Detection of 14 sulfonate esters impurities of active pharmaceutical ingredients based on GC-MS/MS and LC-MS/MS / 药学学报

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL-1 and 9-150 ng·mL-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L-1 ammonium formate (D), with a flow rate of 0.2 mL·min-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI+), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL-1, 3-100 ng·mL-1 and 0.9-30 ng·mL-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

The Uptake and Distribution Evidence of Nano- and Microplastics in vivo after a Single High Dose of Oral Exposure / 生物医学与环境科学（英文）

OBJECTIVE@#Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.@*METHODS@#Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg∙body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.@*RESULTS@#In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group ( P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h ( P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h ( P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.@*CONCLUSION@#Nanoplastics translocated rapidly to observed organs/tissues through blood circulation; however, only small amounts of MPs could penetrate the organs.

Prevalence of HCV Antibody and its Associated Factors: A Study from Sentinel Hospitals in China / 生物医学与环境科学（英文）

OBJECTIVE@#The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody in hospital patients, evaluate the epidemic trend of hepatitis C and formulate screening strategies.@*METHODS@#Patient information and HCV antibody testing results were collected from January 2017 to December 2019 in 77 HCV sentinel hospitals in China. Univariate and multivariate logistic regression was used to determine the characteristics and associations.@*RESULTS@#HCV antibody prevalence rates were distinct among patients in different departments, with a range of 0.33%-6.93%. Patients who were admitted to the liver disease-related departments (a OR = 10.76; 95% CI, 10.27-11.28), Internal Medicine (a OR = 2.87; 95% CI, 2.75-3.00), and Department of Surgery (a OR = 1.95; 95% CI, 1.87-2.04), were more likely to be tested for HCV antibody positive. HCV antibody prevalence was associated with patients aged 45 years and older (a OR = 2.74; 95% CI, 2.69-2.80), testing in infetious disease hospitals (a OR = 2.33; 95% CI, 2.26-2.40) and secondary hospitals (a OR = 1.72; 95% CI, 1.69-1.75). Patients in sentinel hospitals of the Northeast (a OR = 12.75; 95% CI, 12.40-13.11), the Central (a OR = 1.65; 95% CI, 1.61-1.70), and the West (a OR = 1.78; 95% CI, 1.73-1.83) China had higher HCV prevalence than those who were in the Eastern coastal area.@*CONCLUSION@#Those who were over 45 years old and saw doctors for liver diseases, and invasive diagnosis and treatment should be referred to HCV antibody testing.

Construction of cell factories for production of patchoulol in Saccharomyces cerevisiae / 中国中药杂志

Patchoulol is an important sesquiterpenoid in the volatile oil of Pogostemon cablin, and is also considered to be the main contributing component to the pharmacological efficacy and fragrance of P. cablin oil, which has antibacterial, antitumor, antioxidant, and other biological activities. Currently, patchoulol and its essential oil blends are in high demand worldwide, but the traditional plant extraction method has many problems such as wasting land and polluting the environment. Therefore, there is an urgent need for a new method to produce patchoulol efficiently and at low cost. To broaden the production method of patchouli and achieve the heterologous production of patchoulol in Saccharomyces cerevisiae, the patchoulol synthase(PS) gene from P. cablin was codon optimized and placed under the inducible strong promoter GAL1 to transfer into the yeast platform strain YTT-T5, thereby obtaining strain PS00 with the production of(4.0±0.3) mg·L~(-1) patchoulol. To improve the conversion rate, this study used protein fusion method to fuse SmFPS gene from Salvia miltiorrhiza with PS gene, leading to increase the yield of patchoulol to(100.9±7.4) mg·L~(-1) by 25-folds. By further optimizing the copy number of the fusion gene, the yield of patchoulol was increased by 90% to(191.1±32.7) mg·L~(-1). By optimizing the fermentation process, the strain was able to achieve a patchouli yield of 2.1 g·L~(-1) in a high-density fermentation system, which was the highest yield so far. This study provides an important basis for the green production of patchoulol.

Isobaric tags for relative and absolute quantitation quantitative proteomics research of human lens epithelial cells after ultraviolet-B irradiation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of protein expressions in human lens epithelial cells(SRA01/04)undergoing oxidative damage, hoping to provide new protein target for the pathogenesis of age-related cataract(ARC).METHODS: SRA01/04 cells were divided into experimental group and control group. In the experimental group, cells were irradiated with ultraviolet-B(UVB)for 10min to establish the model of oxidative damage, whereas cells in the control group were untreated. Protein expression profile from the two groups was sequenced by isobaric tags for relative and absolute quantitation(iTRAQ). The filtering criteria that fold change &#x0026;#x003E;1.2 and p&#x0026;#x003C;0.05 was used to determine the differentially expressed proteins(DEPs). Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)database were utilized for functional enrichment analysis of the top 50 DEPs with either up-regulated or down-regulated significance. Furthermore, Pathway commons software was used to establish the protein-protein interaction(PPI)network.RESULTS: Overall, 552 DEPs were screened out. A total of 176 DEPs were up-regulated in the experimental group compared with the control group, including HMGB1 and USP1, while 376 DEPs were down-regulated, including POLR2A and POLR2B. GO and KEGG enrichment analysis indicated that the top 50 DEPs with up-regulated or down-regulated significance were involved in various crucial biological processes and signaling pathways. PPI network revealed that oxidative damage repair(ODR)-related proteins might play a key role in UVB-induced oxidative damage.CONCLUSIONS: The expressions of multiple proteins, especially ODR-related proteins, can be altered in SRA01/04 cells via UVB irradiation. These findings may provide cellular-related insights into the pathogenesis of ARC and into proteins or pathways associated with therapeutic targets.

Diagnosis and treatment procedures and health management for patients with hereditary angioedema / 中华预防医学杂志

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

Preliminary insights into the practice of hypoallergenic home visiting program / 中华预防医学杂志

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

Diagnosis and treatment procedures and health management for patients with hereditary angioedema / 中华预防医学杂志

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

Preliminary insights into the practice of hypoallergenic home visiting program / 中华预防医学杂志

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

Effects of Anemarrhenae Rhizoma on the dissolution of 6 inorganic elements in Gypsum Fibrosum under different compatibility ratio based on grey correlation analysis and TOPSIS model / 中国药师

Objective To discuss the effect of Anemarrhenae Rhizoma with different proportions on the dissolution of 6 inorganic elements(K,Ti,Sr,Ba,Ca,Mg)in Gypsum Fibrosum under different compatibility based on grey correlation analysis and technique for order preference by similarity to an ideal solution(TOPSIS)method and to provide reference for clinical application.Methods Inductively coupled plasma mass spectrometry(ICP-MS)was established for simultaneous analysis of inorganic elements K,Ti,Sr,Ba,Ca,Mg in Gypsum Fibrosum-Anemarrhenae Rhizoma.The gray correlation ananlysis and TOPSIS method were used to comprehensively analyze the changes of six inorganic elements in Gypsum Fibrosum under different compatibility.Results The findings of the ICP-MS determination of inorganic elements in Gypsum Fibrosum-Anemarrhenae Rhizoma were good in terms of linearity,precision,repeatability and stability.The average recovery was 81.78％-104.13％,and the RSD was 2.10％-4.62％(n=6).The dissolution of six inorganic elements in Gypsum Fibrosum after compatibility with different proportions of Anemarrhena Rhizoma was significantly higher than that of Gypsum Fibrosum single decoction(P＜0.05).The dissolution scores of six inorganic elements in Gypsum Fibrosum were the highest when the compatibility proportion of Gypsum Fibrosum-Anemarrhenae Rhizoma was 30∶9.Conclusion ICP-MS is a sensitive and accurate method for determining K,Ti,Sr,Ba,Ca and Mg in Gypsum Fibrosum-Anemarrhenae Rhizoma.The best compatibility ratio of Gypsum Fibrosum-Anemarrhenae Rhizoma is 30:9,which can effectively improve the dissolution of six inorganic elements in Gypsum Fibrosum,and provide the basis for the further compatibility study of Gypsum Fibrosum and Anemarrhenae Rhizoma.

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation / 中国天然药物

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

Immunogenicity and influencing factors of hepatitis B vaccination based on different vaccination schedules among chronic kidney disease patients / 中华流行病学杂志

Objective: To explore the immunogenicity and influencing factors of hepatitis B vaccination based on different vaccination schedules among chronic kidney disease (CKD) patients. Methods: CKD patients who participated in randomized controlled trials in four hospitals in Shanxi province and completed three doses of 20 µg vaccination (at months 0, 1 and 6) and four doses of 20 µg or 60 µg vaccination (at months 0, 1, 2, and 6) were surveyed from May 2019 to July 2020.According to the ratio of 1∶1∶1, 273 CKD patients were divided into 3 groups randomly. Quantification of the anti-hepatitis B surface antigen-antibody (anti-HBs) in serum samples was performed using chemiluminescent microparticle immunoassay at months 1 and 6 after the entire course of the vaccinations. The positive rate, high-level positive rate, geometric mean concentration (GMC) of anti-HBs, and the influencing factors were analyzed by χ2 tests, analysis of variance, unconditional logistic regression analysis. Results: A total of 273 CKD patitents were participants.The positive rates in the CKD patients with four doses of 20 µg vaccination (92.96%,66/71) or 60 µg vaccination (93.15%, 68/73) were higher than that in the CKD patients with three doses of 20 µg vaccination (81.69%, 58/71) at month one after the full course of the vaccinations (P<0.05). The GMCs of anti-HBs showed similar results (2 091.11 mIU/ml and 2 441.50 mIU/ml vs. 1 675.21 mIU/ml) (P<0.05). The positive rate was higher in the CKD patients with four doses of 60 µg vaccination (94.83%,55/58) than in those with three doses of 20 µg vaccination (78.79%,52/66) (P<0.05) at month six after the full course of the vaccinations. And the GMC of anti-HBs in the patients with four doses of 60 µg vaccination (824.28 mIU/ml) was significantly higher than those in the patients with 3 or 4 doses of 20 µg vaccination (639.74 mIU/ml and 755.53 mIU/ml) (P<0.05). After controlling the confounding factors, the positive rate in the CKD patients with four doses of 60 µg vaccination were 3.19 (95%CI: 1.02-9.96) and 5.32 (95%CI: 1.27-22.19) times higher than those in the patients with three doses of 20 µg vaccination at months 1 and 6 after the full course of the vaccinations, respectively. The positive rate in CKD patients without immune suppression or hormone therapy was 3.33 (95%CI: 1.26-8.80) and 4.78 (95%CI: 1.47-15.57) times higher than those in the patients with such therapy, respectively. Conclusions: Four doses of 20 µg or 60 µg hepatitis B vaccination could improve the immunogenicity in patients with CKD. And four doses of 60 µg vaccination might play a positive role in maintaining anti-HBs in this population. The immunogenicity in the CKD patients with immune suppression or hormone therapy was poor.

Chemosensitizing effect and mechanism of imperatorin on the anti-tumor activity of doxorubicin in tumor cells and transplantation tumor model

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/ DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

Co-amorphous technology to improve dissolution and physical stability of silybin / 中国中药杂志

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.

Discussion on the indications and timing of targeted therapy and immunotherapy before and after liver transplantation for hepatocellular carcinoma / 器官移植

Liver transplantation is one of the main treatments of early hepatocellular carcinoma (HCC). The recurrence of HCC after liver transplantation severely affects the long-term survival rate of the recipients. Targeted therapy and immunotherapy play a critical role in HCC downstaging, preventing disease progression, reducing recurrence rate, prolonging the survival and improving the quality of life. However, no consensus has been reached on the application of targeted therapy and immunotherapy in recipients undergoing liver transplantation for HCC, including indications, timing and dosage. In this article, clinical research progresses on the indications and timing of targeted therapy and immunotherapy before and after liver transplantation for HCC were reviewed, aiming to provide reference for prolonging the survival of recipients after liver transplantation for HCC.

Circular RNA_0003028 targeting microRNA-498 regulating the effects of suppressor with morphogenesis effect on genitalia-l/p53 signaling pathway on liver cancer cell line Huh7 / 解剖学报

Objective To investigate the effects and molecular mechanism of circular RNA (circ) _0003028 on proliferation, migration and invasion of human liver cancer cells. Methods Liver cancer cell line Huh7 were divided into small interfering RNA(si)-NC group, si-circ_0003028 group, microRNA(miR) -NC group, miR-498 mimics group, si-circ _0003028+anti-miR-NC group and si-circ_0003028+anti-miR-498 group. Real-time PCR was used to detect the expression levels of circ _ 0003028 and miR-498 in liver cancer tissues and cells of each groups. MTT was used to detect cell proliferation. Transwell was used to detect cell migration and invasion. Western blotting was used to detect protein expression. Dual luciferase reporter experiment was used to detect the target regulation relationship between circ_0003028 and miR-498. Results The expression level of circ_0003028(0.98±0.02 vs 1. 36±0. 01) increased and the expression level of miR-498(0. 98±0. 02 vs 0. 63±0. 02) decreased in liver cancer tissues (P<0. 05). After inhibiting the expression of circ_0003028 or overexpression of miR-498- the expression levels of Ki-67(0. 85±0. 02 vs 0. 41±0. 02 or 0. 95±0. 11 vs 0. 37±0. 02)- matrix metalloprotein(MMP)-2(0. 71±0. 02 vs 0. 43±0. 03 or 0. 83±0. 02 vs 0. 41±0. 03)- and MMP-9 (0. 74±0. 02 vs 0. 37±0. 02 or 0. 78±0. 02 vs 0. 39±0. 02) proteins in Huh7 cells decreased- and cell viability(1. 53± 0. 03 vs 1. 05±0. 02 or 1. 68±0. 02 vs 1. 11±0. 02) decreased- the number of migration(111. 40±2. 12 vs 77. 22±2. 38 or 108. 90±2. 30 vs 78. 44 ± 1. 46) and invasion ( 87. 89 ± 2. 18 vs 49. 78 ± 1. 98 or 80. 22 ± 1. 79 vs 38. 22 ± 1. 52) cells decreased- and the protein expression levels of suppressor with morphogenesis effect on genitalia-1( SMG-1) (0. 76±0. 02 vs 1. 39±0. 02 or 0. 79±0. 02 vs 1. 39±0. 02)- p53(0. 77±0. 02 vs 1. 24±0. 03 or 0. 82±0. 03 vs 1. 45±0. 03)- and p53- ser15(0. 78±0. 03 vs 1. 50±0. 02 or 0. 82±0. 02 vs 1. 49±0. 04) increased (P<0. 05). circ_0003028 targeted regulation of miR-498- and silencing miR-498 reversed the effects of inhibiting the expression of circ_0003028 on the proliferation- migration and invasion of Huh7 cells. Conclusion Inhibiting the expression of circ_0003028 can inhibit the proliferation- migration and invasion of liver cancer cells by targeting miR-498 to affect the SMG-1/ p53 signaling pathway.

Prevalence, Risk Factors, and Psychological Effects of Overactive Bladder in Chinese University Students / 대한배뇨장애요실금학회지

Purpose@#The purpose of this study was to investigate the prevalence and risk factors of overactive bladder (OAB) in young adults and to explore the influence of OAB on mental health. @*Methods@#Between October 2019 and January 2020, 14,010 anonymous questionnaires were distributed to freshmen at 2 universities in Henan, China. The students came from all over the country. The questionnaire included general items and information necessary to calculate the overactive bladder symptom score, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) score, Self-Esteem Scale (SES) score, and Self-Rating Depression Scale (SDS) score. The relationships between the prevalence of OAB and its risk factors were evaluated. @*Results@#The overall prevalence of OAB was 6.0%, with 4.3% of participants characterized as having dry OAB and 1.7% as having wet OAB. The prevalence of mild OAB was 5.5%, and that of moderate OAB was 0.5%; no severe OAB was observed. Higher prevalence rates of OAB were found among women, respondents with constipation, and respondents with primary nocturnal enuresis (PNE) (P <0.05). Compared to healthy controls, the OAB group exhibited a higher mean SDS score (52.12±8.986 vs. 47.71±9.399, P<0.001) and mean PSQI score (5.28±2.486 vs. 4.27±2.431, P<0.001), but a lower mean SES score (27.78±3.599 vs. 29.57±4.109, P<0.001). @*Conclusions@#OAB significantly affects the mental health of young adults. Female sex, constipation, and PNE are risk factors for OAB.

Otological and hearing characteristics in children with Turner syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the otological and hearing characteristics in children with Turner syndrome (TS), to determine risk factors of hearing loss, and to discuss algorithms for future surveillance. Methods: The clinical data of otolaryngology in children with TS from January 2018 to April 2020 were reviewed retrospectively. A total of 46 female children with TS, aged from 5 to 18 years were enrolled. Karyotypes included 17 cases (37.0%) of monosomy, 16 cases (34.7%) of mosaicism, and 13 cases (28.3%) of abnormal X chromosome structures. The otoscopic characteristics, audiological performance, and otologic diagnoses were evaluated. Multivariate logistic regression and Mann-Whitney U test were used for statistical analysis. Results: The most common otologic comorbidity was otitis media with effusion (OME), including 20 cases (43.5%) with 33 ears (35.9%). 14 cases (30.4%) were diagnosed with hearing loss. The regression analysis revealed that the age (OR=1.345, 95%CI: 1.072-1.760) and comorbidity of OME (OR=9.460, 95%CI: 2.065-60.350) were risk factors associated with hearing loss. In TS with OME, when compared with the mean air conduction threshold, the hearing loss of the group with pars flaccida retractions was significantly higher ((24.3±13.8) dB HL vs. (14.4±4.2) dB HL, U=59.500, P=0.008) than that of the group with none retractions. Conclusion: OME and hearing loss are common in children with TS. As age increases or suffers from OME, the risk of hearing loss increases.

Thirty years' changes of the strategy of lateral lymph node dissection in low rectal cancer: treatment experience and prognostic analysis of 289 cases in one single center / 中华胃肠外科杂志

Objective: The surgical indications, resection extent and management principle of lateral lymph node dissection (LLND) in lower rectal cancer have been controversial between Eastern and Western countries. This study aims to provide a theoretical basis for the rational implementation of LLND by reviewing the changes of LLND strategy over the past 30 years in a single-center, and analyzing prognostic factors for the survival outcomes of patients with lateral lymph node metastasis (LLNM). Methods: A retrospective observational study was performed. Clinical data of 289 patients with rectal cancer who received LLND at the Department of General Surgery of Peking University First Hospital from 1990 to 2019 were collected. Patients were divided into three groups based on decades. There were 89 cases in 1990-1999 group, 92 cases in the 2000-2009 group, and 108 cases in the 2010-2019 group. Data analyzed: (1) patient baseline data; (2) surgery and postoperative recovery; (3) lateral lymph node dissection; (4) postoperative survival and prognosis of patients with positive lateral lymph nodes. The surgical methods and pathological results of LLND were compared between groups, and the prognostic risk factors of patients with LLNM were analyzed. Results: A total of 289 patients underwent radical resection with LLND' accounting for 6.3% of the 4542 patients with rectal cancer during the same period in our hospital. Except decade-by-decade increase in tumors with distance from anal verge ≤ 7 cm, the proportion of ulcerated tumors, and the proportion of neoadjuvant radiochemotherapy, the differences in other baseline data were not statistically significant among 3 decade groups (all P>0.05). The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2490), χ(2)=40.159, P<0.001]. The proportion of laparoscopic surgery and unilateral LLND increased, while the mean operative time, intraoperative blood loss, surgical complications above grade III and postoperative hospital stay decreased decade by decade. These 289 patients completed a total of 483 lateral dissections, including 95 cases of the unilateral dissection and 194 cases of the bilateral dissection. The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2510), P<0.001]. The median number of dissected lymph nodes in the internal iliac artery and obturator regions increased (2 vs. 3 vs. 3, P<0.001), but those in the common iliac and external iliac regions decreased significantly (4 vs. 3 vs. 2, P=0.014). A total of 71 patients with LLNM were identified. The rate of LLNM in the 2010-2019 group was significantly higher than that in the previous two groups [37.0% (40/108) vs. 16.9% (15/89) vs. 17.4% (16/92), P=0.001]. The patients with LLNM showed a poorer overall survival (OS) and disease-free survival (DFS) compared with negative lateral lymph nodes (P<0.001). There were statistically significant differences in 5-year OS rate (30.9% vs. 27.2% vs. 0, P=0.028) and 5-year DFS rate (28.3% vs. 16.0% vs. 0, P=0.038) among patients with only internal iliac lymph node metastasis, patients with only obturator lymph node metastasis, and patients with external iliac or common iliac lymph node metastasis. Multivariate analysis of prognostic factors showed that external iliac or common iliac lymph node metastasis was an independent risk factor for OS (HR=1.649, 95%CI: 1.087-2.501) and DFS (HR=1.714, 95%CI: 1.173-2.504) in patients with LLNM (all P<0.05) . The OS and DFS were not significant different in patients with LLNM among 3 decade groups. Conclusions: In the past decade, the proportion of LLND in rectal cancer has decreased significantly. However, LLNM rate has been significantly increased due to preoperative imaging assessments focusing on suspicious LLNM without compromising the survival. Internal iliac artery and obturator lymph nodes can be regarded as regional lymph nodes with a satisfactory prognosis after LLND. For suspected external iliac or common iliac lymph node metastasis, the significance of LLND remains to be further evaluated.

Clinical analysis of 554 patients with colorectal diverticulosis / 中华胃肠外科杂志

Objective: Most patients with asymptomatic colorectal diverticulosis are easily overlooked. However, some of diverticulosis become diverticulitis, bleeding and even perforation, which cause extensive harm to patients. The purpose of this study is to analyze the incidence, clinical features, diagnosis and treatment of colorectal diverticulosis in order to improve the clinical understanding of diverticulosis and its related complications. Methods: A descriptive cohort study was carried out. Clinical data of 554 patients with colorectal diverticulosis confirmed by CT, colonoscopy, digestive tract radiography or operation in Peking University First Hospital from January 2009 to June 2019 were retrospectively analyzed. Patients with malignant tumors, autoimmune diseases, long term use of immunosuppressive drugs, chronic liver diseases and renal diseases, and mental disorders were excluded. The analysis parameters included gender, onset age, clinical symptoms, location of diverticulitis, treatment and prognosis. According to the criteria established by the World Society of Emergency Surgery (WSES), acute diverticulitis was divided into 5 stages based on the extension of the infectious process. Stage 0 was simple diverticulitis and stage 1-4 was complicated diverticulitis. Results: Among the 554 patients with colorectal diverticulosis, 358 (64.6%) were males, the median onset age was 63 years; 191 patients (34.5%) had various digestive symptoms, of whom 113 (20.4%) had chronic constipation and abdominal distension, 78 (14.1%) had chronic diarrhea and abdominal pain; the other 363 patients had no obvious abdominal symptoms. Four hundred and six patients were found by colonoscopy and 465 patients were found by CT. Twenty-five patients were diagnosed by lower gastrointestinal tract radiography and 3 were confirmed during operation. There were 339 patients with multiple diverticula (61.2%) and 215 patients with single diverticulum (38.8%). 76.5% (424/554) of diverticula were located in colon, 37.0% (205/554) in ascending colon, 21.3% (118/554) in multiple sites, and 2.2% (12/554) in rectum. The median diameter of diverticulum was 7 mm, and 78 cases (14.1%) was ≥30 mm. Forty-nine patients (8.8%) developed acute diverticulitis, including 13 patients with simple diverticulitis and 36 patients with complicated diverticulitis. Among 36 patients with complicated diverticulitis, 29 (80.6%) were males, 27 (75.0%) had recurrent abdominal pain and fever before onset; diverticula of 25 cases were located in sigmoid colon; 11 cases in ascending colon. Nine cases developed sigmoid colon perforation and 8 cases developed vesicocolonic fistula, and these 17 patients underwent surgical treatment. The other 19 cases with complicated diverticulitis developed gastrointestinal bleeding, of whom 18 cases were male, 11 cases were located in ascending colon; 13 cases were healed after conservative treatment, 4 cases received endoscopic hemostatic intervention, and 2 cases underwent surgery. Conclusions: Colorectal diverticulosis is more common in male patients, and CT and colonoscopy are main diagnostic methods. The symptoms of complicated colonic diverticulitis are related to the location of diverticulum. In addition to symptomatic treatment, surgical procedures are the most important treatments.