Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Objective To investigate whether Angelica Sinensis and Astragalus capsules(AAC)regulates myocardial autophagy in heart failure rats via the phosphatidylinositol 3 kinase(PI3K)/protein kinase(Akt)/mammalian target of sirolimus(mTOR)signaling pathway.Methods A rat model of heart failure was constructed by intraperitoneal 2.5 mg·kg-1 doxorubicin,and another 8 rats served as the control group.The modeling rats were randomly divided into model group,control group and experimental-L,-M,-H groups.Control group was given 30 mg·kg-1 3-methyladenine by intraperitoneal injection;experimental-L,-M,-H groups were given 150,300 and 450 mg·kg-1 AAC by gavage,respectively;blank and model groups were given the same quantity of sterile distilled water.Six groups were administered once daily for 6 weeks.The cardiac function was measured by ultrasound,and the expression levels of PI3K,Akt,mTOR,sequestosome 1(P62)and microtubule-associated light chain protein 3-Ⅱ/Ⅰ(LC3 Ⅱ/Ⅰ)in myocardial tissue were measured by Western blot.Results In the blank,model,control and experimental-H groups,the left ventricular ejection fraction values were(85.00±3.63)％,(56.75±4.83)％,(75.63±3.70)％and(72.75±4.23)％;the relative expression levels of PI3K were 1.00±0,0.28±0.05,0.64±0.08 and 0.74±0.16;phosphorylated Akt/Akt were 1.00±0,0.49±0.06,0.90±0.16 and 0.95±0.10;phosphorylated mTOR/mTOR values were 1.00±0,0.42±0.09,0.73±0.13 and 0.83±0.08;the relative expression levels of P62 proteins were 1.00±0,0.24±0.12,0.57±0.09 and 0.96±0.10;the relative expression levels of LC3 Ⅱ/Ⅰ proteins were 1.00±0,4.31±0.75,2.20±0.76 and 1.59±0.24,respectively.Compared to the model group,statistical significant were identified in the experimental-H and control groups(all P＜0.05).Conclusion AAC can regulate PI3K/Akt/mTOR pathway,inhibit myocardial autophagy and improve cardiac function in rats with heart failure.

Objective:This study aims to evaluate the clinical efficacy and safety of Dibai Yijing Formula(DYF)in the treat-ment of male infertility with essence deficiency in the kidney and damp-heat in the essence chamber(Abbreviation:kidney deficiency and damp-heat type).Methods:This study employed a randomized,controlled clinical trial design,recruiting 72 male patients with infertility due to kidney deficiency and damp-heat type.Patients were randomly assigned to an treatment group(36 patients)and a control group(36 patients)using a random number table.The control group received oral Clomiphene Citrate Capsules(50 mg,twice daily),while the treatment group received oral DYF(one dose daily,200 ml each time,30 minutes after breakfast and dinner).Both groups underwent a 12-week treatment period.After treatment,sperm concentration(SC),percentage of progressively motile sperms(PR),total sperm motility[PR+percentage of non-progressively motile sperms(NP)],and semen volume(SV)were compared between the two groups before and after treatment.Additionally,the total score of Traditional Chinese Medicine(TCM)syndrome score and sperm DNA fragmentation index(DFI)and pregnancy outcomes of the patients'spouses were compared between the two groups.Results:Three patients dropped out from the treatment group and four from the control group.There were no statistically sig-nificant differences in semen parameters between the two groups(P＞0.05).After treatment,the patients in the treatment group showed significant difference in the percentage of SC([19.42±5.30]x 106/ml vs[10.75±2.41]x 106/ml),PR([27.72±6.62]％vs[20.04±4.10]％),PR+NP([49.86±10.68]％vs(33.74±5.58)％],DFI([12.33±3.43]％vs[15.06±3.98]％)and TCM symtom score([7.45±1.82]vs[13.85±1.91]),and the difference was statistically significant(P＜0.05).The patients in the control group showed significant difference in the percentage of SC([19.56±5.24]× 106/ml vs[11.31±2.08]× 106/ml)and TCM symptom score([12.81±1.86]vs[14.06±1.64]).But no significant changes were observed in the PR([21.75±5.93]％vs[20.05±4.67]％),PR+NP([34.23±7.15]％vs[32.35±4.09]％),SV([3.19±1.08]ml vs[3.12±1.13]ml),and DFI([15.11±4.76]％vs[15.51±4.35]％)were not statistically significant(P＞0.05).Improve-ments in PR,PR+NP,TCM symptom score and DFI in the treatment group were better than those in the control group after treatment(P＜0.05);the differences in SC and SV and spousal pregnancy in the treatment group were not statistically significant compared with those in the control group(P＞0.05).No serious adverse events occurred in both groups during the treatment period.Conclusion:The treatment of male infertility with DYF is effective and safe.

OBJECTIVE: Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness. METHODS: A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected. RESULTS: Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3β/β-catenin signaling pathway. Additionally, the desmin⁺/CD31⁺ ratio, rather than the number of CD31⁺ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group. CONCLUSION Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3β/β-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway. J Integr Med. 2023; 21(2): 184-193.
Humans ; Animals ; Mice ; Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; Mice, Nude ; Glycogen Synthase Kinase 3 beta/genetics* ; beta Catenin/therapeutic use* ; Liver Neoplasms/drug therapy* ; Desmin/therapeutic use* ; Ki-67 Antigen ; Cell Line, Tumor ; Hypoxia ; RNA, Messenger/therapeutic use* ; Cell Proliferation

Rhein is an anthraquinone compound extracted from rhubarb, aloe vera, Polygonum multiflorum. In this study, we screened the potential targets of rhein through protein chip technology and investigated the underlying mechanism of its inhibition of colorectal cancer. Colony formation assay and scratch assay were used to examine the effect of rhein on the proliferation and migration abilities of HCT116 cell; KEGG and protein interaction analyses of rhein specific binding proteins by screening rhein binding proteins using protein chip; qRT-PCR and Western blot assays were used to determine the effect of rhein on the expression levels of BCL-2-associated X protein (BAX), B-cell lymphoma-2 (BCL-2) and argininosuccinate synthetase 1 (ASS1) in HCT116 cell. The antitumor effect of rhein was verified by azoxymethane combined with dextran sodium sulfate (AOM/DSS) induced colorectal cancer model. Experimental animal procedures were performed in accordance with animal welfare and the standards of the Laboratory Animal Ethics Committee of South China Agricultural University, with approval from the ethics committee. In vivo and in vitro results indicate that rhein specific binding proteins are mainly involved in amino acid anabolism, especially the arginine anabolic signaling pathway. Rhein inhibited the proliferation and migration of HCT116 cell in a concentration-dependent manner. Treated with rhein for 24 h significantly enhanced the expression of BAX and ASS1 in HCT116 cells, as well as the level of nitric oxide (NO) metabolism. In a mouse model of colorectal cancer, rhein significantly alleviated AOM/DSS induced weight loss and reduced fecal occult blood score. Meanwhile, rhein enhanced BAX and ASS1 expression in colon tumor tissue, as well as increased arginine and NO in serum. IHC and HE stain indicated that rhein alleviated Ki67 expression and macrophage infiltration in the colonic tissue of mice with AOM/DSS and delayed tumor formation. In conclusion, rhein can exert antitumor activity by regulating arginine and NO metabolism through ASS1.

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

This report presented the endemic status of schistosomiasis in the People’s Republic of China at a national level in 2020, and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance sites. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis in China, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2020. A total of 450 counties (cites, districts) were found to be endemic for schistosomiasis in China, with 28 376 endemic villages covering 71 370 400 people at risk of infections. Among the 450 endemic counties (cities, districts), 74.89% (337/450), 21.87% (98/450) and 3.33% (15/450) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. By the end of 2020, 29 517 cases with advanced schistosomiasis were documented in China. In 2020, 11 117 655 individuals received inquiry examinations and 1 798 580 were positive; 5 263 082 individuals received serological tests and 83 179 were sero-positive. A total of 273 712 individuals received stool examinations and 3 were positive, including one case of acute schistosomiasis. In 2020, snail survey was performed in 19 733 endemic villages in China and Oncomelania snails were found in 7 309 villages, accounting for 37.04% of all surveyed villages, with 15 villages identified with emerging snail habitats. Snail survey covered an area of 736 984.13 hm² and 206 125.22 hm² snail habitats were found, including 1 174.67 hm² emerging snail habitats and 1.96 hm² habitats with infected snails. In 2020, 544 424 bovines were raised in the schistosomiasis-endemic areas of China, and 147 887 received serological examinations, with 326 positives detected, while 130 673 bovines received stool examinations, with no positives identified. In 2020, there were 19 214 patients with schistosomiasis receiving praziquantel chemotherapy, and 964 103 person-time individuals and 266 280 herd-time bovines were given expanded chemotherapy. In 2020, molluscicide treatment was performed in 136 141.92 hm² snail habitats, and the actual area of chemical treatment was 71 980.22 hm², while environmental improvements were performed in snail habitats covering an area of 1 464.03 hm². Data from the national schistosomiasis surveillance sites of China showed that the mean prevalence of Schistosoma japonicum infections were both zero in humans and bovines in 2020, and no S. japonicum infection was detected in snails. The results demonstrate that the overall endemic status of schistosomiasis remains at a low level in China and the goal of the National Thirteenth Five-Year Plan for Schistosomiasis Control was achieved as scheduled; however, the endemic situation of schistosomiasis rebounded in local areas. Precision schistosomiasis control and intensified monitoring of the endemic situation and transmission risk of schistosomiasis are required to be performed to facilitate the progress towards elimination of schistosomiasis steadily.

In this study, the effect of benzo[α]pyrene (BaP) on chaperone-mediated autophagy (CMA) in a simulated hypoxia environment was observed and the relationship to heat shock protein 90 (HSP90) was clarified. With HSP90 inhibitor geldanamycin (GA) and HSP90α silenced, the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), HSP90, heat shock cognate protein 70 (HSC70), and lysosomal associated protein 2A (LAMP-2A) of A549 cells on hypoxic environment by BaP were tested. Alkaline comet experiment, immunofluorescence γ-H2AX focus experiment, quantitative real-time PCR (qPCR), and Western blot analyses were used to clarify the relationship between the DNA damage of different concentrations of BaP in A549 cells and the mRNA and protein expression of CMA-related factors. The results show that hypoxia can promote the expression of mRNA and protein of CMA-related factors in A549 cells. This study found that BaP has an inhibitory effect on CMA under the hypoxic environment. The inhibition or silencing of HSP90 will enhance the inhibitory effect of BaP on CMA. In a normoxic environment, BaP causes DNA damage and promotes CMA.

This report presented the endemic status of schistosomiasis in the People’s Republic of China at a national level in 2019, and analyzed the data collected from the national schistosomiasis prevention and control system and 455 national schistosomiasis surveillance sites. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis in China, Shanghai, Zhejiang, Fujian, Guangdong and Guangxi continued to consolidate the achievements of schistosomiasis elimination, Sichuan Province achieved transmission interruption, Jiangsu newly achieved the standard of transmission interruption and 5 provinces of Yunnan, Hubei, Anhui, Jiangxi and Hunan maintained transmission control by the end of 2019. There were 450 endemic counties (cities, districts) endemic for schistosomiasis, including 28 500 endemic villages covering 70 667 800 people at risk of infections. Among the 450 endemic counties (citis, districts), 66.89% (301/450), 28.44% (128/450) and 4.67% (21/450) kept the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. By the end of 2019, a total of 30 170 advanced schistosomiasis cases were documented in China. In 2019, a total of 12 090 712 individuals received inquiry examinations and 1 740 764 were positive; 5 158 369 individuals received serological tests and 89 753 were seropositive. A total of 327 475 individuals received stool examinations and 5 were positive, including one case of acute schistosomiasis. In 2019, snail survey was performed in 19 726 endemic villages in China and Oncomelania snails were found in 7 322 villages, accounting for 37.12% of all surveyed villages, with 6 villages with emerging snail habitats. Snail survey covered an area of 585 286.24 hm² and 174 270.42 hm² snail habitats were found, including emerging snail habitats of 64.20 hm²; however, no infected snails were identified. In 2019, a total of 605 965 bovines were raised in the schistosomiasis endemic areas of China, and 183 313 received serological examinations, with 1 176 positives detected, while 134 978 bovines received stool examinations, with 7 positives identified. In 2019, there were 28 557 patients with schistosomiasis receiving praziquantel chemotherapy, and expanded chemotherapy was given to 1 008 083 person-times; there were 7 bovines with schistosomiasis receiving praziquantel chemotherapy, and 296 053 herd-times expanded chemotherapy was given to bovines. In 2019, snail habitats at an area of 128 754.26 hm² were given chemical treatment, and the actual area of chemical treatment was 69 605.55 hm², while environmental improvements were performed in snail habitats covering an area of 2 847.00 hm². Data from the 455 national schistosomiasis surveillance sites of China showed that the mean Schistosoma japonicum infection rates were both zero in humans and bovines in 2019, and no infected snails were found. The results demonstrate that the overall endemic situation of schistosomiasis remains at a lower infection level in China; however, there is still a risk of schistosomiasis transmission. To achieve the target set in the National Thirteenth Five-Year Plan for Schistosomiasis Control and consolidate the achievements of schistosomiasis control, precision control on schistosomiasis still needs to be reinforced in China.

The relationship between areca nut as a primary carcinogen and oral cancer has been widely concerned. Areca can change the levels of reactive oxygen species (ROS) and autophagy in cells, and the levels of ROS and autophagy are closely related to the occurrence and development of tumors. This paper reviewed the relationships among areca nut, intracellular ROS, and autophagy.
Areca ; Autophagy ; Humans ; Mouth Neoplasms ; Nuts ; Oral Submucous Fibrosis ; Reactive Oxygen Species