammation and remodeling in mice.

Objective: The objective of this study was to examine the utility of a combination of the modified Caprini score and D-dimer levels for the evaluation and management of lower extremity venous thrombosis following lung cancer surgery. The purpose was to offer insights for developing clinical intervention programs., Methods: The study sample consisted of 224 patients who underwent surgery for lung cancer at the First Central Hospital of Baoding City. General patient data and D-dimer levels on the first day post-surgery were collected. The modified Caprini risk assessment score was calculated. All patients underwent ultrasonography of the lower limb veins before and after surgery to identify venous thrombosis in the lower limb veins. Differences in lower extremity venous thrombosis and D-dimer levels among patients in various modified Caprini score groups were compared and analyzed., Results: Based on the modified Caprini risk assessment score, all patients were categorized into three groups: the low-risk, medium-risk, and high-risk groups. The groups did not differ significantly in terms of age, but the differences in the rates of lower extremity venous thrombosis in the low, intermediate, and high-risk Caprini risk groups (16.5%, 19.2%, and 37.1%, respectively) were statistically significant. Out of the total 224 patients, 47 (21%) were diagnosed with venous thromboembolisms post-surgery, and all of them had thrombosis of the intermuscular veins of the lower extremity. The difference in the modified Caprini risk assessment score between patients with and without lower extremity venous thrombosis was statistically significant (P = 0.035), as were the postoperative D-dimer levels (1.28 ± 1.64 vs. 2.69 ± 2.77, respectively; P < 0.05) between these two groups of patients. The modified Caprini risk assessment score showed an association with lower extremity venous thrombosis (r = 0.15, P = 0.56) with an area under the receiver operating characteristic curve (AUC) of 0.59., Conclusion: In this study, we found that combining the modified Caprini risk assessment score with D-dimer measurements enhanced the accuracy of assessing the severity of deep vein thrombosis (DVT). This combination can be beneficial in evaluating thrombosis risk post-lung cancer surgery and holds significant clinical utility., (© 2024. The Author(s).)

Anthropogenic shifts in seas are reshaping fishing trends, with significant implications for aquatic food sources throughout this century. Examining a 21-year abundance dataset of Argentine shortfin squids Illex argentinus paired with a regional oceanic analysis, we noted strong correlations between squid annual abundance and sea surface temperature (SST) in January and February and eddy kinetic energy (EKE) from March to May in the Southwest Atlantic. A deeper analysis revealed combined ocean-atmosphere interactions, pinpointed as the primary mode in a rotated empirical orthogonal function analysis of SST. This pattern produced colder SST and amplified EKE in the surrounding seas, factors crucial for the unique life stages of squids. Future projections from the CMIP6 archive indicated that this ocean-atmosphere pattern, referred to as the Atlantic symmetric pattern, would persist in its cold SST phase, promoting increased squid abundance. However, rising SSTs due to global warming might counteract the abundance gains. Our findings uncover a previously unrecognized link between squids and specific environmental conditions governed by broader ocean-atmosphere interactions in the Southwest Atlantic. Integrating these insights with seasonal and decadal projections can offer invaluable information to stakeholders in squid fisheries and marine conservation under a changing climate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Psoriasis is a chronic skin disease characterized by unique scaling plaques. However, during the acute phase, psoriatic lesions exhibit eczematous changes, making them difficult to distinguish from atopic dermatitis, which poses challenges for the selection of biological agents. This study aimed to identify potential diagnostic genes in psoriatic lesions and investigate their clinical significance., Methods: GSE182740 datasets from the GEO database were analyzed for differential analysis; machine learning algorithms (SVM-RFE and LASSO regression models) are used to screen for diagnostic markers; CIBERSORTx is used to determine the dynamic changes of 22 different immune cell components in normal skin lesions, psoriatic non-lesional skin, and psoriatic lesional skin, as well as the expression of the diagnostic genes in 10 major immune cells, and real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry are used to validate results., Results: We obtained 580 differentially expressed genes (DEGs) in the skin lesion and non-lesion of psoriasis patients, 813 DEGs in mixed patients between non-lesions and lesions, and 96 DEGs in the skin lesion and non-lesion of atopic dermatitis, respectively. Then 144 specific DEGs in psoriasis via a Veen diagram were identified. Ultimately, UGGT1, CCNE1, MMP9 and ARHGEF28 are identified for potential diagnostic genes from these 144 specific DEGs. The value of the selected diagnostic genes was verified by receiver operating characteristic (ROC) curves with expanded samples. The the area under the ROC curve (AUC) exceeded 0.7 for the four diagnosis genes. RT-qPCR results showed that compared to normal human epidermis, the expression of UGGT1, CCNE1, and MMP9 was significantly increased in patients with psoriasis, while ARHGEF28 expression was significantly decreased. Notably, the results of CIBERSORTx showed that CCNE1 was highly expressed in CD4+ T cells and neutrophils, ARHGEF28 was also expressed in mast cells. Additionally, CCNE1 was strongly correlated with IL-17/CXCL8/9/10 and CCL20. Immunohistochemical results showed increased nuclear expression of CCNE1 in psoriatic epidermal cells relative to normal., Conclusion: Based on the performance of the four genes in ROC curves and their expression in immune cells from patients with psoriasis, we suggest that CCNE1 possess higher diagnostic value., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Zhou, Luo and Wu.)

Human activity and climate change affect biodiversity and cause species range shifts, contractions, and expansions. Globally, human activities and climate change have emerged as persistent threats to biodiversity, leading to approximately 68% of the ~522 primate species being threatened with extinction. Here, we used habitat suitability models and integrated data on human population density, gross domestic product (GDP), road construction, the normalized difference vegetation index (NDVI), the location of protected areas (PAs), and climate change to predict potential changes in the distributional range and richness of 26 China's primate species. Our results indicate that both PAs and NDVI have a positive impact on primate distributions. With increasing anthropogenic pressure, species' ranges were restricted to areas of high vegetation cover and in PAs surrounded by buffer zones of 2.7-4.5 km and a core area of PAs at least 0.1-0.5 km from the closest edge of the PA. Areas with a GDP below the Chinese national average of 100,000 yuan were found to be ecologically vulnerable, and this had a negative impact on primate distributions. Changes in temperature and precipitation were also significant contributors to a reduction in the range of primate species. Under the expected influence of climate change over the next 30-50 years, we found that highly suitable habitat for primates will continue to decrease and species will be restricted to smaller and more peripheral parts of their current range. Areas of high primate diversity are expected to lose from 3 to 7 species. We recommend that immediate action be taken, including expanding China's National Park Program, the Ecological Conservation Redline Program, and the Natural Forest Protection Program, along with a stronger national policy promoting alternative/sustainable livelihoods for people in the local communities adjacent to primate ranges, to offset the detrimental effects of anthropogenic activities and climate change on primate survivorship., (© 2023 John Wiley & Sons Ltd.)

To resolve the issue of scientific planning and rational layout of different vegetable greenhouses in Inner Mongolia Autonomous Region, we selected the days of low temperature in winter, sunshine hours, overcast days, extreme minimum temperature, days of monsoon disaster, days of snow cover in production season of greenhouse as the climate zoning indicators, based on ground-based observation data from 119 meteorological stations (1991 to 2020) and the growing demand of leafy and fruity vegetables in greenhouse, combined with the analysis of key meteorological factors in production season and the study of meteorological disaster indicators such as low temperature and cold damage, wind disaster, snow disaster. We analyzed the indices, classification and division of comprehensive climate suitability zoning of leafy and fruity vegetables at various slopes (35°, 40°) of solar greenhouse by the weighted sum method. The results showed that the climatic suitability zoning grades of leafy and fruity vegetables at 35° and 40° slope of greenhouse was highly consistent, and that the greenhouse climate suitability of leafy vegetables was higher than that of fruity vegetables in the same region. As the slope increased, wind disaster index decreased and snow disaster index increased. Climate suitability was different in areas affected by wind and snow disasters. The northeast of the study area was mainly affected by snow disasters, and the climate suitability of 40° slope was higher than 35°. The southeast of the study area was mainly affected by wind disasters, and the climate suitability of 35° slope was higher than 40°. Alxa League, Hetao Irrigation District, Tumochuan Plain, most parts of Ordos, southeast of Yanshan foothills and the south of West Liaohe Plain were the most suitable area for the solar greenhouse, because they had the suitable solar and hot resources and the low risks of wind and snow damage, which were also the key development areas of current and future facility agriculture. Due to the deficiency of solar and hot resources, high energy consumption in greenhouse production and frequent snow storms, the area around Khingan range in the northeast of Inner Mongolia was unsuitable for greenhouse.

A cold collision between atoms and molecules (<1 K) is one of the hot research fields in atomic and molecular physics. At low temperatures, the number of partial waves participating in the collision process decreases dramatically, and quantum phenomena start to emerge. The reaction is often dominated by quantum tunneling, and pronounced resonances can exist on collision cross sections. Here, we report on an apparatus designed for studying cold collisions between metastable noble gas atoms and alkali atoms. Our apparatus features a combined Magneto-Optical-Trap (MOT) and velocity map imaging (VMI) system. The center of a Rb MOT is overlapped with the VMI system. Cold Kr* atoms are launched toward the Rb atoms to induce Kr* + Rb reactions. The collision energy between the two species can be varied from 100 mK to 20 K. With this setup, we are planning to explore the quantum phenomena in Kr* + Rb cold collisions, including the shape resonance and stereodynamics in the reaction., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Competing Interests: The author declares no conflict of interest.

Chinese Jiang-flavor Baijiu is the most widely consumed liquor. Jiang-flavor Daqu, a fermentation starter, is important sources of key flavors of Jiang-flavor Baijiu. Some microbes play significant roles in flavor formation of Daqu. In order to clarify the microbial population that promotes the formation of Daqu flavor, we use high throughput sequencing technology combined with headspace solid-phase microextraction gas chromatography-mass spectrometry to investigate microbial population and volatile compounds in Jiang-flavor Daqu. In addition, the dynamic changes of physicochemical factors and enzyme activities in Jiang-flavor Daqu were investigated. Correlations between microbial population, volatile compounds, physicochemical factors, and enzyme activities of Jiang-flavor Daqu were disclosed by redundancy analysis and Spearman correlation analysis. A total of 66 volatile compounds were identified and 14 primary microorganisms were selected. Results showed that high temperature environment could promote the formation of acids, aldehydes and ketones, phenols, furans by affecting the growth of Monascus, Trichomonascus, Cutaneotrichosporon, Wallemia, Millerozyma, Nigrospora, Cladosporium, Bacillus, and Pediococcus in the early fermentation stage. While high nitrogen environment was more suitable for the growth of Virgibacillus and Kroppenstedtia, who could promote the formation of pyrazines in the late fermentation stage. PRACTICAL APPLICATIONS: This study has provided a scientific basis for the directed regulation of Daqu fermentation through physicochemical factors, developed scientific basis for artificially constructing Daqu microbial population and obtaining an easy-to-operate, reproducible fermentation system for Daqu production., (© 2022 Wiley Periodicals LLC.)

Phytochemical investigation on the 95% alcohol extract of the aerial part of Inula japonica led to the isolation of three new compounds, inulanolides F-G ( 1-2 ) and 17 α -carboxaldehyde-ent-kaur-18-oic acid ( 3 ), together with four known compounds ( 4-7 ). The structures of new compounds were elucidated by using spectroscopic data. Most of the isolated compounds showed significant anti-inflammatory activities.

Hydrogen sulfide and biothiol molecules such as Cys and GSH acted important roles in many physiological processes. To simultaneously detect and distinguish them was quite necessary by a suitable fluorescent probe. A novel chemosensor 4-(4-(benzo[d]thiazol-2-yl)-2-methoxyphenoxy)-7-nitrobenzo[c][1,2,5]oxadiazole (BMNO) was designed to detect H 2 S/Cys/GSH using the combination of nitrobenzofurazan (NBD) and benzothiazole fluorophores linked by a facile ether bond. The probe BMNO was developed for simultaneous identification of H 2 S, Cys and GSH. Noticeably, the color changes (from colorless to light purple, light orange and light yellow) of probe BMNO solutions for sensing H 2 S, Cys and GSH could be observed by naked eyes, respectively. The probe BMNO exhibited high selectivity and sensitivity for H 2 S, Cys and GSH showing distinct optical signal with detection limit as low as 0.15 μM, 0.03 μM and 0.14 μM, respectively. The sensing mechanism was clarified by spectrum analysis and some controlled experiments. In addition, these outstanding properties of probe BMNO enabled its practical applications in detection H 2 S in beer, and in cell imaging for Cys and GSH as well., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures., Competing Interests: None

A phytochemical study performed on Inula japonica led to isolation of a new 1,10-seco-sesquiterpene dimer Neolinulicin A (1) and 1,10-seco-sesquiterpene Neolinulicin B (2), together with nine known sesquiterpenes (3-11). Among them, Neolinulicin A (1), which has a new carbon skeleton, was a Diels-Alder [4 + 2] adduct of two sesquiterpene moieties. Their structures were established by extensive spectroscopic analysis. All of the isolated compounds showed inhibition of NO production in RAW 264.7 macrophages. The findings might supply information for the future design of anti-inflammatory agents from I. japonica., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of high-risk HPV (HR-HPV) genotyping with vaginal self-sampling in primary screening and combining cytology or viral load for HR-HPV positive as secondary screening strategies. Methods: The data referring to HR-HPV genotyping of self-collected sample with mass array matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), HR-HPV viral load of physician-collected sample with hybrid capture Ⅱ (HC-Ⅱ), liquid-based cytology and histology of 8 556 women were from Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST-Ⅱ) conducted between April 2009 and April 2010. The data were reanalyzed to determine the sensitivity and specificity to cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN Ⅱ + ), CIN of grade 3 or worse (CIN Ⅲ + ) when HR-HPV genotyping combining with colposcopy as primary screening strategy based on varied HR-HPV subtype (strategy 1, including 5 sub-strategies: 1a: HPV 16/18 positive; 1b: HPV 16/18/58 positive; 1c: HPV 16/18/58/31/33 positive; 1d: HPV 16/18/58/31/33/52 positive; 1e: any HR-HPV positive). The data were also compared to determine the efficacy of cytology (strategy 2, including 5 sub-strategies: 2a, 2b, 2c, 2d, 2e) or HR-HPV viral load (strategy 3, including 4 sub-strategies: 3a, 3b, 3c, 3d) of physician-collected sample as a triage with HR-HPV genotyping for self-sampling HR-HPV positives. Results: (1) The HR-HPV positive rate was 13.77% (1 178/8 556) in the self-collected samples of 8 556 pregnant women. Of them,the prevalences of HPV 16/18, HPV 16/18/58, HPV 16/18/58/31/33 and HPV 16/18/58/31/33/52 were 3.16% (270/8 556), 5.14% (440/8 556), 6.66% (570/8 556) and 9.81% (839/8 556), respectively. The HR-HPV viral load ≥10 relative light units/control (RLU/CO) was 8.87%(759/ 8 556), while cytological results ≥atypical squamous cell of undetermined signification (ASCUS) were 12.05% (1 031/8 556). (2) The strategy 1e had the highest sensitivities for CIN Ⅱ + , CIN Ⅲ + which were 92.70% and 94.33%,respectively,among 14 sub-strategies,while the lowest specificity and positive predictive value (PPV). Meanwhile,the required colposcopy referral rates were much higher than other 13 sub-strategies (13.77%). The other 4 sub-strategies of strategy 1 (1a, 1b, 1c, 1d), strategy 1a had the highest specificities for CIN Ⅱ + and CIN Ⅲ + (97.92%, 97.69%, respectively), while 1d had the highest sensitivities for CIN Ⅱ + and CIN Ⅲ + (88.41%, 92.20%, respectively). (3) Both strategies of referring self-sampling HPV 16/18 positives for immediate colposcopy followed by triage physician-collected sample cytology (≥ASCUS) or viral load (≥10 RLU/CO) for non-HPV 16/18 positives had significantly higher sensitivity and specificity for CIN Ⅱ, CIN Ⅲ + , as well as lower referral rates (strategy 2a and 3a). Additionally, based on these two secondary screening strategies, cumulatively using the other four HR-HPV (HPV 58, 31, 33 and 52) positives as triage for immediate colposcopy showed an enhanced sensitivity. Conclusions: Primary HR-HPV cervical cancer screening strategy based on self-sampling with triage of cytology (≥ASCUS) or viral load (≥10 RUL/CO) provides a good balance among sensitivity, specificity for CIN Ⅱ + and CIN Ⅲ + and the number of tests required, referral rates. The efficacy of HR-HPV genotyping combining cytology or viral load secondary screening strategies will have a spiral escalation when HPV 58, 31, 33, 52 are included.

Sorbitol is the primary substrate translocated from source to sink in pear species. Among the many sorbitol transporters (SOTs), some are known to be involved in sorbitol accumulation in fruit; however, their particular roles are unclear. In this study, we examined the transcriptome and metabolome of a variety of pear samples from six time points to identify those SOTs. Similar to previous studies, sorbitol and sucrose differed significantly between the leaf and fruit, and sorbitol was consistently observed at higher concentrations at all time points. Interestingly, we found that sorbitol accumulation in pear fruit was cooperatively mediated by SOT3, SOT6/20, SOT19/21, and SOT22. In particular, the up-regulated SOT6/20 and SOT19/21 in fruit under 1 mg L -1 abscisic acid and 10 mg L -1 indole acetic acid treatments, respectively, resulted in an increased sorbitol concentration. In addition, sorbitol concentration showed positive correlations to fructose and glucose concentrations, indicating a role for sorbitol in the determination of fruit sweetness. Together with the deduced process of sugar biosynthesis, transport, conversion, and accumulation in pear, our study provides a foundation for further research into sugar accumulation processes in pear fruit, contributing to the improvement of fruit quality., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: On Nov 17, 2020, WHO launched a global initiative to accelerate the elimination of cervical cancer through the implementation of HPV vaccination, cervical cancer screening and treatment for precancer and cancer. China has the largest burden of cervical cancer in the world, but only has a national cervical cancer screening program in rural areas since 2009. Here, we aimed to evaluate the effectiveness and cost-effectiveness of cervical cancer screening in urban China, using Shenzhen City as an example., Methods: We use an extensively validated platform ('Policy1-Cervix'), calibrated to data from Shenzhen city and Guandong Province. We evaluated a range of strategies that have previously been implemented as pilot studies in China, or recommended as guidelines within China and globally, spanning primary HPV, cytology and co-testing strategies. We additionally considered alternate triaging methods, age ranges and screening intervals, resulting in 19 algorithms in total., Results: Of the 19 strategies considered, the most effective approach involved primary HPV testing. At 3- to 10-yearly intervals, primary HPV testing reduced the age-standardized cancer mortality rate by 37-71 %. The most cost-effective strategy was 5-yearly primary HPV testing with partial genotyping triage for ages 25-65, discharging to 10-yearly screening for low-risk women (ICER = US$7191/QALYS using 2018 costs; willingness-to-pay threshold<1xGDP [US$9771]). This strategy gave an incidence and mortality reduction of 56 % and 63 %, respectively. This remained the most cost-effective strategy under most conditions in sensitivity analysis., Conclusion: Primary HPV testing would be cost-effective in Shenzhen and could more than halve cervical cancer incidence rates to 6 per 100,000 over the long term. In order to achieve rates below 4 per 100,000, the elimination threshold set by the World Health Organization, vaccination will likely also be necessary., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the value of p16 INK4a detected by p16 INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods: Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16 INK4a technology, among them, 902 cases were offered p16 INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16 INK4a staining. Participants with complete LCT examination, HR-HPV test, p16 INK4a staining and histopathological examination results were included in this study. The performance of p16 INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + ] were analyzed. Results: (1) One-thousand and ninety-seven cases with complete data of p16 INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ) + and 34 cases of HSIL (CIN Ⅲ) + were detected. The positive rate of p16 INK4a in HSIL (CIN Ⅱ) + was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P <0.01). (2) p16 INK4a as primary screening for HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P >0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P <0.05). p16 INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P >0.05). (3) The specificity of LCT adjunctive p16 INK4a for detecting HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + were higher than that of LCT alone or adjunctive HR-HPV ( P <0.01), while the sensitivity were similar ( P >0.05). (4) p16 INK4a staining as secondary screening: p16 INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P <0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P >0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16 INK4a was equally sensitive (88.2% vs 94.1%; P =0.500) and more specific (88.3% vs 83.0%; P <0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P =0.005). Conclusions: For primary screening, p16 INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16 INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16 INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.

Background: Endometriosis is a benign gynecological disease with obviously feature of estrogen-dependence and inflammatory response. The applications of primary endometriotic stromal cells in research of endometriosis are restricted for short life span, dedifferentiation of hormone and cytokine responsiveness. The objective of this study was to establish and characterize immortalized human endometriotic stromal cells (ihESCs)., Methods: The endometriotic samples were from a patient with ovarian endometriosis and the primary endometriotic stromal cells were isolated from the endometriotic tissues. The primary cells were infected by lentivirus to establish telomerase reverse transcriptase (hTERT)-induced immortalized cells. Quantification of mRNA and proteins was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot. CCK-8 assay and EdU labeling assay were assigned to assess the growth of ihESCs. Karyotype assay was performed to detect the chromosomes of ihESCs. Colony formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities., Results: ihESCs continuously overexpressed hTERT via infection of lentivirus and significant extended the life span reaching 31 passages. The morphology, proliferation and karyotype of ihESCs remained unchanged. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins and estrogen/progesterone receptors (ERs and PRs) were unaltered. Furthermore, the treatment of estrogen increased the proliferation and EMT of ihESCs. Lipopolysaccharides (LPS) and IL-1β remarkably induced inflammatory response. The clonogenesis ability of ihESCs was consistent with primary cells, which were much lower than Ishikawa cells. In addition, nude mouse tumorigenicity assay demonstrated that ihESCs were unable to trigger tumor formation., Conclusion: This study established and characterized an immortalized endometriotic stromal cell line that exhibited longer life span and kept the cellular morphology and physiological function as the primary cells. The immortalized cells remained normal feedback to estrogen and inflammatory response. Moreover, the immortalized cells were not available with tumorigenic ability. Therefore, ihESCs would be serviceable as in vitro cell tool to investigate the pathogenesis of endometriosis.

Objective: To analyze the endemic situation of schistosomiasis in a national surveillance site of Yangzhong City, so as to provide the scientific evidence for adjusting the local schistosomiasis control strategy and consolidating the control achievements., Methods: According to the National Schistosomiasis Surveillance Scheme (2014 version), the snail status, Schistosoma japonicum infections in humans and livestock and wild feces contamination were monitored in Zhinan Village, a national schistosomiasis surveillance site in Yangzhong City from 2015 to 2018., Results: Theareasofsnailhabitatsreducedfrom 8.10 hm 2 in 2015 to 2.72 hm 2 in 2018, and the mean density of living snails decreased from 0.27 snails/0.1 m 2 in 2015 to 0.07 snails/0.1 m 2 in 2018 in Zhinan Village; however, no S. japonicum infections were identified in snails during the period from 2015 to 2018. Serological testing for S. japonicum infections was performed in 2 034 local populations and 858 mobile populations from 2015 to 2018, and the sero-prevalence of S. japonicum human infections was 0.59% to 1.98%, with no egg-positives detected. A total of 79 goats were detected for S. japonicum infections from 2015 to 2018, and no egg-positives were found. In addition, no other livestock was found in Zhinan Village from 2015 to 2018, and no wild feces were found in snail habitats., Conclusions: A great success has been achieved in schistosomiasis control in Yangzhong City; however, there are still snails breeding in the city. Monitoring of the risk factors pertaining to schistosomiasis transmission should be further intensified to consolidate the control achievements.

Objective: Evaluation of the clinical value of the BioPerfectus multiplex real time (BMRT)-HPV for cervical cancer screening. Methods: Physician-collected specimens of 1 495 women who were positive of Cobas 4800 HPV (Cobas-HPV), HPV genotyping based on SEQ uencing (SEQ-HPV), and (or) cytology ≥low grade squamous intraepithelial lesion (LSIL) in the primary screening of Chinese Multiple-center Screening Trial (CHIMUST), and 2 990 women selected from those who were negative of primary screening in the same project through nested control randomization with age-matching were tested for BMRT-HPV, which reported type-specific viral loads/10 000 cells in each specimen. With comparing to Cobas-HPV results and taking cervical histopathological diagnosis as the endpoint, the concordance of high-risk (HR)-HPV subtypes among the three assays was explored ,and the sensitivity and specificity of BMRT-HPV for cervical cancer screening were evaluated. Results: (1) The overall agreenment of HR-HPV subtypes between BMRT-HPV and Cobas-HPV, or SEQ-HPV test sample was 94.8%, 94.4%, with Kappa values 0.827, 0.814. (2) The sensitivity and specificity for cervical intraepithelial neoplasia (CIN) Ⅱ + of BMRT-HPV, Cobas-HPV and SEQ-HPV were 92.62%, 94.26%, 93.44% and 84.67%, 83.25%, 82.76%, respectively. There were no significant difference in sensitivity among the three HPV assays (all P >0.05), but the specificity of BMRT-HPV for CIN Ⅱ + was higher than those of Cobas-HPV and SEQ-HPV ( P <0.01). The sensitivity for CIN Ⅲ + of three HPV assays were all 100.00%, and the specificity for CIN Ⅲ + of BMRT-HPV was higher than those of Cobas-HPV and SEQ-HPV (83.40% vs 81.95%, 83.40% vs 81.50%; P <0.01). The number of pathological examinations of colposcopy for cervical biopsy detected in 1 case of CIN Ⅱ + or CIN Ⅲ + in BMRT-HPV was less than those in Cobas-HPV and SEQ-HPV ( P <0.01). When using HPV 16/18 + cytology ≥atypical squamous cell of undetermined signification (ASCUS) to triage HPV positive women among three assays, there was no different in the sensitivities of detecting CIN Ⅱ + and CIN Ⅲ + ( P >0.05). The specificity BMRT-HPV was slightly higher than those in Cobas-HPV or SEQ-HPV (all P <0.05), and the colposcopy referral rate was lower than those in Cobas-HPV and SEQ-HPV (all P <0.05). Conclusions: BMRT-HPV is as sensitive as Cobas-HPV or SEQ-HPV for primary cervical cancer screening, and has higher specificity. Therefore it could be used as a primary screening method for cervical cancer, which is worthy of clinical application.

Endometriosis is a benign gynaecological disease appearing with pelvic pain, rising dysmenorrhoea and infertility seriously impacting on 10% of reproductive-age females. This research attempts to demonstrate the function and molecular mechanism of RhoA/ROCK pathway on epithelial-mesenchymal transition (EMT) and proliferation in endometriosis. The expression of Rho family was abnormally changed in endometriotic lesions; in particular, RhoA and ROCK1/2 were significantly elevated. Overexpression of RhoA in human eutopic endometrial epithelial cells (eutopic EECs) enhanced the cell mobility, epithelial-mesenchymal transition (EMT) and proliferation, and RhoA knockdown exhibited the opposite function. Oestrogen up-regulated the RhoA activity and expression of RhoA and ROCK1/2. RhoA overexpression reinforced the effect of oestrogen on promoting EMT and proliferation, and RhoA knockdown impaired the effect of oestrogen. oestrogen receptor α (ERα) was involved with the regulation of oestrogen on EMT and proliferation and up-regulated RhoA activity and expression of RhoA and ROCK1/2. The function of ERα was modulated by the change in RhoA expression. Furthermore, phosphorylated ERK that was enhanced by oestrogen and ERα promoted the protein expression of RhoA/ROCK pathway. Endometriosis mouse model revealed that oestrogen enhanced the size and weight of endometriotic lesions. The expression of RhoA and phosphorylated ERK in mouse endometriotic lesions was significantly elevated by oestrogen. We conclude that abnormal activated RhoA/ROCK pathway in endometriosis is responsible for the function of oestrogen/ERα/ERK signalling, which promoted EMT and proliferation and resulted in the development of endometriosis., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: To investigate the use of p16(INK4a) immuno-stained cytology as the primary screening for cervical cancer prevention. Methods: From March to August 2018, 902 women from Shenzhen and surrounding area were recruited for cervical cancer screening with ThinPrep Cytologic Test (TCT), cobas4800 HPV test, and p16(INK4a) co-test. Colpo/biopsies were performed using the point of interest biopsy protocol of directed and random cervical biopsies plus endocervical curettage for all women, any of whose tests was positive. Two senior cytopathologists interpreted TCT and p16(INK4a) test. The performance of p16(INK4a) for early detection of CIN2+ and inter-observer reproducibility of the interpretation of p16(INK4a) were evaluated. Results: The positive rates of HPV test, p16(INK4a) co-test and TCT diagnosed as LSIL/AGC or higher grade were 8.1% (73/902), 6.8% (61/902) and 4.7% (42/902), respectively. Colposcopy referring rate was 79.6% (109/137), among which 10 cases were diagnosed as CIN2+ (5 cases of CIN2 and 5 cases of CIN3). The sensitivity and specificity for CIN2+ of p16(INK4a) test, TCT (LSIL/AGC or higher grade) and HPV test were 90.0%, 80.0%, 100.0% and 90.9%, 91.9%, 82.5%, respectively. Compared to TCT and HPV test, there was no significant difference in sensitivity and specificity between p16(INK4a) and TCT/HPV test ( P> 0.05). The Kappa value of the 2 cytopathologists in interpreting p16(INK4a) and TCT was 0.944 and 0.425, respectively ( P< 0.05). Conclusions: p16(INK4a) for cervical cancer screening is equally sensitive to HPV test and specific to TCT while subjective difference of cytopathologists' interpretation of p16(INK4a) is small. Therefore, p16(INK4a) can be used as a new cervical cancer screen method for its better diagnostic performance.

A new benzylated alkamide, N -(3,4-dimethoxybenzyl)-9 Z -oleamide ( 1 ), along with two known ones ( 2 and 3 ) were isolated from the roots of Lepidium meyenii collected from Lijiang, Yunnan Province of China. Their structures were elucidated by extensive spectroscopic analyses and the new compound further confirmed by a one-step synthesis. All the isolated alkamides were evaluated for their cytotoxicity against five human cancer cell lines. However, no significant activities were detected at concentrations up to 40  μ M.

Background: To evaluate the clinical significance of low-frequency electrical stimulation in preventing urinary retention after radical hysterectomy., Methods: A total of 91 women with stage IA2-IB2 cervical cancer, who were treated with radical hysterectomy and lymphadenectomy from January 2009 to December 2012, were enrolled into this study and were randomly divided into two groups: trail group (48 cases) and control group (43 cases). Traditional bladder function training and low-frequency electrical stimulation were conducted in the trail group, while patients in the control group were only treated by traditional bladder training. The general condition, rate of urinary retention, and muscle strength grades of pelvic floor muscle in the perioperative period were compared between these two groups., Results: The incidence of postoperative urinary retention in the electrical stimulation group was 10.41%, significantly lower than that in the control group (44.18%), and the difference was statistically significant (P < 0.01). The duration of postoperative fever and use of antibiotics were almost the same between these two groups. Eleven days after surgery, the difference in grades of the pelvic floor muscle between these two groups was not statistically significant. However, 14 days after the operation, grades of the pelvic floor muscle were significantly higher in the trail group than in the control group, and the difference was statistically significant (P < 0.01). In addition, although there was no significant difference between the two groups with different parameters (P = 0.782), the incidence of urinary retention was lower in the endorphins analgesia program group than in the neuromuscular repair program group (9.09% < 11.54%)., Conclusion: Low-frequency electrical stimulation is more effective than conventional intervention in preventing urinary retention after radical hysterectomy. It also intensifies the recovery of pelvic muscle strength.

Objective: To explore the relationship between cervical lesions and high risk HPV (HR-HPV) viral load reflected by the cycle threshold (Ct) values of Cobas 4800 HPV (Cobas 4800) system. Methods: From August 2016 to September 2017, 7 000 women from Shenzhen, were recruited for cervical cancer screening with Cobas 4800 system and cytology co-test. Colposcope biopsies were performed on women who were positive of HPV 16, 18, and positive of HPV types other than 16,18 with cytology [≥ atypical squamous cell of undetermined signification (ASCUS)], or HPV negative but abnormal of cytology [≥ low grade squamous intraepithelial lesion (LSIL)]. The Ct values of HPV 16, 18 and all combined other types coming from Cobas 4800 system were used as an indicator of viral load to analyze the relationship between type-specific HPV load and the cervical lesions. Results: (1) Among the 7 000 screening women, 370 cases were positive for cervical cancer screening, 325 of them underwent colposcope biopsies, and coloposcopy referred rate was 87.8% (325/370). Among 325 women undergoing cervical biopsy, pathological diagnosis was 119 cases of normal cervical cervix, 151 cases of LSIL, and 55 cases of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL(+); including 53 cases of HSIL, 1 case of cervical adenocarcinoma, and 1 case of cervical squamous cell carcinoma). (2) The Ct value of HPV 16 was inversely correlated with the upgrading of the lesions ( r =-0.617, P =0.000), and significant different among normal cervix,LSIL and HSIL(+) (35.4±4.5 vs 31.0±6.0 vs 26.5±4.0; F =25.537, P =0.000). There was no correlation between Ct value of HPV 18 and cervical lesions ( r =-0.021, P =0.902). The Ct value of other 12 HPV types was statistically difference among normal normal cervix, HSIL(+) and cervicitis (33.0±5.3 vs 29.9±7.2 vs 29.8±5.8; F =5.087, P =0.007). Among them, LSIL and HSIL(+) were significantly lower than normal cervix ( P <0.05), but there was no significant difference between LSIL and HSIL(+) ( P >0.05). Conclusion: The Ct value of HPV 16 detecting in Cobas 4800 system as an indicator of virus load obviously correlates with different grades of cervical lesions, therefore could be a reference of cervical lesion existence and an indicator of lesion prognosis.

Objective: To evaluate the feasibility of the BioPerfectus multiplex real time (BMRT) HPV assay for self-sample cervical cancer screening. Methods: Eight hundreds and thirty-nine self-collected and physician-obtained DNA samples from the Shenzhen cervical cancer screening trial Ⅳ(SHENCCAST-Ⅳ) study collected samples for cervical cancer screening during June 2013 to September 2014 were detected by BMRT HPV assay to evaluate the screening efficacy. Results: A total of the 839 women who were screened, 804 with complete BMRT HPV data was included in the study, and average age was (46±7) years. Of the 804 women, the positive rates of 14 high-risk HPV genotypes (including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 subtype) of self-sample and physician-obtained samples were 12.2% (98/804) and 12.8% (103/804), respectively (χ(2)=0.14, P =0.71). Self-collected samples with HPV-positive had significantly more cells (median 19 901.0) than physician-obtained samples (median 1 778.4), and there was statistically significant difference ( Z =-7.61, P <0.01). The degree of agreement between self-sample and physician-obtained samples of HPV 16, HPV 18 and other 12 high risk HPV genotype was 99.8%, 100.0% and 96.1%, respectively. And the consistent Kappa value was 0.95, 1.00 and 0.81, respectively. Of 804 samples, there were 6 cervical intraepithelial neoplasia (CIN)Ⅱ(+) cases. There were no missed CINⅡ(+) cases by BMRT HPV assay. Conclusion: BMRT HPV assay is feasible for self-sample cervical cancer screening.

N 6 -methyladenosine (m 6 A) is the most abundant-internal modification of eukaryotic mRNA. m 6 A can be installed and removed by specific enzymes. The "writer," "eraser," and "reader" of m 6 A modification have been reported. These discoveries facilitate our understanding of the functional significance of m 6 A. m 6 A plays an essential role in diverse biological processes by recruiting the corresponding YTH domain-containing proteins, as well as recruiting additional translation initiation factors. Here, we provide an update on the various aspects of YTH domain-containing proteins, including an introduction to the YTH domain, the categories, distribution in cells, and biological roles of YTH proteins. Then we focus on the mechanisms that YTH proteins recognize m 6 A and mediate the fate of methylated-RNAs in eukaryotic cells.

The endoplasmic reticulum (ER) produces the vast majority of all proteins secreted into the extracellular space, including hormones and cytokines, as well as cell surface receptors and other proteins which interact with the environment. Accordingly, this organelle controls essentially all vital links to a cell's external milieu, responding to systemic metabolic, inflammatory, endocrine, and mechanical stimuli. The central role the ER plays in meeting protein synthetic and quality control requirements in the face of such demands is matched by an extensive and versatile ER stress response signaling network. ROS mediate several critical aspects of this response. Nox4, an ER resident capable of producing ROS, acts as a proximal signaling intermediate to transduce ER stress-related conditions to the unfolded protein response, a homeostatic corrective mechanism. However, chronic ER stress caused by unrelenting internal or external demands produces a secondary rise in ROS, generally resulting in cell death. Sorting out the involvement of ROS at different levels of the ER stress response in specific cell types is key to understanding the molecular basis for chronic diseases such as atherosclerosis, hypertension, and diabetes. Here, we provide an overview of ER stress signaling with an emphasis on the role of ROS., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Endometriosis is an estrogen-dependent disease associated with pain and infertility. The objective of this study was to determine the expression of ZEB1 in endometriosis and its role in 17β-estradiol (E2)-induced epithelial-mesenchymal transition (EMT). 25 patients with endometriosis and 16 endometriosis-free patients were recruited for the study. Tissue expression of EMT makers was investigated by immunohistochemistry, then the expression of ZEB1 was quantified by qRT-PCR, immunohistochemistry, and western blot. The proliferation, DNA replication, and migration and invasion in ZEB1 knockdown Ishikawa cells were further respectively performed by MTS, Edu, wound healing and transwell assays. Luciferase assay was used to measure the ZEB1 promoter activity. Our results show that protein levels of E-cadherin and Keratin 18 decreased in endometriotic tissues. Meanwhile the expressions of ZEB1, Vimentin, and N-cadherin were significantly increased in endometriotic tissues. Down-regulation of ZEB1 inhibited Ishikawa cells proliferation, migration, invasion and EMT. E2 promoted the expression of ZEB1 through the ER genomic pathway, which contributed to the EMT process. The -1401 bp - -1901 bp region in the ZEB1 promoter was the main target of the E2 activity. The present results suggest that a high expression of ZEB1 plays an important role in the pathogenesis of endometriosis, and it may serve as a potential therapeutic target for endometriosis., Competing Interests: None., (IJCEP Copyright © 2018.)

Objective: Epithelial-mesenchymal transition (EMT) is essential for embryogenesis, fibrosis, and tumor metastasis. Aberrant EMT phenomenon has been reported in endometriotic tissues of patients with endometriosis (EM). In this study, we further investigated the molecular mechanism of which lipoxin A 4 (LXA 4 ) suppresses estrogen (E 2 )-induced EMT in EM., Study Design: The EMT markers were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot in eutopic endometrial epithelial cells (EECs) or investigated by immunohistochemistry and qRT-PCR in endometriotic lesion of EM mice. The invasion and migration under different treatments were assessed by transwell assays with or without Matrigel. The messenger RNA (mRNA) and activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were determined by qRT-PCR and gelatin zymography, respectively. Luciferase reporter assay was used to measure the activity of zinc finger E-box binding homeobox 1(ZEB1) promoter. The level of E 2 in endometriotic tissues was assessed by enzyme-linked immunosorbent assay., Results: In eutopic EECs, stimulatory effects of E 2 on EMT progress, migration, and invasion were all diminished by LXA 4 . Lipoxin A 4 reduced E 2 -induced ZEB1 promoter activity. Lipoxin A 4 also attenuated the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase induced by E 2 . Co-incubation with Boc-2 rather than DMF antagonized the influence of LXA 4 . Animal experiments showed that LXA 4 inhibited the EMT progress, MMP expression, and proteinase activities of endometriotic lesion in an LXA 4 receptor (ALXR) manner, which suppressed the progression of EM. ZEB1 mRNA expression was upregulated and well correlated with E 2 level in human endometrium., Conclusion: Lipoxin A 4 suppresses E 2 -induced EMT via ALXR-dependent manner in eutopic EECs, which reveals a novel biological effect of LXA 4 in EM.

Objective: To explore the human papilomavirus (HPV) genotypes and epithelial thickness of invisible cervical intraepithelial neoplasia Ⅲ (CIN Ⅲ) under colposcopy. Methods: One hundred and sixty-nine biopsies from 93 patients with a final diagnosis of CIN Ⅲ were extracted from the Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST Ⅱ) . The SHENCCAST Ⅱ was conducted from 2009 to 2010. All the cervical blocks from these patients were re-cut and placed on 6 slides, i.e. sandwich model, with the top and bottom sections being stained with HE, the top second be processed for other studies, 3 sections for HPV genotypes by matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) assay. The thickness of squamous epithelium of CIN Ⅲ was measured by a microscope (×10) after re-cut. Colposcope directed CIN Ⅲ biopsies positively was defined as visible CIN Ⅲ, while random CIN Ⅲ biopsies positively was defined as invisible CIN Ⅲ. Results: HPV16 positivity was 37.2% (16/43) and 55.6% (70/126) between invisible and visible CIN Ⅲ biopsies, respectively (χ(2)=4.318, P =0.038) . Forty-nine cases of the 93 CIN Ⅲ patients were HPV16 positive, while 44 of them non-HPV16 positive. The proportion of patients with ≥45 years of age for other non-HPV16 positive 40.9% (18/44) was significantly higher than that HPV16 positive 20.4% (10/49; χ(2)=4.630, P =0.031) . Patients with HPV16 positive were more likely to have lesions ≥1 quadrant (χ(2)=7.786, P =0.005) than other non-HPV16 positive. Compared the average epithelium thickness of invisible CIN Ⅲ tissue (140±12) μm, the average epithelium thickness of visible CIN Ⅲ tissue (161±9) μm was thicker. There was statistical difference between two groups ( t =4.383, P =0.038). The mean average epithelial thickness of CIN Ⅲ with HPV16 positive (172±11) μm was thicker than that the mean average epithelial thickness of CIN Ⅲ with non-HPV16 positive (130±10) μm ( t =4.784, P =0.031) . Conclusions: Invisible lesions is difficult to identify under colposcopy and is related to non-HPV16 positive, small lesion size and thinner squamous epithelium. For non-HPV16 positive or older women should be performed colposcope directed biopsies and randomly multi-sites biopsies by colopscopy, which may be helpful to improve the detection of CIN Ⅲ and to reduce miss diagnosis.

Objective: To determine the morbidity of cervical intraepithelial neoplasia 2+ (CIN2+ ) and CIN3+ of different human papillomavirus(HPV) subtype infection combined with different cytology status. Methods: The Shenzhen Cervical Cancer Screening Trial Ⅰ & Ⅱ (SHENCCASTⅠ&Ⅱ) are population-based cross-sectional cervical cancer screening studis conducted in Shenzhen and surrounding area from 2008 to 2010. A total of 12 097 women who aged 25-59 years were included in the analysis. All of these women were detected by liquid-based cytology test and several high-risk HPV-DNA tests. The ones with HPV positive or atypical squamous cells of undetermined sign (ASC-US) were sequentially conducted by cervical biopsy vaginoscopy. Finally, 10 805 samples with complete data of hybrid capture 2(HC2), the polymerase chain reaction-based matrix-assisted laser desorption/ionization time-of-flight assay (MALDI-TOF), HPV genotyping detection, cytology and pathology results were analyzed. Results: The top 6 infection rates of HR-HPV in CIN2+ and CIN3+ were HPV16, HPV52, HPV58, HPV33, HPV31, HPV18. The highest constituent ratio of cytology in CIN2+ and CIN3+ was high grade squamous intraepithelial lesion(HSIL). The morbidities of CIN2+ of patients infected with HPV16, HPV31, HPV58, HPV33, HPV18, HPV52 were 41.3%, 31.5%, 30.6%, 28.7%, 28.2%, 17.7%, respectively, while the morbidities of CIN3+ of those were 33.5%, 20.5%, 19.4%, 15.7%, 19.2%, 8.3%, respectively.The morbidities of CIN2+ in negative intraepithelial lesion or malignancy (NILM), ASC-US, low grade squamous intraepithelial lesion (LSIL), atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (ASC-H), high grade squamous intraepithelial lesion (HSIL), atypical glandular cell (AGC) samples were 0.4%, 6.9%, 11.1%, 36.4%, 82.0%, 16.7%, respectively, while the morbidities of CIN3+ of those were 0.2%, 3.1%, 4.2%, 22.7%, 64.8%, 0.0%, respectively. The morbidities of CIN2+ in NILM combined with HPV16, HPV18, HPV31, HPV33 infection were 12.6%, 13.3%, 15.8% and 11.5%, respectively, while the morbidities of CIN3+ of those were 10.3%, 11.1%, 7.9% and 7.7%, respectively.The morbidities of CIN2+ and CIN3+ in ASC-US combining with hrHPV infection were high, and the top 6 subtypes associated with high risk of CIN2+ were HPV31 (35.7%), HPV33 (26.9%), HPV16 (26.5%), HPV58 (22.4%), HPV52 (18.6%), HPV68 (15.4%), while those associated with high risk of CIN3+ were HPV16 (20.4%), HPV31 (14.3%), HPV33 (11.5%), HPV58 (8.6%), HPV68 (7.7%), HPV52 (5.8%). Conclusions: Cytology combined with HPV genotyping detection can more effectively estimate the morbidity risks of CIN2+ and CIN3+ . Both high prevalence rates and high risks associated with CIN2+ and CIN3+ of HPV31, HPV33, HPV52 and HPV58 are observed. NILM and ASC-US status combined with these subtypes mentioned above are advised to be conducted by colposcopy.

Objectives: To develop and evaluate the efficacy and feasibility of Intracapsular Rotary-cut Procedure (IRCP) in laparoscopic myomectomy (LM)., Study Design: It is a retrospective study conducted in Peking University Shenzhen Hospital (PUSH) in Shenzhen, China. A total of 96 patients who were treated with LM because of big and moderate size of myomas in PUSH from January 2013 and December 2015 were enrolled in this study. Among them 35 were managed with IRCP -integrated LM as the study group, while the other 61 were treated with normal LM as the control group. The core steps of IRCP include minimized uterine incision, rotary cuttings in the fibroid inside the pseudocapsule, and preserving the fibers and vessels of the fibroid pseudocapsule. The operation data and outcome variables of each patient in the two groups were collected and compared to evaluate the efficacy and feasibility of this new improved surgery procedure., Results: The ages, body mass indexes, main indication for myomectomy, and the diameters, numbers and types of the fibroids of patients in the two groups were similar. There is no significant difference in enucleation time and days of postoperative in-hospital staying between the two groups. In comparison with normal LM, application of IRCP significantly reduced the length of uterine incisions (P=0.000), the overall time of operations (P=0.001), and the time for uterine cavity suturing (P=0.000), and application of IRCP was also associated with less operation bleeding (P=0.003) and postoperative hemoglobin dropping (P=0.001). Five cases (8.2%) in the control group were referred to laparotomy, while no case was done so in the study group. No patient in the study group needed blood transfusion but six patients (9.8%) in the control group did. Follow-up to all the patients showed no uterine malignant tumor., Conclusions: Our study provided strong supportive evidences showing that Intracapsular Rotary-cut Procedures is safe and practicable. The less uterine incision length, less surgery time, and less bleeding than the normal LM procedures all suggests that IRCP should be adopted in LM for facilitation to the operation procedures, minimization of operative invasiveness, and protection to patients' infertility., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the in vivo osseointegration of implants with hydrophobic antimicrobial GL13K-peptide coating in rabbit femoral condyles by micro-CT and histological analysis. Six male Japanese Rabbits (4 months old and weighing 2.5 kg each) were included in this study. Twelve implants (3.75 mm wide, 7 mm long) were randomly distributed in two groups, with six implants in the experimental group coated with GL13K peptide and six implants in the control group without surface coating. Each implant in the test and the control group was randomly implanted in the left or right side of femoral condyles. On one side randomly-selected of the femur, each rabbit received a drill that was left without implant as control for the natural healing of bone. After 3 weeks of healing radiographic evaluation of the implant sites was taken. After 6 weeks of healing, rabbits were sacrificed for evaluation of the short-term osseointegration of the dental implants using digital radiography, micro-CT and histology analysis. To perform evaluation of osseointegration, implant location and group was double blinded for surgeon and histology/radiology researcher. Two rabbits died of wound infection in sites with non-coated implants 2 weeks after surgery. Thus, at least four rabbits per group survived after 6 weeks of healing. The wounds healed without suppuration and inflammation. No implant was loose after 6 weeks of healing. Radiography observations showed good osseointegration after 3 and 6 weeks postoperatively, which proved that the tissues followed a natural healing process. Micro-CT reconstruction and analysis showed that there was no statistically significant difference (P > 0.05) in volume of bone around the implant between implants coated with GL13K peptide and implants without coating. Histomorphometric analysis also showed that the mineralized bone area was no statistically different (P > 0.05) between implants coated with GL13K peptide and implants without coating. This study demonstrates that titanium dental implants with an antimicrobial GL13K coating enables in vivo implant osseointegration at similar bone growth rates than gold-standard non-coated dental implants up to 6 weeks of implantation in rabbit femurs.

Background: The human papillomavirus (HPV) vaccine is recommended for male and female recipients aged 9-26 years, and is effective in preventing HPV infection and cancer precursors. However, there is variability in immunogenicity among recipients as measured by anti-HPV geometric mean titers. In this study, we explored the effect of stress level on the immunogenicity of the HPV vaccine among college age males., Methods: 220 males aged 18-25 y were randomly assigned to 6-month (0, 2, and 6) and 12-month (0, 2, and 12) dosing schedules. Antibody titers were measured before the first dose and 2-6 weeks following the final dose. We recorded participants' age and stress level, based on a 4-item Perceived Stress Scale (PSS-4) questionnaire., Results: The average age of participants was 21.3 y old. Inspection of titers by quartile on the stress scale generally showed highest titers with highest stress. Spearman correlation coefficients revealed significant correlation between stress and titers for HPV-6, 16, and 18 but not for HPV-16 in the group of 6-month dosing schedule; no associations were found for the 12-month dosing schedule. For most strains, linear regression revealed significant (P > 0.05) associations on antibody titer for categorical age and dosing schedule but not stress., Conclusion: The evidence is mixed for an association between stress and HPV vaccine response for the 6-month dosing schedule, but no association was found for stress for the 12-month dosing schedule. Further investigations with larger and more diverse population groups are needed to explore the association between stress level and vaccine immunogenicity.

Aim: Lipoxin A 4 (LXA 4 ) can function as an endogenous 'breaking signal' in inflammation and plays an important role in the progression of endometriosis. The proteome responses to interleukin-1β (IL-1β) or LXA 4 in human endometriotic stromal cells (ESC) are not well understood., Methods: In this study, primary ESC were cultured from ovarian endometriosis tissue. Three groups were established: the control group; the IL-1β stimulation group; and the IL-1β and LXA 4 incubation group. Proteins were assessed on 2-D polyacrylamide gel electrophoresis (2D-PAGE), and differentially expressed protein spots were further identified on matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MALDI-TOF-MS). Wound healing and transwell assays were performed to assess the migration and invasion of ESC after treatment., Results: In total, 40 differentially expressed protein spots were identified successfully on MALDI-TOF-MS. The proteins identified were related to cell structure, metabolism, signal transduction, protein synthesis and membrane structure, processes that may be involved in the development of endometriosis. Vinculin and IL-4 were further analyzed on western blot and quantitative real-time polymerase chain reaction. Moreover, LXA 4 could suppress the migration and invasion of ESC induced by IL-1β., Conclusion: LXA 4 may inhibit the progression of endometriosis partly by lowering or raising the effect of IL-1β, mediated via some inflammation-related proteins (e.g. vinculin) and immune response-related protein (e.g. IL-4) in vitro., (© 2016 Japan Society of Obstetrics and Gynecology.)

Objectives: In response to endoplasmic reticulum (ER) stress, endothelial cells initiate corrective pathways such as the unfolded protein response. Recent studies suggest that reactive oxygen species produced on the ER may participate in homeostatic signaling through Ras in response to ER stress. We sought to identify mechanisms responsible for this focal signaling pathway., Approach and Results: In endothelial cells, we found that ER stress induced by tunicamycin activates the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase Nox4 focally on the ER surface but not on the plasma membrane. Ras activation is also restricted to the ER, occurs downstream of Nox4, and is required for activation of the unfolded protein response. In contrast, treatment with the growth factor VEGF (vascular endothelial growth factor) results in Ras activation and reactive oxygen species production confined instead to the plasma membrane and not to the ER, demonstrating local coupling of reactive oxygen species and Ras signals. We further identify the calcium-responsive, ER-resident guanyl exchange factors RasGRF1 and RasGRF2 as novel upstream mediators linking Nox4 with Ras activation in response to ER stress. Oxidation of the sarcoendoplasmic reticulum calcium ATPase and increases in cytosolic calcium caused by ER stress are blocked by Nox4 knockdown, and reduction in cytosolic free calcium prevents both Ras activation and the unfolded protein response., Conclusions: ER stress triggers a localized signaling module on the ER surface involving Nox4-dependent calcium mobilization, which directs local Ras activation through ER-associated, calcium-responsive RasGRF., (© 2016 American Heart Association, Inc.)

Tissue cells respond to changes in tensional forces with proliferation or death through the control of RhoA. However, the response coupling mechanisms that link force with RhoA activation are poorly understood. We found that tension applied to fibronectin-coated microbeads caused recruitment of all three isoforms of the Shc adapter (p66 Shc , p52 Shc , and p46 Shc ) to adhesion complexes. The Shc PTB domain was necessary and sufficient for this recruitment, and screening studies revealed the direct interactions with the FERM domain of focal adhesion kinase (FAK) that were required for Shc translocation to adhesion complexes. The FAK/p66 Shc complex specifically bound and activated the Rho guanyl exchange factors (GEFs) p115-RhoGEF and GEF-H1, leading to tension-induced RhoA activation. In contrast, the FAK/p52 Shc complex bound SOS1 but not the Rho GEFs to mediate tension-induced Ras activation. Nuclear translocation and activation of the YAP/TAZ transcription factors on firm substrates required the FAK/p66 Shc /Rho GEF complex, and both proliferation on firm substrates and anoikis in suspension required signaling through p66 Shc and its associated Rho GEFs. These studies reveal the binary and exclusive assignment of p66 Shc and p52 Shc to tension-induced Rho or Ras signals, respectively, and suggest an integrated role for the two Shc isoforms in coordinating the cellular response to mechanical stimuli., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The aim of this study was to evaluate the performance of three new high-risk human papillomavirus (HPV) assays for primary cervical cancer screening, by using self-collected samples, and to identify an HPV assay that could overcome the major obstacles faced during large-scale population-based screening. Two hundred and ten women showing abnormal cervical cytology (and referred for a colposcopy) were recruited in this study. Self-collected samples obtained from all women were tested with the Cobas, Seq, and BioPerfectus Multiplex Real Time HPV assays; simultaneously, clinician-collected samples (from the same women) were tested with the gold-standard Cobas HPV assay. The results of all the assays were consistent. The sensitivity, positive predictive value, and negative predictive value for cervical intraepithelial neoplasia 2+ (CIN2+) and CIN3+ were comparable between the self-collected samples tested with the three new assays and the clinician-collected samples tested with the Cobas HPV assay (P > 0.05). The single-genotype HPV load per sample did not differ significantly between the self- and clinician-collected samples (P = 0.195). In conclusion, the results of this study demonstrated the applicability of the three new HPV assays for primary cervical cancer screening based on self-collection.

Chemotherapy can lead to the loss of fertility and premature ovarian failure in young women who suffer from malignant diseases. Freezing ovarian tissue by vitrification allows for the preservation of a large number of follicles prior to treatment, yet no established protocols have been optimized with respect to the vitrification solution. The aim of the present study was to evaluate the early stage of human ovarian tissue xenotransplantated onto the chick embryo chorioallantoic membrane after vitrification, and to determine the effect of different vitrification solutions on ovarian tissue quality-as defined by morphology and viability of follicles, neovascularization, cell proliferation, and apoptosis. Each vitrification protocol had a different impact on ovarian tissue at the early transplantation stage; one process using the lowest concentrations of ethylene glycol and dimethylsulfoxide, plus sucrose, demonstrated a moderate advantage compared to the other protocols. We also demonstrated that the chorioallantoic membrane model can be a useful alternative for short-term xenotransplantation studies of angiogenesis into human ovarian cortical tissue., (© 2016 Wiley Periodicals, Inc.)

Objective: To master the changes of schistosomiasis epidemic situation in national surveillance sites of Zhenjiang City, Jiangsu Province., Methods: According to the scheme of the national schistosomiasis surveillance, the Shicheng Village of Yangzhong County and Sanzhou Village of Dantu District were selected as the national schistosomiasis surveillance sites, and from 2005 to 2010, the schistosomiasis morbidity and Oncomelania hupensis status were surveyed and the results were analyzed statistically., Results: In 2010, in the Shicheng Village, the reduction rates of mean living snail density, infected snail density, area with infected snails, and positive blood tests in residents were 98.4%, 0, 0, 71.8% respectively, and in the Sanzhou Village, the reduction rates were 70.4%, 100%, 100% and 81.5%, respectively compared with those in 2005. No acute infections were found in the 2 villages during the period of 6 consecutive years., Conclusion: In the national surveillance sites of Zhenjiang City, the schistosomiasis morbidity has been effectively controlled. However, the areas with snails change little. Therefore, the comprehensive management of snail environment in the marshland should be strengthened in the future.

Objective: To investigate role of Zinc finger E-box binding homeobox 1 (ZEB1) in cervical cancer tissue (squamous cell carcinoma, SCC)., Design: Exploratory study., Setting: University hospital., Patient(s): Sixty patients with SCC, including stage CINIII (n = 10), IB1 (n = 10), IB2 (n = 10), IIA1 (n = 10), IIA2 (n = 10), and IIB (n = 10) were studied., Intervention(s): Caski cells were transfected with recombinant shZEB1 lentivirus or shCtrl lentivirus to generate stable ZEB1-knockdown Caski cells., Main Outcome Measure(s): ZEB1 expression was analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry in cervical cancer tissues. ZEB1 expression in Caski cells was down-regulated by short-hairpin RNA (shRNA) interference, and changes in ZEB1 expression corresponded with changes in the proliferation and migratory ability of Caski cells., Result(s): Quantitative real-time polymerase chain reaction and immunohistochemistry results revealed that ZEB1 expression and the ratio of Vimentin to E-cadherin were high in 27 of 50 SCC patients and correlated with advanced International Federation of Gynecology and Obstetrics stage, tumor size >4 cm, and parametrial invasion. However, the expression of ZEB1 in cervical cancer tissue was independent of age and SCC antigen level. Transfection of ZEB1 shRNA in Caski cells significantly decreased the messenger RNA and protein expression of ZEB1, parallel with increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker Vimentin. Furthermore, the proliferation and migratory ability of Caski cells were significantly lower in the transfected group than in the nontransfected control group., Conclusion(s): Down-regulation of ZEB1 expression may protect the invasive front of the tumors from converting to a mesenchymal phenotype by reducing the proliferation and motility of cervical cancer cells, suggesting that ZEB1 might be a potential therapeutic target for SCC., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This study investigated the incidences of urinary incontinence and pelvic organ prolapse as well as pelvic floor muscle strength after cesarean section and vaginal delivery. From June 2010 to July 2011, 149 puerpera in Shenzhen Hospital, Peking University, were divided into the cesarean section group (N = 66) and the vaginal delivery group (N = 83). Postpartum urinary incontinence analysis, pelvic examination, and pelvic muscle contraction analysis using the PHENIX neuromuscular therapy instrument were performed to compare urinary incontinence, pelvic organ prolapse, and pelvic floor muscle condition between the 2 groups. The incidences of urinary incontinence in the cesarean and vaginal delivery groups were 9.09% (6/66) and 16.87% (14/83), respectively (P > 0.05); the incidences of pelvic organ prolapse were 53.03% (35/66) and 86.75% (72/83), respectively (P < 0.05). There was no significant difference in pelvic muscle pressure or electrophysiological examination results between the 2 groups (P > 0.05). Hence, cesarean section has a protective effect on early postpartum pelvic organ prolapse, but the delivery modes do not differ significantly with respect to the incidence of postpartum urinary incontinence or pelvic muscle floor muscle strength.