Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

Associations between indoor volatile organic compounds and nocturnal heart rate variability of young female adults: A panel study / 北京大学学报(医学版)

OBJECTIVE@#To investigate the association between short-term exposure to indoor total volatile organic compounds (TVOC) and nocturnal heart rate variability (HRV) among young female adults.@*METHODS@#This panel study recruited 50 young females from one university in Beijing, China from December 2021 to April 2022. All the participants underwent two sequential visits. During each visit, real time indoor TVOC concentration was monitored using an indoor air quality detector. The real time levels of indoor temperature, relative humidity, noise, carbon dioxide and fine particulate matter were monitored using a temperature and humidity meter, a noise meter, a carbon dioxide meter and a particulate counter, respectively. HRV parameters were measured using a 12-lead Holter. Mixed-effects models were used to evaluate the association between the TVOC and HRV parameters and establish the exposure-response relationships, and two-pollutant models were applied to examine the robustness of the results.@*RESULTS@#The mean age of the 50 female subjects was (22.5±2.3) years, and the mean body mass index was (20.4±1.9) kg/m2. During this study, the median (interquartile range) of indoor TVOC concentrations was 0.069 (0.046) mg/m3, the median (interquartile range) of indoor temperature, relative humidity, carbon dioxide concentration, noise level and fine particulate matter concentration were 24.3 (2.7) ℃, 38.5% (15.0%), 0.1% (0.1%), 52.7 (5.8) dB(A) and 10.3 (21.5) μg/m3, respectively. Short-term exposure to indoor TVOC was associated with significant changes in time-domain and frequency-domain HRV parameters, and the exposure metric for most HRV parameters with the most significant changes was 1 h-moving average. Along with a 0.01 mg/m3 increment in 1 h-moving average concentration of indoor TVOC, this study observed decreases of 1.89% (95%CI: -2.28%, -1.50%) in standard deviation of all normal to normal intervals (SDNN), 1.92% (95%CI: -2.32%, -1.51%) in standard deviation of average normal to normal intervals (SDANN), 0.64% (95%CI: -1.13%, -0.14%) in percentage of adjacent NN intervals differing by more than 50 ms (pNN50), 3.52% (95%CI: -4.30%, -2.74%) in total power (TP), 5.01% (95%CI: -6.21%, -3.79%) in very low frequency (VLF) power, and 4.36% (95%CI: -5.16%, -3.55%) in low frequency (LF) power. The exposure-response curves showed that indoor TVOC was negatively correlated with SDNN, SDANN, TP, and VLF when the concentration exceeded 0.1 mg/m3. The two-pollutant models indicated that the results were generally robust after controlling indoor noise and fine particulate matter.@*CONCLUSION@#Short-term exposure to indoor TVOC was associated with significant negative changes in nocturnal HRV of young women. This study provides an important scientific basis for relevant prevention and control measures.

ALDH5A1 Downregulation Promotes Tumor Metastasis and Contributes to Poor Prognosis in Ovarian Cancer / 肿瘤防治研究

Objective To investigate the expression level and clinical significance of ALDH5A1 in ovarian cancer (OC) tissues, as well as to explore the possible mechanism associated with the invasion and migration of OC cells. Methods We initially compared ALDH5A1 expression in metastatic tissues and the primary site of OC based on the GEO database. Then, wound-healing and Transwell assays were utilized to determine the biological role of OC cells transfected with ALDH5A1 siRNA. To unravel the potential mechanism of ALDH5A1 meditating the metastasis of OC, the coexpression profile of ALDH5A1 in OC cell lines and OC patients were generated using cBioPortal. Moreover, the TCGA and GEO databases were used to analyze the relationship between ALDH5A1 expression and the prognosis of OC patients. The HPA database was further used to confirm the relative expression of ALDH5A1 and MMPs in OC patients. Results ALDH5A1 expression was downregulated in metastatic tissues compared with the primary site of OC, and ALDH5A1 knockdown promoted the malignant behavior of OC cells. Additionally, the coexpression profile of ALDH5A1 was significantly enriched in the extracellular matrix (ECM) organization pathway. Western blot assay further confirmed that the expression of MMP, which played an important role in the ECM pathway, was negatively correlated with ALDH5A1 expression in OC. These results indicated that ALDH5A1 may participate in the metastasis and invasion of OC via the ECM organization pathway. Finally, KM survival plots revealed that the survival rates of OC patients with lower ALDH5A1 expression were obviously lower. Conclusion ALDH5A1 downregulation may promote the tumor metastasis and contribute to poor prognosis in OC.

Berberine Inhibits Atherosclerosis by Regulating Lipophagy Via Targeting Wnt5a/NPC1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the regulatory effect and molecular mechanism of berberine （BBR） on lipophagy in the prevention and treatment of atherosclerotic （AS） lesions in mice. MethodFifty apolipoprotein E-knockout （ApoE-/-） mice were randomly divided into an AS model group， an atorvastatin group （5 mg·kg-1）， and low-， medium-， and high-dose BBR groups （2.5， 5， 10 mg·kg-1）. Ten C57BL/6J mice were assigned to the control group. After 12 weeks， hematoxylin-eosin （HE） and oil red O staining were performed to assess the histopathological changes of AS plaques in the aorta. Biochemical analysis was used to measure serum lipid levels， and enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory cytokines interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， oxidative stress marker reactive oxygen species （ROS）， and serum lipophagy marker Beclin1 and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）. The xanthine oxidase method was used to measure serum superoxide dismutase （SOD） activity. Immunohistochemistry （IHC） was used to detect the distribution of wingless-type MMTV integration site family member 5a （Wnt5a） and Nieman Pick type C1 （NPC1） in the aorta， and Western blot was used to determine the protein expression of Wnt5a and NPC1 in the aorta. ResultCompared with the control group， the AS model group showed significant AS plaque formation， significantly elevated levels of serum total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， IL-6， TNF-α， and ROS， aortic Wnt5a distribution and protein expression （P<0.01）， and significantly reduced levels of serum high-density lipoprotein cholesterol （HDL-C）， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.01）. Compared with the AS model group， the atorvastatin group， and high- and medium-dose BBR groups showed a significant reduction in AS plaque area （P<0.05， P<0.01）， significantly decreased levels of serum TC， TG， LDL-C， IL-6， TNF-α， ROS， and aortic Wnt5a distribution and protein expression （P<0.05， P<0.01）， and significantly increased levels of serum HDL-C， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.05， P<0.01）. There was no statistically significant difference in the above indicators between the atorvastatin group and the medium-dose BBR group. ConclusionBBR can competitively bind to Wnt5a to activate NPC1 expression， upregulate lipophagy levels， reduce blood lipids， and inhibit the release of inflammatory mediators and oxidative stress damage， thereby exerting a preventive and therapeutic effect on AS.

Severe COVID-19 complicated with mild encephalitis/encephalopathy with reversible splenial lesion of the corpus callosum: a case report / 中华神经科杂志

Since the global COVID-19 pandemic, SARS-CoV-2 infection, which causes COVID-19, has been associated with a range of diseases whose atypical manifestations have been increasingly reported. The mild encephalitis or encephalopathy associated with reversible corpus callosum lesions or mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare clinical and radiographic syndrome. At present, the pathogenesis of MERS caused by COVID-19 is still unclear, and its pathogenesis may include hypoxic damage, inflammatory response, immune disorders, changes in osmotic pressure, excitatory amino acid toxicity, oxidative stress and functional abnormalities of renin-angiotensin system. This paper reports a case of severe COVID-19 complicated with MERS, and discusses the pathogenesis from a pathophysiological point of view.

Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway / 中西医结合学报

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.

Analysis on Medication Regularity of Traditional Chinese Medicine in Treatment of Intermediate and Advanced Non-small Cell Lung Cancer Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo explore medication regularity of traditional Chinese medicine （TCM） in the treatment of non-small cell lung cancer （NSCLC） and thereby to lay a theoretical basis for clinical medication and drug development. MethodArticles on clinical treatment of intermediate and advanced NSCLC with TCM in the past 40 years were retrieved from CNKI， which were taken the data source. Then the articles were screened to establish a formula database， followed by frequency statistics， association rule analysis， cluster analysis， factor analysis， and complex network construction. ResultA total of 307 eligible articles were screened out， involving 483 formulas. The common syndrome of intermediate and advanced NSCLC was the deficiency of both Qi and Yin， with the common syndrome elements of Qi deficiency， Yin deficiency， phlegm， blood stasis， pathogenic heat （fire）， toxin， and pathogenic dampness. The frequently used medicinals mainly had the functions of tonifying deficiency， clearing heat， resolving phlegm and relieving cough and dyspnea， promoting urination and draining dampness， and activating blood and resolving stasis. The high-frequency medicinals were Astragali Radix， Glycyrrhizae Radix et Rhizome， Ophiopogonis Radix， Fritillariae Thunbergii Bulbus， and Poria， which were mainly cold， bitter， sweet， and pungent， with tropism at lung， spleen， and stomach. The association rule analysis yielded 17 rules with strong association. Ten common factors were extracted from the factor analysis， and cluster analysis classified the medicinals into 5 groups. Complex network analysis suggested that the core formula was modified Liujunzi Tang and Yiqi Yangyin Jiedu prescription. ConclusionThe treatment principle for intermediate and advanced NSCLC is replenishing Qi and nourishing Yin， invigorating spleen and resolving phlegm， clearing heat and detoxifying， promoting blood circulation and removing blood stasis. The core combinations new prescription discovered by data mining are of important guiding significance， but they should be further verified in clinical practice and by experiments based on the theory of TCM.

Value of prostate biopsy guided by transrectal real-time ultrasonic elastography combined with peak strain index in the diagnosis of prostate cancer / 肿瘤研究与临床

Objective:To investigate the value of prostate biopsy guided by transrectal real-time ultrasonic elastography (TRTE) combined with peak strain index (PSI) in the diagnosis of prostate cancer and the correlation with TRTE score and pathological Gleason score.Methods:A total of 80 patients with suspected prostate cancer who underwent TRTE in the First Affiliated Hospital of Hebei North University from January 2019 to December 2019 were selected. The PSI for suspicious lesions was measured, and targeted puncture biopsy guided by TRTE combined with PSI was performed on the patients, and then followed by systematic puncture biopsy. The outcomes of targeted biopsy and systematic biopsy were analyzed. Taking pathological biopsy results as the gold standard, the detection rates of prostate cancer and benign prostate lesions detected by both biopsies methods were compared; the prostate volume, serum prostate specific antigen (PSA) level and PSI were compared between patients with prostate cancer and benign prostatic lesions. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to determine the best cut-off value of PSI in the diagnosis of prostate cancer. The values of conventional ultrasound versus TRTE combined with PSI in the diagnosis of prostate cancer were assessed. The positive rate of biopsy puncture points under the guidance of TRTE combined with PSI was compared with that of systematic biopsy. The correlation between TRTE score and pathological Gleason score of prostate malignant lesions was analyzed.Results:Among 80 patients, 45 patients (56.25%) were diagnosed as prostate cancer by prostate puncture biopsy, and 35 patients (43.75%) were benign prostate lesions. Among 45 patients with prostate cancer, 42 cases (93.33%) of prostate cancer were detected by using TRTE combined with PSI-guided targeted puncture biopsy, and 38 cases (84.44%) of prostate cancer were detected by using systematic puncture biopsy; there was no significant difference in the detection rate of prostate cancer by both biopsies methods ( χ2 = 1.80, P = 0.180). The level of serum PSA and PSI value in the prostate cancer group were higher than those in the benign prostate lesion group, and the difference was statistically significant ( t value was 65.28 and 14.93, all P < 0.05). The clinical value of PSI value in the diagnosis of prostate cancer was analyzed by using ROC curve. The results showed that the AUC was 0.857 (95% CI 0.772-0.941), and the optimal cut-off value of PSI was 5.68; PSI ≥ 5.68 was treated as the malignant cancer and PSI < 5.68 was treated as the benign cancer. The sensitivity, specificity and accuracy of TRTE combined with PSI in the diagnosis of prostate cancer were 91.11%, 94.29%, and 92.50%, respectively, which were higher than those of conventional ultrasound (73.33%, 68.57% and 71.25%), and the differences were statistically significant (all P < 0.05). A total of 89 suspected lesions were detected in 80 patients through TRTE combined with PSI, and each suspected lesion was detected by using 2-needle targeted puncture biopsy. There were 178 needles in total including 88 needles of prostate cancer and the positive rate of puncture points was 49.44% (88/178); there were 800 needles in total detected by using 10-needle systematic puncture biopsy including 203 needles of prostate cancer and the positive rate of puncture points was 25.38% (203/800); the positive rate of puncture points guided by TRTE combined with PSI puncture biopsy was higher than that by systematic puncture biopsy, and the difference was statistically significant ( χ2 = 40.337, P < 0.05). For prostate malignant lesions, the Spearman correlation analysis showed that TRTE score was positively correlated with pathological Gleason score ( r = 0.618, P < 0.05). Conclusion:TRTE combined with PSI-guided targeted puncture biopsy plays an important role in the diagnosis of prostate cancer, and it can effectively improve the positive rate of puncture points.

Research progress of natural products for the treatment of hyperuricemia and gout / 药学学报

Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.

Medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

SUN's abdominal acupuncture for depression after methamphetamine withdrawal: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of SUN 's abdominal acupuncture and conventional acupuncture in the treatment of depression after methamphetamine withdrawal.@*METHODS@#A total of 80 female patients with depression after methamphetamine withdrawal were randomly divided into an observation group (40 cases, 1 case dropped off) and a control group (40 cases, 2 cases dropped off). The control group was treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 29), Taichong (LR 3), Shenmen (HT 7), Neiguan (PC 6), Danzhong (GV 17), and the observation group was treated with SUN 's abdominal acupuncture at area 1 of the abdomen and area 8 of the abdomen. Both groups were treated once a day, 30 min each time, 6 days as a course of treatment, 1 day rest between treatment courses, a total of 4 courses of treatment. The scores of withdrawal symptoms, Hamilton depression scale (HAMD), Pittsburgh sleep quality index (PSQI) scale and serum serotonin (5-HT) level were compared between the two groups before and after treatment.@*RESULTS@#After treatment, the scores of withdrawal symptoms, HAMD and the various scores and total score of PSQI scale in the two groups were all lower than before treatment (P<0.01), and the scores of withdrawal symptoms, HAMD and the sleep quality, time to fall asleep, sleep time scores and total score of PSQI in the observation group were lower than the control group (P<0.05, P<0.01). After treatment, the serum 5-HT level of the two groups was increased (P<0.01), and that in the observation group was higher than the control group (P<0.05).@*CONCLUSION@#SUN 's abdominal acupuncture can improve withdrawal symptom, depression and sleep quality, increase serum 5-HT content in treatment of depression after methamphetamine withdrawal, and has better effect than conventional acupuncture.

Anti-tumor mechanism of sesquiterpenoids from Cryptoporus volvatus based on molecular docking / 南方医科大学学报

OBJECTIVE@#To identify the target genes mediating anti-tumor effect of sesquiterpenoids from Cryptoporus volvatus and explore the possible mechanism using molecular docking and molecular dynamics simulation.@*METHODS@#Based on the chemical structure of sesquiterpenes from C. volvatus, we explored the online reverse target finding websites PharmMapper, SEA, Target Hunter and related literature for preliminary prediction of possible anti-tumor targets. Discovery Studio 4.0 (Libdock function) and Maestro 12.3 were used to connect sesquiterpenes with the possible targets, and the potential targets were selected according to the scores. The interaction between the sesquiterpenes and the targets were analyzed using 2D interaction diagram, and the influence of different sesquiterpene skeletons on their activity was inferred based on their activity measurements in experiment. Kinetic simulation was performed for front-end protein sequence (1UNQ) of the Akt (protein kinase B) and for the complex formed by 1UNQ and compound 4 (which had the best cytotoxic activity in vitro) in its optimal conformation, and the root mean square deviation (RMSD) value and root mean square float (RMSF) value of the complex and 1UNQ were measured to evaluate the stability of the binding of compound 4 to the target.@*RESULTS@#The sesquiterpenes showed optimal binding with 1UNQ. Analysis of 2D interaction diagram suggested that the hydrogen bonding and electrostatic force were the most important forces mediating the interaction between the sesquiterpenes and 1UNQ. Analysis of the optimal 3D conformation showed that for different sesquiterpenes, a slight change of the molecular framework produced a steric hindrance effect and caused changes in their bioactivity. Kinetic simulation showed that the complex formed by compound 4 and1UNQ had a lower RMSD than the target pure protein sequence, indicating that compound 4 could stably bind to 1UNQ. The anti-tumor effect of the sesquiterpenoids from C. volvatus was associated with their ability to cause Lys-144 acetylation, which blocks Akt binding to the downstream PIP3 and thus affects the proliferation of tumor cells.@*CONCLUSION@#1UNQ is the target of sesquiterpenoids from C. volvatus, which affects the proliferation of tumor cells by acetylating Lys-14.

The clinical value of shear wave elastography and salivary gland ultrasound scoring in salivary gland lesions of Sj?gren′s syndrome / 中华超声影像学杂志

Objective:To evaluate the value of shear wave elastography (SWE) and salivary gland ultrasound scoring(SGUS) system in the diagnosis of salivary glands lesions in patients with Sj?gren′s syndrome(SS) and to compare the diagnostic efficiency of the two methods.Methods:From June 2019 to November 2020, Fifty-eight patients with suspected SS were selected from the Affiliated Changzhou No.2 People′s Hospital of Nanjing Medical University. According to the 2002 American-European Consensus Group classification standard, the enrolled patients were divided into two groups: SS group (47 cases) and non-SS group(11 cases). According to symptom duration, SS group was divided into the ≤5 years group (29 cases) and the >5 years group (18 cases). Meanwhile, 40 healthy volunteers were enrolled in this study as normal control group. The diagnostic value of salivary gland ultrasound scoring system and Young′s modulus in SS were analyzed.Results:The differences in Young′s modulus of parotid gland and submandibular gland between SS group and non-SS group (or control group) were statistically significant (all P<0.05). The ultrasound score of SS group was significantly higher than that of non-SS group and control group (all P<0.05). SGUS and Young′s modulus were not significantly different between different course groups (all P>0.05). The areas under ROC curve of the mean Young′s value in parotid and submandibular gland and the SGUS were 0.801, 0.829 and 0.676, respectively. The comparison of the area under the curve between the Young′s modulus of the parotid and submandibular glands and the ultrasound score was statistically significant (all P<0.05). Conclusions:SWE and Ultrasonography scoring system have certain value in the diagnosis of salivary gland lesions in SS, and can provide important reference information for clinical diagnosis from different perspectives. The diagnostic efficiency of SWE for salivary glands lesions in patients with SS is better than that of SGUS scoring system.

Aerobic exercise suppresses hepatocellular carcinoma by downregulating dynamin-related protein 1 through PI3K/AKT pathway / 中西医结合学报

OBJECTIVE@#Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis.@*METHODS@#Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise.@*RESULTS@#The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 μmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor.@*CONCLUSION@#Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.

Protective effects of 7-hydroxyethyl chrysin on rats with exercise-induced fatigue in hypobaric hypoxia environment / 浙江大学学报·医学版

: To investigate the protective effect of 7-hydroxyethyl chrysin (7-HEC) on rats with exercise-induced fatigue in hypobaric hypoxic condition.Forty healthy male Wistar rats were randomly divided into four groups with 10 rats in each group: control group, model group, chrysin group and 7-HEC group. The rats in control group were raised at local altitude but other three groups were raised in a simulating altitude of for hypobaric hypoxia treatment. The chrysin group and 7-HEC group were given chrysin or 7-HEC by gavage for respectively; while the control group and model group were given the same amount of sterilized water. The weight-bearing swimming tests were performed 3 d later, and the weight-bearing swimming time was documented. After rats were sacrificed, the liver and skeletal muscle tissue samples were taken for pathological examination and determination of lactate, malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glycogen levels. Blood urea nitrogen was also determined. Compared with the model group, weight-bearing swimming times were significantly prolonged in 7-HEC group [ vs. (4.04±1.30) min, <0.01]; pathological changes in liver and skeletal muscle tissue were attenuated; generation rate of blood urea nitrogen vs. 0.60) mmol·L·min, <0.05], lactate [liver: (0.14±0.05) vs. (0.10±0.03) mg·g·min, skeletal muscle: vs. (0.18±] and MDA [liver: (0.48) vs. (0.78±0.28) nmol·mg·min, skeletal muscle: (0.87±0.19) vs. (0.63±0.11) nmol·mg·min] were significantly reduced (all < 0.05); glycogen content [liver: (15.16±2.69) vs. skeletal muscle: (1.46±0.49) vs.0.48) mg/g] and T-SOD [liver: (1.87±0.01) vs. (2.68±0.12) U/mL, skeletal muscle: 0.42) vs. 0.96) U/mL] were significantly improved (all <0.05). 7-HEC has significant protective effect on the rats with exercise-induced fatigue in hypobaric hypoxia condition.

Simultaneous quantitative analysis of nine saponins in Gynostemma pentaphyllum before and after heat processing based on UPLC-Q-Trap-MS / 中国中药杂志

Heat-processed Gynostemma pentaphyllum has strong biological activity, and saponins are the main components. To investigate the changes of saponins in G. pentaphyllum before and after heat processing, the present study determined and analyzed the content of nine saponins in G. pentaphyllum from Zhangzhou of Fujian and Jinxiu of Guangxi by ultra-high performance liquid chromatography with quadrupole ion-trap mass spectrometry(UPLC-Q-Trap-MS). The separation of the analytes was performed on an ACQUITY UPLC BEH C_(18) column(2.1 mm×50 mm, 1.7 μm) at 30 ℃, with acetonitrile and 0.1% formic acid in water as the mobile phase by gradient elution, and the flow rate was 0.3 mL·min~(-1). Quantitative analysis was performed using electrospray ionization source(ESI) in the multiple reaction-monitoring(MRM) mode. The results showed that the content of saponins with biological activities increased after heat processing. Specifically, gypenoside L, gypenoside LI, damulin A, damulin B, ginsenoside Rg_3(S), and ginsenoside Rg_3(R) in G. pentaphyllum produced in Zhangzhou of Fujian increased by 7.369, 8.289, 12.155, 7.587, 0.929, and 1.068 μg·g~(-1), respectively, while the content of ginsenoside Rd, gypenoside LVI, and gypenoside XLVI, which were abundant in the raw materials, decreased by 0.779, 19.37, and 9.19 μg·g~(-1), respectively. The content of gypenoside L, gypenoside LI, damulin A, damulin B, ginsenoside Rg_3(S), and ginsenoside Rg_3(R) in G. pentaphyllum produced in Jinxiu of Guangxi increased by 0.100, 0.161, 0.317, 0.228, 3.280, and 3.395 μg·g~(-1), respectively, while the content of ginsenoside Rd, gypenoside LVI, and gypenoside XLVI in the raw materials was reduced by 1.661, 0.014, and 0.010 μg·g~(-1), respectively. The results suggest that heat processing is an effective way to transform rare gypenosides. Furthermore, it is found that there are great differences in the content of gypenosides in different regions.

The role of renal 5-hydroxytryptamine synthesis and degradation in hyperglycemia-induced kidney injury / 药学学报

Hyperglycemic kidney injury (HKI) is a common complication of diabetic patients. We examined the relationship between HKI and the abnormal expression of 5-hydroxytryptamine (5-HT) system induced by hyperglycemia in type 2 diabetes mellitus (T2DM). In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT2A receptor (5-HT2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (respectively or in combination). In cell culture experiments, human glomerular mesangial cells (HMC) were stimulated with D-glucose (D-Glu), and 5-HT2AR, 5-HT synthesis, and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor clorgyline. Periodic acid-Schiff (PAS) staining and Masson staining, immunohistochemistry and Western blot, fluorescent probe, and enzyme linked immunosorbent assay (ELISA) and enzyme reagent were respectively used to detect histopathology, protein expression, intracellular reactive oxygen species (ROS), and biochemical indexes. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT2AR, 5-HT synthases, and MAO-A were expressed in glomerular basement membrane and kidney tubular epithelial cells of mouse kidney and HMC. The expression of these proteins was significantly up-regulated in T2DM mice or when HMC cells were exposed to high concentration of D-Glu. HKI, characterized by abnormal renal function, glomerular swelling, and glomerular basement membrane thickening and fibrosis, is closely associated with an increase in kidney 5-HT2AR, 5-HT synthesis, and 5-HT degradation. Among them, 5-HT2AR can mediate the expression of 5-HT synthases and MAO-A; MAO-A can catalyze the degradation of 5-HT to increase the production of mitochondrial ROS, leading to the phosphorylation of nuclear factor kappa B (NF-κB) with the production of inflammatory cytokines, and the up-regulation of matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) with the production of collagens. SH and CDP can effectively treat HKI, and the combination of SH and CDP has a clear synergistic effect.

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes / myoclonus epilepsy with ragged-red fibers /Leigh overlap syndrome caused by mitochondrial DNA 8344A>G mutation / 北京大学学报(医学版)

OBJECTIVE@#Mitochondrial deoxyribonucleic acid (mtDNA) 8344 A>G (m.8344A>G) mutation is the common mutation associated with mitochondrial myoclonus epilepsy with ragged-red fibers (MERRF) syndrome. Herein we report a rare case with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes/MERRF/Leigh (MELAS/MERRF/Leigh) overlap syndrome caused by m.8344A>G mutation.@*METHODS@#The clinical and imaging data of the patient were collected and an open muscle biopsy was carried out. We further employed molecular genetic analyses to detect mtDNA mutation in the proband and his mother. And then a clinical and neuroimaging follow-up was performed.@*RESULTS@#This patient was a 25-year-old male, who developed exercise intolerance since the age of 6. At age 10, he suffered from acute episodes of hemianopia, and cranial magnetic resonance imaging (MRI) showed occipital stroke-like lesions and cranial magnetic resonance spectroscopy (MRS) revealed a lactate peak corresponding to the lesion. After that the patient presented slowly progressive psychomotor decline. He had myoclonic seizures and cerebellar ataxia since the age of 12. At age 21, he was admitted to our hospital because of confusion and cranial MRI revealed symmetrical lesions in bilateral posterior putamen, thalami and midbrain. Then repeated MRI showed progression of original lesions and new frontal multiple stroke-like lesions. Symptomatic and rehabilitation treatment relieved his condition. Follow-up cranial MRI at age 24 showed the lesions in basal ganglia and thalami diminished, and the midbrain lesions even completely vanished. Muscle pathology indicated the presence of numerous scattered ragged-red fibers (RRF), suggestive of a mitochondrial disorder. Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) detected the m.8344A>G mutation of the MT-TK gene encoding mitochondrial transfer RNA for lysine in the patient's blood. Next generation sequencing (NGS) of the whole mitochondrial genome identified that the proportion of m.8344A>G was 90%, and no other mtDNA mutation was detected. Sanger sequencing further identified this mutation both in the proband and his mother's blood, although the mutation load was much lower in his mother's blood with approximately 10% heteroplasmy.@*CONCLUSION@#The present study is the first to describe a patient with m.8344A>G mutation in association with the MELAS/MERRF/Leigh overlap syndrome, which expands the phenotypic spectrum of the m.8344A>G mutation.

Protective effect of astaxanthin on the retinopathy of type 1 diabetic rats / 中华实验眼科杂志

Objective:To investigate the protective effect of astaxanthin on the retinopathy in rats with type 1 diabetes and related mechanism.Methods:Thirty-six male SPF rats received intraperitoneal injection of 1% streptozotocin (STZ) to prepare type 1 diabetes model.The rats were randomly assigned to the diabetes group, low dose astaxanthin group and high dose astaxanthin group by a random number table.The rats in the low dose astaxanthin group and high dose astaxanthin group received respectively astaxanthin 20 mg/kg and 100 mg/kg by gavage everyday.The rats in the diabetes group received an equal volume of olive oil.Twelve rats received an equal volume of sodium citrate as the control group.Blood glucose and body mass were measured every 2 weeks.After 24 weeks, the retina was digested to make retinal capillary network preparation.The number of pericytes and acelluar strands was compared among the different experimental groups.The relative expressions of anti-inflammatory cytokines in retinal tissue were detected by immunohistochemistry, real-time PCR and Western blot.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results:Body mass of the rats in the low dose astaxanthin group and high dose astaxanthin group was significantly higher than that in the diabetes group (both at P<0.05). Blood glucose levels in the low dose astaxanthin group and high dose astaxanthin group were significantly lower than that in the diabetes group (both at P<0.05). In the control group, main artery was round, uniform, and strongly stained.The vein was lightly stained and had a large diameter.In the diabetes group, retinal arteriovenous trunk and branches appeared tortuous at a low magnification, with capillary network disorder.The morphology of the capillaries showed pathology in the low dose astaxanthin group and high dose astaxanthin group, but the vascular tortuosity, dilatation and stenosis were reduced in comparison with the diabetes group.The number of pericytes was 466.4±23.2, 207.3±31.7, 298.1±27.1 and 312.2±19.5 among different groups, with a significant difference among them ( F=34.420, P=0.047). The number of acelluar strands were 5.2±2.3, 32.9±12.7, 14.5±9.1 and 16.5±3.5 among different groups, with a significant difference among them ( F=47.340, P=0.021). The relative expression of IL-6, TNF-α and caspase-3 mRNA in the low dose astaxanthin group was 0.87±0.23, 0.91±0.34 and 1.07±0.15, the relative expression in the high dose astaxanthin group was 0.81±0.31, 0.85±0.39 and 0.95±0.11, which was significantly decreased in comparison with the diabetes group (1.63±0.47, 1.57±0.53 and 1.51±0.32) (all at P<0.05). The relative expression of IL-6, TNF-α and caspase-3 protein in the low dose astaxanthin group was 0.63±0.33, 0.51±0.14 and 0.60±0.13, the relative expression in the high dose astaxanthin group was 0.69±0.22, 0.49±0.15 and 0.57±0.22, which was significantly decreased in comparison with the diabetes group (all at P<0.05). Conclusions:Astaxanthin may play an important role in protecting pericytes from apoptosis and delaying development and progression of diabetic retinopathy in rats.Additionally, astaxanthin can inhibit release of anti-apoptosis and anti-inflammatory cytokines.

Risk factors of obesity in children aged 5-14 years in Xuzhou and early intervention measures / 公共卫生与预防医学

Objective To explore the risk factors and early intervention methods of obesity in children aged 5-14 years in Xuzhou. Methods Children from 3 urban areas were randomly selected from Xuzhou City for physical measurement. The children were divided into obese group and normal group based on 2 standard deviations of WHO standard weight. A questionnaire survey was used to assess the risk factors for obesity in children aged 5 to 14, and early intervention measures were put forward. Results The detection rate of obese children in this group was 53.00%. Single factor analysis showed that breastfeeding, supplementary food addition at 4 and 6 months, fast eating, preference for dessert, drinks and fried foods, sleep time <8h/d, dislike of sports, daily TV watching time ≥ 2h / d, obesity of father and mother, mother's education level, and parents' obesity cognition were related to obesity in children aged 5-14 (P <0.05) . Logistic regression analysis revealed that artificial feeding, fast eating, deep frying, sweet drinks, mother's education, father's obesity and mother's obesity were high risk factors of children's obesity. Conclusion The incidence of obesity in children aged 5-14 years old in Xuzhou was high. Early feeding mode, children's preference for fried desserts, parents' obesity and mother's education level were the main risk factors for children's obesity. It is suggested that communities promote more health education on children’s obesity.