Among gynecologic malignancies, ovarian cancer is the most lethal, primarily due to its insidious early symptoms, lack of effective screening methods, and high risk of recurrence. It poses substantial challenges to clinical diagnosis and treatment. In recent years, the clinical application of poly ADP-ribose polymerase inhibitors has promoted a comprehensive management model that integrates targeted therapy with conventional treatments. This review, aiming to provide new perspectives and approaches for future research, summarizes the high-risk factors and first-line treatment strategies for ovarian cancer. Further studies should focus on optimizing personalized treatment strategies and exploring novel targeted therapies to improve patient survival outcomes.

Objective:To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity.Methods:The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity.Results:Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation ( P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells ( P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group ( P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group ( P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group ( P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group ( P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group ( P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group ( P＜0.05). Conclusion:Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.

Objective:To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity.Methods:The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity.Results:Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation ( P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells ( P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group ( P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group ( P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group ( P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group ( P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group ( P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group ( P＜0.05). Conclusion:Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.

Objective To explore the effects of small incision in situ release on surgical indications,nerve conduction velocity and upper limb function in patients with carpal tunnel syndrome(CTS).Methods A total of 100 CTS patients admitted to our hospital from January 2018 to January 2022 were selected,they were randomly divided into the control group(50 cases,treated with traditional carpal tunnel release)and the observation group(50 cases,treated with small incision in situ release),the clinical data of CTS patients were collected and surgical indications,nerve conduction velocity,upper limb function and the incidence of complications were compared between the two groups.Results The total effective rate was 98.00％in the observation group and 84.00％in the control group(P＜0.05).In the observation group,the length of incision was(1.65±0.29)cm,the time of opening and closing incision was(4.85±1.02)min,the hospitalization time was(3.24±0.62)d,the intraoperative blood loss was(17.88±3.53)mL,and the VAS score was(3.03±0.56)points one day after operation.The control group were(4.02±0.81)cm,(10.06±2.28)min,(7.11±1.34)d,(24.37±5.27)ml,(4.04± 0.89)points,the differences were statistically significant(P＜0.05).After treatment,The thumle-wrist sensory conduction velocity of CTS patients in the study group was(46.05±8.39)m/s,the middle finger-wrist sensory conduction velocity was(45.05±8.95)m/s,the thenar muscles-wrist motor conduction velocity was(53.94±11.47)m/s,the FIM ADL score was(34.38±7.22)points,and FMA The upper limb score was(34.23±7.25)points,and the control group was(41.86±8.22)m/s,(40.88±8.28)m/s,(49.05±10.01)m/s,(27.81±6.01)points,(41.05±9.19)points.The difference between the two groups was statistically significant(P＜0.05).The total incidence of complications was 4.00％in the observation group and 20.00％in the control group(P＜0.05).Conclusion Small incision in situ release is effective in the treatment of CTS patients,which can improve the surgical indications and nerve conduction velocity,help patients recover upper limb function,and reduce the incidence of postoperative complications.

Objective:To investigate the value of nomogram based on radiomics features of CT enterography (CTE) combined with clinical characteristics to predict secondary loss of response (SLOR) after infliximab (IFX) treatment in patients with Crohn′s disease (CD).Methods:This study was a case-control study. Clinical and imaging data of 155 patients with CD diagnosed at the First Affiliated Hospital of Anhui Medical University from March 2015 to July 2022 were retrospectively collected. The patients were divided into a training set ( n=108) and a testing set ( n=47) in the ratio of 7∶3 by stratified sampling method. All patients were treated according to the standardized protocol and were classified as SLOR (43 in the training set and 18 in the testing set) and non-SLOR (65 in the training set and 29 in the testing set) according to treatment outcome. Based on the data from the training group, independent clinical predictors of SLOR after IFX treatment were screened in the clinical data using univariate and multivariate logistic regression analysis to establish a clinical model. Intestinal phase images were selected to be outlined layer by layer along the margin of the lesion to obtain the volume of the region of interest to extract the radiomics features. The radiomics features were screened using univariate analysis and the minimum absolute shrinkage and selection operator to establish the radiomics model. Multivariate logistic regression analysis was used to build a combined clinical-radiomics model based on the screened clinical independent predictors and radiomics characters, then a nomogram was drawn. The predictive efficacy of the 3 models for SLOR after IFX treatment was assessed by receiver operating characteristic curves, and the area under the curve (AUC) was calculated. The decision curve analysis was applied to evaluate the clinical utility of the models. Results:Disease duration ( OR=1.983, 95% CI 1.966-2.000, P=0.046) and intestinal stenosis ( OR=1.246, 95% CI 1.079-1.764, P=0.015) were identified as the independent predictors of SLOR in the clinical data, and a clinical model was established. Totally 9 radiomics features were included in the radiomics model. The AUCs of clinical, radiomics, and combined models for predicting SLOR after IFX treatment in CD patients were 0.691 (95% CI 0.591-0.792), 0.896 (95% CI 0.836-0.955), and 0.910 (95% CI 0.855-0.965) in the training set, and 0.722 (95% CI 0.574-0.871), 0.866 (95% CI 0.764-0.968), and 0.889 (95% CI 0.796-0.982) in the testing set. Decision curve analysis in the testing set showed higher net clinical benefits for both the radiomics model and combined model than the clinical model, and combined model had higher net clinical benefits than the radiomics model over most threshold probability intervals. Conclusions:CTE-based radiomics model can effectively predict SLOR after IFX treatment in patients with CD, and a combined model by incorporating clinical characteristics of disease duration and intestinal stenosis can further improve the predictive efficacy.

ObjectiveTo explore the mechanism of Jiawei Wendantang in preventing and treating diabetic atherosclerosis by observing the effect of this prescription on the nuclear factor-κB / NOD-like receptor protein 3（NF-κB/NLRP3） pathway and related inflammatory cytokines in rat model of diabetic atherosclerosis. MethodFifty-four SPF-grade rats were randomized into blank， model， atorvastatin （0.9 mg·kg^-1·d^-1）， and high-， medium-， low-dose （18.2， 9.1， 4.55 g·kg^-1·d^-1， respectively） Jiawei Wendantang groups. The rats in other groups except the blank group were modeled for diabetic atherosclerosis by intraperitoneal injection of streptozotocin and feeding with a high-sugar high-fat diet， and those in the blank group were injected with an equal dose of citric acid buffer and fed with a regular diet. The drug administration lasted for 4 weeks， and the blood glucose level in the tail vein was measured every 6 days. After the last administration， the rats were anesthetized for sample collection. Enzyme-linked immunosorbent assay was employed to measure the serum levels of interleukin-18 （IL-18）， C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1）. Western blot was employed to determine the relative protein levels of NF-κB p65， NLRP3， and ICAM-1 in the abdominal aorta. Real-time quantitative polymerase chain reaction was employed to determine the mRNA levels of NLRP3 and interleukin-1β （IL-1β） in the abdominal aorta. The pathological changes in the thoracic aorta were observed by hematoxylin-eosin staining. ResultCompared with the blank group， the model group showed elevated levels of IL-18， CRP， TNF-α， and ICAM-1 in the serum and blood glucose （P<0.05， P<0.01）， up-regulated protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and up-regulated mRNA levels of NLRP3 and IL-1β （P<0.05）. Compared with model group， Jiawei Wendantang lowered the levels of IL-18， CRP， TNF-α， ICAM-1 and blood glucose （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and down-regulated the mRNA levels of NLRP3 and IL-1β （P<0.05， P<0.01）. Moreover， Jiawei Wendantang alleviated the pathological injuries in the thoracic aorta. ConclusionJiawei Wendantang may modulate the NF-κB/NLRP3 signaling pathway to reduce the release and adhesion of inflammatory cytokines and regulate the blood glucose level to treat diabetic atherosclerosis.

Background The mental health problems of employees in administrative organs and public institutions are highly valued.However,there is a lack of understanding regarding the mental health status of employees in provincial and municipal administrative organs and public institutions in Qinghai region.Objective To analyze the anxiety and depression of employees in provincial and municipal administrative organs and public institutions in Qinghai region,so as to provide references for promoting their mental health and intervening in psychological problems.Methods From October 23 to 28,2022,a total of 3 096 employees in provincial and municipal administrative organs and public institutions in Qinghai region were enrolled using stratified cluster sampling technique,and were assessed using Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS).Results A total of 1797(58.04％)employees in municipal and above administrative organs and public institutions in Qinghai region completed a valid questionnaire survey.Depressive symptoms were noted in 579(32.22％).SDS scores yielded statistical difference among the selected employees of different ethnicities,types of job positions and educational levels(F=9.074,101.488,4.477,P<0.01),and the severity of depressive symptoms also demonstrated statistical difference among the selected employees with different ethnicities,educational levels and types of job positions(H=49.196,17.028,160.848,P<0.01).Anxiety symptoms were detected in 711(39.57％)employees.SAS scores exhibited statistical difference among the employees with different genders,ages,ethnicities,educational levels,marital status and types of job positions(t=-4.571,F=6.648,3.950,5.243,12.008,22.253,P<0.01).Statistical differences were also illustrated in the severity of anxiety symptoms among the selected employees with different ages,genders,ethnicities,educational levels,marital status and types of job positions(H=24.361,-3.788,28.365,24.268,25.976,56.204,P<0.01).Conclusion About one-third of employees in municipal and above administrative organs and public institutions in Qinghai region may have symptoms of depression and anxiety.The depression symptoms are more severe among Tibetan people,those with low education levels and ordinary civil servants.The anxiety symptoms are more severe among employees aged 30 and below,those with low education levels,unmarried and those in technical positions.

ObjectiveTo explore the possible mechanism of the treatment of dry eye with liver-meridian constraint-heat syndrome by Runmu Xiaoyao Powder （润目逍遥散） by miR-146a-5p and interleukin-1 receptor-associated kinase 1/tumour necrosis factor receptor associated factor 6/nuclear factor-κB （IRAK1/TRAF6/NF-κB） signalling pathway. MethodsEighty C57BL/6J mice were randomly divided into normal group， model group， agonist group， inhibitor group， sodium hyaluronate group， and Runmu Xiaoyao Powder high-， medium-， and low-dose groups， with 10 mice in each group. Except for the normal group， the mice of dry eye with liver-meridian constraint-heat syndrome were modeled by using benzalkonium chloride solution eye drops combined with chronic pain stimulation. Beginning on the 30th day of modelling， mice in Runmu Xiaoyao Powder high-， medium-， and low-dose groups were given 29， 14.5， and 7.25 g/kg of Runmu Xiaoyao Powder respectively twice daily by gavage； mice in sodium hyaluronate group were given 5 μl of sodium hyaluronate drops twice daily； mice in the agonist group were given 2 nmol of agomir-146a-5p drops in each eye at a time， and those in the inhibitor group were given 5 nmol of antagomir-146a-5p drops in each eye， with every other day， 3 times per week； mice in the normal and model groups were gavaged with deionised water at 1 ml/（100 g·d）. The intervention was continued for 14 days in each group， and mice in each group were examined for tear secretion， tear film rupture time， corneal fluorescein staining， and irritability scores on the day following the last intervention； HE staining was used to observe the pathological conditions of the cornea and lacrimal glands in each group； corneal and lacrimal gland inflammatory factors， such as interleukin 1β （IL-1β）， tumour necrosis factor α （TNF-α）， miR-146a-5p expression， were examined； matrix metalloproteinase 3 （MMP-3） and matrix metalloproteinase 9 （MMP-9） expression in cornea， IRAK1， TRAF6， nuclear factor κB p65 （NF-κB p65） protein and mRNA expression in cornea and lacrimal gland， and phosphorylated nuclear factor κB p65 （p-NF-κB p65） protein expression were detected. ResultsCompared with the normal group， mice in the model group showed reduced tear secretion， shorter tear film rupture time， higher irritability score （P＜0.05）， and pathological examination showed staining in the centre of the cornea， obvious corneal damage， increased volume of lacrimal gland follicular cells， disordered arrangement， a large number of inflammatory cell infiltration， and increased neovascularisation； corneal and lacrimal gland tissues showed elevated expression of IL-1β and TNF-α， decreased expression of miR -146a-5p， elevated expression of IRAK1， TRAF6， NF-κB p65， p-NF-κB p65 protein and IRAK1， TRAF6， NF-κB p65 mRNA， and elevated expression of MMP-3， MMP-9 protein in the cornea （P＜0.05）. Compared with the model group， all of the above indexes were significantly improved in high-dose group of Runmu Xiaoyao Powder， while some indexes were improved in the sodium hyaluronate group and the middle- and low-dose Runmu Xiaoyao Powder groups （P＜0.05）. Compared with the model group， corneal and lacrimal IRAK1 and TRAF6 mRNA and IRAK1， TRAF6 and p-NF-κB p65 protein expression decreased in the agonist group； compared with the inhibitor group， IRAK1， TRAF6， NF-κB p65 mRNA and protein expression in the cornea and lacrimal gland in the Runmu Xiaoyao Powder groups decreased （P＜0.05）. ConclusionRunmu Xiaoyao Powder can negatively regulate the IRAK1/TRAF6/NF-κB signalling pathway in the cornea and lacrimal gland of mice with dry eye of liver-meridian constraint-heat syndrome by up-regulation of miR-146a-5p， so as to inhibit inflammatory response and reduce the damage of the ocular surface tissues， and the high doses group showed the best effect.

With various diseases ravaging internationally, the demands for recombinant adenoviral vector (Adv) vaccines have increased dramatically. To meet the demand for Adv vaccine, development of a new cell culture process is an effective strategy. Applying hyperosmotic stress in cells before virus infection could increase the yield of Adv in batch culture mode. Emerging perfusion culture can significantly increase the yield of Adv as well. Therefore, combining the hyperosmotic stress process with perfusion culture is expected to improve the yield of Adv at high cell density. In this study, a shake flask combined with a semi-perfusion culture was used as a scaled-down model for bioreactor perfusion culture. Media with osmotic pressure ranging from 300 to 405 mOsm were used to study the effect of hyperosmotic stress on cell growth and Adv production. The results showed that using a perfusion culture process with a hyperosmotic pressure medium (370 mOsm) during the cell growth phase and an isosmotic pressure medium (300 mOsm) during the virus production phase effectively increased the yield of Adv. This might be due to the increased expression of HSP70 protein during the late phases of virus replication. The Adv titer in a bioreactor with such a process reached 3.2×10¹⁰ IFU/mL, three times higher than that of the traditional perfusion culture process. More importantly, this is the first time that a strategy of combining the hyperosmotic stress process with perfusion culture is applied to the production of Adv in HEK 293 cells. It also reveals the reason why the hyperosmotic stress process increased the yield of Adv, which may facilitate the process optimization of for producing other Adv in HEK 293 cells.
Humans ; HEK293 Cells ; Genetic Vectors/genetics* ; Batch Cell Culture Techniques ; Bioreactors ; Perfusion

Primary liver cancer (hereinafter referred to as HCC) is the sixth most common type of cancer and the third leading cause of cancer-related mortality worldwide. Since patients in the early stage of HCC are typically asymptomatic and there are currently no specific detection methods for the early stage of HCC, the majority of patients are diagnosed in the late stage. Exosomes carry proteins, non-coding RNAs, such as cyclic RNAs (circRNAs), and other biological molecules. Patients with hepatocellular carcinoma have a higher concentration of serum exosomes than healthy individuals, and the circRNAs in the exosomes can reflect the source cells and real-time disease status, suggesting it has the potential to detect liver cancer early. This paper focuses on the latest progress of exosomal circRNAs and analyzes the potential value of exosomes in the early diagnosis, treatment, and progression of HCC.