Panax ginseng is a precious medicinal herb both in China and abroad with high medicinal and economic value.Ginseng disease has been recognized as the main factor restricting its application.Modern molecular biology for the disease resistance of ginseng promoted the development of new methods.In this study,it was found that the antimicrobial proteins of ginseng involved lipid transfer protein,cyclophilin,defensins,PR-4 and PR-10,showing inhibitory effects on various pathogens.These findings provided a reference for the control of ginseng diseases.

To test the hypothesis that the first degree relatives of Chinese women with polycystic ovarian syndrome (PCOS) have higher risk of cardiovascular disease than those without PCOS.The metabolic phenotype and risks of cardiovascular disease were evaluated in 110 family members of 35 women with PCOS and 85 unrelated healthy control subjects without family history of diabetes and PCOS ( four age- and weight-matched subgroups ).The prevalence of impaired glucose tolerance was 51.4％ in mothers and 57.5％ in fathers with their daughters suffering from PCOS.The first degree relatives of PCOS women had significantly higher serum fasting insulin level,homeostasis model assessment for insulin resistance,insulin area under the curve,and lower insulin sensitivity index in all subgroups than the control subjects( P＜0.05 ).The control subjects had significantly elevated high molecular weight-adiponectin levels and decreased high sensitive-C reactive protein levels compared to the first degree relatives of PCOS women in all subgroups.Parents and brothers,but not sisters,of women with PCOS had significantly higher total cholesterol and low density lipoprotein-cholesterol ( P＜ 0.05 ),as well as triglyceride levels ( P＜ 0.05 ),compared with control subjects.The first degree relatives of PCOS women had features of insulin resistance and increased risk of cardiovascular disease.

Objective:To investigate the role of ferroptosis in calcium oxalate (Calcium Oxalate, CaOx) crystal-induced injury of human renal tubular epithelial cells (HK-2 cells).Methods:From March 2021 to September 2021, I used calcium oxalate crystal suspension to intervene HK-2 cells to build a HK-2-CaOx reaction model. Set the concentration gradient group and time gradient of calcium oxalate crystal intervention in HK-2 cells: 7 groups of calcium oxalate crystals with different concentrations (0, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 mmol/L) were used to intervene HK-2 cells24 hours, the HK-2 cell protein was extracted after the intervention; HK-2 cells were intervened with calcium oxalate crystals at optimum concentration, and extract proteins at different time points (0, 3, 6, 9, 12, 24, 48 h) after intervention, the expression of intracellular ferroptosis marker protein glutathione peroxidase 4 (GPX4) was detected by Western blot. Intervention of HK-2 cells with ferroptosis inducer Erastin and ferroptosis inhibitor ethyl 3-amino-4-cyclohexylaminobenzoate (Ferrostatin-1, Fer-1) to regulate intracellular ferroptosis Level. HK-2 cells were divided into 4 groups: normal control group (NC; no intervention treatment, cultured in complete medium only); calcium oxalate crystal stimulation group (CaOx; cultured in complete medium containing 4.0 mmol/L CaOx crystals); calcium oxalate crystals + erastine treatment group (CaOx+ Erastin; cultured in complete medium containing 10.0 μmol/L erastine and 4.0 mmol/L calcium oxalate crystals); calcium oxalate crystals + Fer-1 Treatment group (CaOx+ Fer-1; cultured in complete medium containing 1.0 μmol/L Fer-1 and 4.0 mmol/L calcium oxalate crystals). After 24 hours, the expression of ferroptosis-related protein GPX4, long-chain fatty acyl-CoA synthase 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) in HK-2 cells was analyzed by western blot and immunofluorescence techniques; the content of glutathione in HK-2 cells was detected; DCFH-DA fluorescence staining was used to observe the expression of reactive oxygen species (ROS) in HK-2 cells. The adhesion of calcium oxalate in HK-2 cells in each group was observed by light microscope, and the nuclear damage of HK-2 cells was detected by DAPI staining.Results:The expression levels of GPX4 in cells in the concentration gradient of 0, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 mmol/L were5.67±1.05, 5.60±0.02, 4.99±0.94, 4.82±0.93, 4.50±0.70, 4.14± 0.53, 0.97±0.53. The expression difference of GPX4 between the 4.0 mmol/L group and the 0 mmol/L group was statistically significant ( P=0.026). 4.0 mmol/L was selected as the optimal concentration to intervene the cells. The expression levels of GPX4 in the time gradient (0, 3, 6, 9, 12, 24, 48 h) cells were 11.73±1.29, 11.68±1.32, 11.72±1.30, 10.97±1.28, 10.63±1.21, 8.79±1.10, 8.03±1.06. The expression difference of GPX4 between the 24h intervention group and the 0h intervention group was statistically significant( P=0.090), so 24h was chosen as the optimal intervention time for calcium oxalate crystals. Compared with the NC group, the CaOx+ Erastin group had higher expression of ACSL4 (9.71±0.68 vs. 3.96±0.17, P<0.01); SLC7A11 (5.76±1.31 vs. 9.18±1.54, P=0.001) and GPX4 (3.61±0.25 vs. 9.26±0.13, P<0.01) the expression level decreased. Compared with the CaOx group, the CaOx+ Fer-1 group had higher protein expression levels of GPX4 (7.52±0.23 vs. 3.61±0.25, P<0.01), SLC7A11 (7.85±1.34 vs. 5.76±1.31, P=0.012), ACSL4 (5.84 ±0.62 vs. 9.71±0.68, P=0.002) protein expression was significantly decreased. Compared with CaOx group, CaOx+ Erastin group had significantly lower protein expression of GPX4 (2.71±0.18 vs. 3.61±0.25, P=0.001), SLC7A11 (3.82±1.60 vs. 5.75±1.31, P=0.017), ACSL4(11.15±0.44 vs.9.71±0.68, P<0.01) protein expression increased. The results of glutathione determination showed that compared with the NC group, the glutathione content in the CaOx group was significantly reduced [(53.38±3.53) mmol/L vs. (81.88±4.02) mmol/L, P<0.01]. Compared with the CaOx group, the CaOx+ Fer-1 group had significantly higher glutathione content [(68.26±4.55)mmol/L vs. (53.38±3.53)mmol/L, P=0.001]. Compared with the CaOx group, the glutathione content was decreased [(38.22±2.95)mmol/L vs.(53.38±3.53)mmol/L, P=0.01]. The results of DCFH-DA fluorescence staining showed that compared with the NC group (63.36±5.17 vs. 22.72±3.73, P<0.01), the CaOx group had a significantly higher fluorescence intensity, Compared with the CaOx group (45.32±4.33 vs. 63.36±5.17, P=0.002), the fluorescence intensity of cells in the CaOx+ Fer-1 group was significantly weakened, Compared with the CaOx group (82.38±6.25 vs.63.36±5.17, P=0.002), the fluorescence intensity of the cells in the CaOx+ Erastin group was significantly increased. The results of immunofluorescence showed that the CaOx group was significantly weakened compared with the NC group (31.63±2.86 vs. 50.36±4.23, P<0.01), and the CaOx+ Fer-1 group was significantly weakened compared with the CaOx group (39.89±3.35 vs. 31.63±2.86), P=0.038), the fluorescence intensity of cells in the CaOx+ Fer-1 group was significantly enhanced, the CaOx+ Erastin group was compared with the CaOx group (23.36±3.74 vs. 31.63±2.86, P=0.022), the cell fluorescence in the CaOx+ Erastin group was The intensity is significantly reduced. DAPI staining to calculate the damage ratio of each group of nuclei: NC group (2.85%), CaOx group (11.96%), CaOx+ Fer-1 group (8.76%), CaOx+ Erastin group (16.27%). Conclusion:CaOx crystals can induce ferroptosis in HK-2 cells by increasing the level of oxidative stress in HK-2 cells.

Objective:To analyze the clinical features of chronic active Epstein-Barr virus infection (CAEBV) in order to reduce the rates of underdiagnosis and misdiagnosis of this disease.Methods:The CAEBV related literatures of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, WanFang Database and Chongqing VIP since the first literature published (May 1987) until August 29, 2020 were searched. The clinical characteristics, laboratory examinations, outcome and causes of death of CAEBV patients were retrospectively analyzed. Statistical analysis was performed by Mann-Whitney U test, chi-square test or Fisher′s exact probability test. Results:A total of 111 patients aged 22.0 (10.0, 39.0) years were included from 46 articles. There were 64 cases (57.7%) in the age ≥18 years group and 47 cases (42.3%) in the age <18 years group. Fever, splenomegaly, hepatomegaly, and lymph node enlargement were common clinical manifestations, with incidences of 95.5%(106/111), 84.7%(94/111), 57.7%(64/111) and 56.8%(63/111), respectively. The incidences of rash and hepatomegaly in the age ≥18 years group were 3.1%(2/64) and 45.3%(29/64), respectively, which were both lower than those in patients aged <18 years group (27.7%(13/47) and 74.5%(35/47), respectively), while the incidence of abnormal liver biochemical indexes was higher (45.3%(29/64) vs 23.4%(11/47)). The differences were all statistically significant ( χ2=13.957, 9.436 and 5.643, respectively, all P<0.05). Of the 70 patients with follow-up outcomes, 38(54.3%) died and 32(45.7%) survived. The causes of death included gastrointestinal bleeding, severe infection, respiratory failure, liver failure, etc. The incidences of splenomegaly in the death and survival groups were 92.1%(35/38) and 68.8%(22/32), respectively. The difference was statistically significant ( χ2=6.266, P<0.05). Of 21 death and 17 survival cases in the age <18 years group, 15(71.4%) and two cases were combined hemophagocytic lymphohistiocytosis (HLH), respectively, with statistical significance ( χ2=13.527, P<0.01). Of the 90 patients whose HLH-related information was available, 38(42.2%) combined HLH and 52(57.8%) without HLH, with 36.8%(14/38) and 65.4% (34/52) of males, respectively. The difference of gender distribution was statistically significant ( χ2=7.187, P=0.007). The treatment regimens of the 111 CAEBV patients during the course of disease were various, but the detailed information was lacking. Conclusions:The clinical manifestations of CAEBV are diverse. CAEBV can be complicated with fatal complications, lacks of effective treatment, and shows poor prognosis. It is necessary to actively carry out related research to improve the understanding of the disease, and explore effective treatment and reduce mortality.

Objective The aim was to screen the expression profiles of microRNAs (miRNAs) in gastrointestinal stromal tumors (GIST) and explore the function of microRNA-301 a (miR-301 a). Methods Collected the tumor and adjacent normal tissues of 45 patients, who were diagnosed primary GIST. The expression profiles of tumor miRNAs in 5 of the 45 patients were obtained by microarray technology, and the abnormal expression levels of miRNAs in the remaining 40 patients were detected by Real Time-PCR as a validation experiment. Correlation analysis was analyzed between the significantly up-regulated expression of miR-301 a and the clinicopathological features of the patients. The MTT experiment was used to explore the effect of miR-301 a on the growth of GIST cell lines. Results Five kinds of miRNAs with high expression and five kinds of miRNAs with low expression were screened out from GIST, of which the expression of miR-301 a was up-regulated most obviously. The expression of miR-301 a was closely related to tumor risk grade, tumor size, mitosis and necrosis (P < 0.05). The overexpression of miR-301 a in GIST cell lines could significantly enhance the proliferation of cells. Conclusions MiR-301 a was up-regulated in GIST, which was closely related to malignant clinicopathological features and could affect the growth and proliferation of tumor cells in vitro. MiR-301 a might be a potential target for future treatment of GIST.

Ferroptosis is an iron-dependent, apoptotic cell death caused by massive lipid peroxidation-mediated cell membrane damage. Recent evidence suggests that exosomes, as a 30-100 nm diameter follicular body, contain a variety of active ingredients such as proteins, various RNAs and lipids that can have a great impact on the diagnosis and treatment of related diseases by regulating cellular iron death. To this end, this paper elaborates the research significance of exosomes in the regulation of cell ferroptosis, analyzes their role in disease treatment, and reviews the relevant reports and studies on exosomes regulating cell ferroptosis in recent years.

Objective:To investigate the effect of L-carnitine on calcium oxalate-induced ferroptosis in renal tubular epithelial cells (HK-2).Methods:The effects of calcium oxalate(0, 2, 4 and 8 mmol/L) on the expression of ferroptosis-related protein long chain fatty acyl-CoA synthetase 4 (ACSL4), cystine/glutamate transporter(XCT) and glutathione peroxidase 4 (GPX4) in HK-2 cells were detected by Western blotting. The experiment was then divided into four groups: ①control group, cells were cultured in normal medium for 12 hours, then continued to use normal medium; ②L-carnitine group, cells were pretreated with medium containing 5mmol/L L-carnitine for 12 hours, then changed to medium containing 5mmol/L L-carnitine; ③calcium oxalate group, cells were cultured in normal medium for 12 hours, and then replaced with medium containing 4 mmol/L calcium oxalate; ④calcium oxalate+ L-carnitine group, the cells were pretreated with medium containing 5mmol/L L-carnitine for 12 h, and then replaced with 5mmol/L L-carnitine and 4mmol/L calcium oxalate medium. After changing the culture medium for 24 hours, the cells or supernatants were collected, and the expression levels of ferroptosis-related protein quinone oxidoreductase (NQO1), ACSL4, XCT and GPX4 were detected by Western blotting. The levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde were detected by corresponding kit, and the level of reactive oxygen species in cells was detected by reactive oxygen species kit.Results:The results of Western blotting showed that the expression of ACSL4 protein in 0, 2, 4, 8 mmol/L calcium oxalate was 0.37±0.16, 0.68±0.16, 0.73±0.09, 0.89±0.03 respectively. The expression of XCT protein was 1.11±0.10, 0.91±0.14, 0.83±0.09, 0.80±0.07, respectively. The expression of GPX4 protein was 1.23±0.13, 0.99±0.17, 0.81±0.05, 0.72±0.06, respectively. Compared with 0mmol/L group, the expression of ACSL4 protein increased and the expression of XCT and GPX4 decreased in 2, 4 and 8 mmol/L groups, and the difference was more significant between 4 mmol/L group and 0 mmol/L group. So 4 mmol/L was taken as the optimal concentration for follow-up experiment. The levels of NQO1 in control group, L-carnitine group, calcium oxalate group and calcium oxalate+ L-carnitine group were (0.36±0.06, 0.54±0.05, 0.76±0.07, 0.90±0.03) respectively. There was significant difference between L-carnitine group and control group ( P<0.05). There was significant difference between calcium oxalate group and control group ( P<0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of ACSL4 in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (0.66±0.10, 0.58±0.08, 0.99±0.03, 0.77±0.09) respectively. There was no significant difference between L-carnitine group and control group(P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of XCT in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (0.93±0.08, 0.85±0.07, 0.76±0.06, 0.99±0.05). There was no significant difference between L-carnitine group and control group (P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of GPX4 in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (1.10±0.09, 1.09±0.09, 0.85±0.03, 0.99±0.02) respectively. There was no significant difference between L-carnitine group and control group( P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of LDH in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine were (100.00±5.37)%, (99.50±6.38)%, (153.77±6.06)% and (132.50±5.58)%, respectively. There was no significant difference between L-carnitine group and control group( P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The SOD levels in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (100.00±5.79)%, (105.80±3.26)%, (44.74±7.60)% and (85.01±5.15)%, respectively. There was no significant difference between L-carnitine group and control group( P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of GSH in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (100.00±4.73)%, (107.10±5.48)%, (53.49±3.98)% and (85.18±5.48)%, respectively. There was no significant difference between L-carnitine group and control group( P>0.01). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.01). The levels of MDA in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (100.00±2.36)%, (98.00±11.10)%, (129.11±2.59)% and (113.35±5.79)%, respectively. There was no significant difference between L-carnitine group and control group( P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.01). The fluorescence intensity of ferrous ion in control group, calcium oxalate group and calcium oxalate + L-carnitine group was (39.77±0.68) AU, (68.40±3.14) AU and (48.60±4.30) AU, respectively. There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The fluorescence intensity of reactive oxygen species in control group, calcium oxalate group and calcium oxalate + L-carnitine group was (63.98±9.41) AU, (145.41±8.39) AU and (85.37±4.51) AU, respectively. There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.01). Transmission electron microscopy results showed that mitochondria were wrinkled, cristae were broken or disappeared in the calcium oxalate group compared to the control group, and a double-layer membrane structure was evident. DAPI staining showed that compared with the control group, some of the nuclei in the calcium oxalate group were significantly more damaged, while compared with the calcium oxalate group, the nuclei in the calcium oxalate + L-carnitine were significantly less damaged. The results of crystal adhesion test showed that compared with the control group, calcium oxalate crystals in the calcium oxalate group adhered to the cells in black-like particles and formed clusters. Compared with the calcium oxalate group, the calcium oxalate + L-carnitine showed less black particles adhering to the cells. Conclusions:L-carnitine may reduce the effects of oxidative stress and ferroptosis induced by calcium oxalate, thus reducing cell damage and crystal adhesion.

BACKGROUND:Early postural adjustments serve as preparatory measures for forthcoming actions or potential disruptions in posture,thereby facilitating improved movement execution and mitigating destabilizing effects caused by posture interference. OBJECTIVE:To investigate the characteristics of temporal and intensity parameters of key lower limb muscles during early postural adjustment phase when stroke patients with varying levels of balance initiate walking at a self-selected comfortable pace. METHODS:The characteristics of early postural adjustments in 16 stroke patients were observed.Sixteen patients were divided into a non-fall group(n=8)and a fall group(n=8)based on the history of falls and Berg Balance Scale scores.Noraxon inertial sensors and Noraxon Ultium EMG wireless surface electromyography were utilized to collect body kinematic data and surface electromyography data during gait initiation.Muscle activation time and activation sequence of six key muscles in the lower limbs(tibialis anterior,medial and lateral gastrocnemius,rectus femoris,lateral femoris and biceps femoris muscles)during the early postural adjustment phase,as well as normalized electromyography integral values for the four time windows(each 150 ms)before gait initiation,were analyzed. RESULTS AND CONCLUSION:Stroke patients with a history of falls exhibited earlier activation times for the six key muscles in the lower limbs during gait initiation compared with those in the non-fall group.The fall group demonstrated significantly earlier activation times for tibialis anterior,lateral head of gastrocnemius,and vastus lateralis(P<0.01,P<0.05).In contrast,the non-fall group displayed a consistent pattern of activating extensor muscles before flexor muscles,with thigh muscle activation preceding calf muscle activation.However,in the fall group,calf extensor muscle activation occurred prior to thigh extensor muscle activation,and the vastus lateralis was activated even earlier.The tibialis anterior was the last activated muscle in both groups.Specifically during T3(>-300 to-150 ms),the tibialis anterior exhibited significantly higher activity in the fall group compared with the non-fall group(P<0.05),while the lateral head of gastrocnemius demonstrated significant inhibition during T3(P<0.05)and the medial head of gastrocnemius showed significant inhibition during both T3 and T4(>-150 to 0 ms)stages compared with the non-fall group(P<0.01,P<0.05).To conclude,stroke patients with varying balance abilities employ distinct early postural adjustment strategies prior to stepping,as evidenced by differences in muscle activation timing,recruitment order,and muscle activity amplitude.Patients at a high risk of falling exhibit prolonged duration of early postural adjustment and delayed initiation of gait,indicating earlier activation of the tibialis anterior muscle and inhibition of gastrocnemius muscle activity.These delays in gait initiation and variations in muscle recruitment strategies may contribute to unstable posture and an increased susceptibility to falls.

Porphyria is a disease caused by defects in the activity of any of the eight enzymes required for the heme synthesis pathway. Most of these are genetic diseases, and the main clinical symptoms are abdominal pain, neuropsychiatric symptoms and skin lesions. Detection of high levels of porphyrin and/or its precursors in blood, urine and feces can be used as diagnostic clues, and known genetic mutations can confirm the diagnosis. Porphyria is rare in clinical practice. However, in recent years, the number of porphyria patients with hepatic disease as the initial symptom has been increasing. Here, we focus on porphyria-related hepatic manifestations and their diagnosis and treatment, so as to provide recommendations for clinicians to reduce the misdiagnosis and missed diagnosis incidence rate.

With good prognosis of differentiated thyroid cancer (DTC), the 10-year survival rate of DTC patients is more than 90%. As a kind of radiation exposure, radioactive iodine (RAI) treatment has the potential to induce malignancies. Based on this view, whether RAI treatment will increase the risk of secondary primary malignancy (SPM) still has a lot of controversy. This review summarizes current situation of related researches, and also summarizes the limitations of the current researches and the problems to be solved in the future research. In this review, it is believed that RAI treatment does not increase the overall risk of SPM in postoperative-DTC patients.