Inhibition mechanism of cordycepin and ergosterol from Cordyceps militaris Link. against xanthine oxidase and cyclooxygenase-2.

Cordyceps militaris Link. (C. militaris) is an entomopathogenic fungus that parasitizes the pupa or cocoon of lepidopteran insect larvae, with various bioactive compounds. Cordycepin and ergosterol are the two active components in C. militaris. This study aimed to evaluate the inhibitory activity of cordycepin and ergosterol against xanthine oxidase (XO) and cyclooxygenase-2 (COX-2), as well as investigate the inhibition mechanism. Cordycepin could better inhibit XO (IC50 = 0.014 mg/mL) and COX-2 (IC50 = 0.055 mg/mL) than ergosterol. Additionally, surface hydrophobicity and circular dichroism (CD) spectra results confirmed the conformational changes in enzymes induced by cordycepin and ergosterol. Finally, cordycepin and ergosterol significantly decreased uric acid (UA) and inflammatory factors to normal level in mice with gouty nephropathy (GN). This study could provide theoretical evidence for utilization of C. militaris in hyperuricemia-management functional foods.

Socio-economic disparities in exposure to and endorsement of COVID-19 vaccine misinformation and the associations with vaccine hesitancy and vaccination.

OBJECTIVES: We examined disparities in vaccine misinformation exposure and endorsement and the associations with vaccine hesitancy and vaccination uptake. STUDY DESIGN: Population-based survey. METHODS: A population-based survey was conducted on 5,002 Hong Kong adults oversampling low socio-economic status (SES, n = 2,200). Information on exposure (13 misinformation statements, total 0-13, median = 2), endorsement (13 statements, score 0-10, high scores indicate higher levels of endorsement, median = 5.75) of misinformation, vaccine hesitancy (14 items, score 1-5), and vaccination (two doses) were collected. Multivariable regression (adjusted ß [aß]) and Poisson regression (adjusted risk ratio [aRR]) adjusting for demographic characteristics were used to examine the associations of exposure to and endorsement of misinformation with vaccine hesitancy and vaccination. RESULTS: A total of 71.8% of respondents had at least exposure to one vaccine misinformation, and 35.7% had a high level of endorsement (median or above). Respondents with lower SES had a lower exposure (≤2 statements, 57.1% vs 50.1%, P < 0.001) but a higher level of endorsement (36.6% vs 34.9%, P = 0.01) of misinformation. Overall, 72.9% had been vaccinated for two or more doses, with a lower proportion in respondents with lower SES (83.6% vs 61.1%; P < 0.001). Compared with no exposure to misinformation, high levels of exposure and endorsement were associated with vaccine hesitancy (aß = 0.44, 95% confidence interval 0.40-0.48; aß = 0.50, 0.47-0.54, respectively) and lower vaccination rates (aRR = 0.98, 0.97-0.99; aRR = 0.92, 0.88-0.96, respectively). Vaccine hesitancy mediated the associations of exposure (fully, 100%) and endorsement (partially, 73%) with vaccination uptake. CONCLUSION: Endorsement of vaccine misinformation in respondents with lower SES was associated with low vaccination uptake.

[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

[A retrospective controlled study of TACE-HAIC-targeted-immune quadruple therapy for intermediate and advanced-stage hepatocellular carcinoma].

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ2 test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.

[Safety and efficacy of TIPS combined with iodine-125 seed strands in the treatment of patients with hepatocellular carcinoma combined with portal vein tumor thrombosis].

Objective: To study the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with iodine-125 (125Ⅰ) seed strands implantation in patients with hepatocellular carcinoma combined with portal vein tumor thrombosis. Methods: 25 cases with diffuse intrahepatic tumor combined with tumor thrombus type Ⅲ/Ⅳ requiring TIPS were simultaneously implanted with 125Ⅰseed strand. Tumor thrombus was controlled with 125I seed implantation brachytherapy to keep the TIPS pathway unobstructed, reduce the portal vein pressure, and observe the changes in the cause of death of the patients. During the same period, 30 cases without TIPS and seed strand implantation were used as controls. Data between groups were compared using t-test, Chi-Squared test or Fisher's exact test. Results: TIPS combined with 125Ⅰ seed strand implantation was safe in patients with diffuse hepatocellular carcinoma combined with type III/IV portal vein tumor thrombus, and 92.0% (23/25) of the patients maintained unobstructed TIPS pathway. Compared with the control group, patients in the treatment group died of fewer lead-related complications, and most died from chronic liver failure (84.0% vs. 56.7%, χ2 = 4.771, P=0.029). The incidence of upper gastrointestinal bleeding was significantly decreased (12.0% vs. 46.7%, χ2 =7.674, P=0.006) and ascites severity was significantly improved (mild 40.0% vs. 16.7%, moderate 52.0% vs. 20.0%, severe 8.0% vs. 46.7%, χ2 =13.246 , P=0.001). Conclusions: TIPS combined with 125Ⅰ seed strand implantation is safe and feasible in patients with diffuse intrahepatic tumor combined with tumor thrombus type Ⅲ/Ⅳ. Moreover, it can effectively keep the shunt patency and reduce portal vein pressure, thereby reducing the incidence of upper gastrointestinal bleeding and improving the degree of ascites. TIPS combined with 125Ⅰ seed strand implantation may be used as a standard treatment modality for patients requiring TIPS therapy combined with tumor thrombus type Ⅲ/Ⅳ.

[Percutaneous biliary stent combined with brachytherapy for malignant obstructive jaundice: a multicenter retrospective controlled study].

Objective: To investigate the efficacy, safety and prognostic factors of percutaneous biliary stent combined with iodine-125 seed chain brachytherapy (radiotherapy) in the treatment of malignant obstructive jaundice. Methods: Data of 107 cases with malignant obstructive jaundice treated with percutaneous biliary stent implantation from January 2017 to December 2020 were retrospectively analyzed. Among them, 58 cases received biliary stent combined with iodne-125 seed chain brachytherapy (study group), and 49 cases received biliary stent implantation (control group). The changes of bilirubin, stent patency time, complications, overall survival (OS) and prognostic factors were analyzed in both groups. Results: The incidence of complications in the study group and the control group were 17.2% and 18.3% respectively, and the difference was not statistically significant (P=0.974). Serum total bilirubin levels were decreased significantly in both groups at one month after surgery (P<0.001). Postoperative stent patency time was significantly better in the study group (10.0±1.6 months) (95% CI: 8.2～12.5) than that in the control group (5.2±0.4 months) (95% CI: 4.1～6.0, P<0.001). The median OS was longer in the study group (11.2±1.8 months) (95% CI: 9.2～12.8) than that in the control group (8.0±1.1 months) (95% CI: 8.0～12.8, P<0.001). Multivariate analysis result showed that stent combined with brachytherapy (HR=0.08, 95% CI:0.04～0.15, P<0.001) and receiving further anti-tumor therapy after surgery (HR=0.27, 95% CI:0.15~0.49, P<0.001) were independent risk factors affecting the patency of biliary stents. Preoperative percutaneous transhepatic biliary drainage (HR=0.46, 95%CI:0.28～0.74, P=0.002), stent combined with brachytherapy (HR=0.23, 95%CI:0.14～0.39, P<0.001) and receiving further anti-tumor therapy after surgery (HR=0.37, 95%CI:0.22～0.61, P<0.001) were independent risk factors affecting OS. Conclusion: Percutaneous biliary stent combined with brachytherapy is safe and effective in the treatment of malignant obstructive jaundice, which can significantly prolong the patency time of biliary stent and the survival time of patients.

[Multicenter retrospective study of 38 cases with fumarate hydratase deficiency uterine leiomyoma].

Objective: To investigate the clinicopathological features of fumarate hydratase (FH) deficiency uterine leiomyoma. Methods: The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed. The expressions of FH, S-(2-succino)-cysteine (2SC), desmin, p16, p53, CD10 and cell proliferation associated nuclear antigen (Ki-67) proteins were detected by immunohistochemistry, and their clinicopathological features were analyzed retrospectively. Results: (1) Clinical features: the median age of the patients was (42.5±7.4) years old. Twenty-one cases (55%) of them were myomas found in physical examination, and the median maximum diameter of the tumor was 6.0 cm (range: 5.0-7.5 cm); myomectomy was performed in 23 cases (61%), total hysterectomy with or without bilateral appendages in 15 cases (39%); laparoscopic surgery in 27 cases (71%), open surgery in 11 cases (29%); none of the patients had renal cell carcinoma. (2) Histological features: atypical nuclear cells were distributed locally or diffusely, eosinophilic nucleoli and intranuclear inclusion bodies could be seen, glass like globules could be seen in the cytoplasm, nuclear division was 0-4/10 high power field (HPF), and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma. Among 38 patients with FH deficiency uterine leiomyoma, FH was negative in 37 cases (97%), and positive in 1 case (3%); 2SC, desmin, p16, p53, CD10 and Ki-67 showed focal positive expression in 38 cases (100%), including 35 cases (92%) with Ki-67 index<10% and 3 cases (8%) with Ki-67 index ≥10%. (3) Follow-up: 4 cases (11%) recurred, and there was no death. There were significant differences in age, family history, distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group (all P<0.05). Conclusions: FH deficiency uterine leiomyoma is a rare tumor, which needs pathological examination,immunohistochemical examination and clinical history. Patients younger than 43 years old, with family history, histologically atypical diffuse nuclear distribution and mitotic number ≥3/10 HPF should be alert to the risk of recurrence.

[Investigation on population dynamics and Echinococcus infections in small rodents around human settlement in Yushu City, Qinghai Province].

OBJECTIVE: To investigate the population dynamics and Echinococcus infections in small rodents around human settlement in Yushu City, Qinghai Province. METHODS: Rodents were captured using the mouse trap method in pastures from Batang Township and Longbao Township of Yushu City, Qinghai Province on May, August and October, 2018. The body weight and snout-vent length of all captured rodents were measured, and the species was identified according to the rodent morphology. Genomic DNA was extracted from rodent liver specimens and lesion specimens, and the mitochondrial cox1 gene of Echinococcus was amplified using PCR assay for identification of parasite species. In addition, the tissue specimens positive for PCR assay were sampled for pathological examinations. The prevalence of Echinococcus infections was estimated in rodents, and a phylogenetic tree was created based on Echinococcus cox1 gene sequences. RESULTS: A total of 285 small rodents were captured, including 143 Ochotona curzoniae (50.2%), 141 Lasiopodomys fuscus (49.5%), and 1 Neodon irene (0.3%), and there was a remarkable variation in habitat selection among these three rodent species. The number of L. fuscus correlated positively with vegetation coverage (r = 0.350, P = 0.264), with the greatest number seen in August, and the number of O. curzoniae negatively with vegetation coverage (r = -0.371, P = 0.235), with the highest number seen in August and the lowest number in May. The female/male ratios of O. curzoniae and voles were 1:0.96 and 0.82:1, respectively. The body weight (r = 0.519, P < 0.01) and snout-vent length (r = 0.578, P < 0.01) of O. curzoniae showed a tendency towards a rise with month, while the body weight (r = -0.401, P < 0.01) and snout-vent length (r = -0.570, P < 0.01) of voles presented a tendency towards a reduction with month. No Echinococcus infection was detected in voles, while 2.1% prevalence of E. shiquicus infection was seen in O. curzoniae. Phylogenetic analysis revealed consistent sequences of cox1 gene from E. shiquicus in Yushu City of Qinghai Province and Shiqu County, Ganzi Tibetan Autonomous Prefecture of Sichuan Province. CONCLUSIONS: The small rodents around the human settlement in Yushu City of Qinghai Province mainly include O. curzoniae and L. fuscus, with the greatest numbers seen in May and August, respectively. Following the concerted efforts for echinococcosis control, the prevalence of Echinococcus infections is low in small rodents around the human settlement in Yushu City; however, there is still a risk of echinococcosis transmission.

[Influences of gas explosion on acute blast lung injury and time phase changes of pulmonary function in rats under real roadway environment].

Objective: The aims of this study were to investigate the effect of gas explosion on rats and to explore the pulmonary function alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment. Methods: In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the real gas explosion roadway environment, fixed the cage and set the explosion parameters. 72 SD rats, male, SPF grade, were randomly divided into nine groups by completely random grouping method according to their body weight: control group, close range group (160 m) , and long range group (240 m) . In each group, there were wound groups (24 h group and 48h group, 8/group, total 48 in six groups) and no wound groups (8/group, total 24 in three groups) . Except for the control group, the other groups were placed in cages at different distances under anesthesia, the experiment of gas explosion was carried out by placing the rats in a position that could force the lungs. The changes of respiratory function of the rats in the non-invasive group were monitored with pulmonary function instrument at 2 h, 24 h, 48 h, 72 h and 168h after the explosion, and were killed under anesthesia 7 days later; the rats in invasive groups were anesthetized and killed at 24 h, 48 h and 168 h, respectively. Gross observation, lung wet-dry ratio and lung histopathology were performed. Results: Compared with the control group, f (respiratory frequency, f) , MV (minute ventilation, MV) , PEF (peak expiratory flow rate, PEF) , PIF (peak inspiratory flow rate, PIF) and EF50 (1/2 tidal volume expiratory flow, EF50) of rats in the close and long range groups decreased significantly after gas explosion 2 h. PAU (respiration pause, PAU) , Te (expiratory time, Te) , Ti (inspiratory time, Ti) and Tr (relaxation time, Tr) were significantly increased (P<0.05) . After 48 h, TV (tidal volume, TV) , Penh (enhanced respiration pause, Penh) , PAU, and PIF of rats in the long range group were significantly increased (P<0.05) . After 72 h, MV in the long range group was significantly decreased (P<0.05) . Compared with the control group, Penh, PAU, Ti and Te were significantly decreased after 168 h in the close and long range groups, with statistical significance (P<0.05) . At the same time, the body weight of rats in different range groups was significantly decreased (P<0.05) . In addition, both HE staining and routine observation of lung tissues of rats in different range groups showed that gas explosion caused pulmonary edema, obviously congested pulmonary capillaries, a large number of inflammatory cells and infiltrated red blood cells. Conclusion: Gas explosion in real roadway environment can cause the change of respiratory function phase and lung tissue damage in rats, suggesting that the model of gas explosion-induced ABLI has been initially established successfully, which would provide a basis for further study on the pathogenesis of ABLI.

Effects of evaporative cooling and dietary zinc source on heat shock responses and mammary gland development in lactating dairy cows during summer.

The objective of this study was to examine the effects of evaporative cooling and dietary supplemental Zn source on heat shock responses and mammary gland development of lactating dairy cows during summer. Seventy-two multiparous lactating Holstein cows were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement. Cows were either cooled (CL) or not cooled (NC) and fed diets supplemented with 75 mg of Zn/kg of dry matter (DM) from Zn hydroxychloride (IOZ) or 35 mg of Zn/kg of DM from Zn hydroxychloride plus 40 mg of Zn/kg of DM from Zn-Met complex (ZMC). The 168-d trial included a 12-wk baseline phase when all cows were cooled and fed respective dietary treatments, and a subsequent 12-wk environmental challenge phase when NC cows were deprived of evaporative cooling. Plasma was collected from a subset of cows (n = 24) at 1, 3, 5, 12, 26, 41, 54, 68, 81 d of the environmental challenge to measure heat shock protein (HSP) 70 concentration. Mammary biopsies were collected from another subset of cows (n = 30) at enrollment (baseline samples) and at d 7 and 56 of the environmental challenge to analyze gene expression related to heat shock response, apoptosis and anti-oxidative enzymes, and to examine apoptosis and cell proliferation using immunohistochemistry. Supplemental Zn source did not affect milk yield but NC cows produced less milk than CL cows. Supplemental Zn source had no effect on mammary gene expression of HSP27, 70, and 90 or plasma concentrations of HSP70. The NC cows had greater mammary gene expression of HSP than CL cows. Circulating HSP70 of NC cows gradually increased and was higher at 81 d of environmental challenge compared with CL cows. Relative to IOZ, ZMC cows tended to have lower total mammary cell proliferation but greater mammary apoptosis. There was a tendency of greater TNFRSF1A mRNA expression for ZMC compared with IOZ cows, which may suggest upregulated extrinsic apoptosis. At d 7 of environmental challenge, NC cows had numerically higher mammary apoptosis than CL cows although not statistically significant. The NC cows tended to have greater mRNA expression of CAT and SOD3 regardless of time, and had greater mRNA expression of GPX1 at d 56 and FAS at d 7 of the environmental challenge than CL cows. Relative to CL cows, mammary cell proliferation rate was higher for NC cows at d 56 of the environmental challenge. In conclusion, dietary source of supplemental Zn has substantial effect on mammary cell turnover in lactating dairy cows, and prolonged exposure to heat stress increases mammary cell proliferation.

Effect of feeding linseed diet on testis development, antioxidant capacity, and epididymal cauda sperm concentration in Chinese Hu lamb.

Polyunsaturated fatty acids (PUFAs) are essential for mammalian testis development and sperm function. However, PUFAs that are contained in linseed oil are easily oxidized in the diet and biohydrogenated in the rumen. In this study, we investigated the effect of linseed as a source of PUFAs on the antioxidant capacity and testis development in Hu lamb. Seventy-five 3-month-old lambs were randomly assigned to three groups. Within each treatment group, 25 lambs were allocated to five pens (five lambs per pen). The lambs in the control group were fed a control diet without linseed for 42 days from D22 to D63. Group I (BS28) was fed a control diet from D22 to D35 and 8% linseed diet from D36 to D63. Group II (BS42) was fed an 8% linseed diet for 42 days from D22 to D63. After 63-day feeding trial, all lambs except the heaviest and lightest in each pen were humanely slaughtered and investigated. Results revealed that feeding linseed did not affect the body weight, scrotal circumference, and testis weight, whereas feeding linseed for 42 days increased the epididymis weight (37.85 ± 1.61 g vs. 32.09 ± 1.06 g, P < 0.05) compared with the control group. Feeding lambs with linseed for 42 days also significantly upregulated the expression of antioxidative (glutathione peroxidase 4 and copper-zinc superoxide dismutase), steroidogenesis (3ß-hydroxysteroid dehydrogenase and steroid acute regulatory protein), and PUFA metabolism-related genes (fatty acid desaturase 2 and elongation of very long-chain fatty acid protein 2) and proliferating cell nuclear antigen mRNA (P < 0.05). It also increased the relative expression of mitochondrial DNA (P < 0.05), total antioxidant capacity (0.230 ± 0.019 mmol/mgprot vs. 0.175 ± 0.011 mmol/mgprot, P < 0.05), and superoxide dismutase (1661.467 ± 147.117 U/mgprot vs. 1158.891 ± 98.850 U/mgprot, P < 0.05) in testicular tissue but decreased the cholesterol concentration (0.331 ± 0.073 mmol/mgprot vs. 0.671 ± 0.092 mmol/mgprot, P < 0.05) compared with the control group. Therefore, feeding lambs with linseed for 42 days stimulated seminiferous tubule development and increased the number of Sertoli cells (20.71 ± 0.89 vs. 17.6 ± 0.73, P < 0.05), epididymal cauda lumina diameter (638.26 ± 22.32 µm vs. 444.41 ± 34.80 µm, P < 0.05), and the number of sperm in the epididymal cauda (68.91 ± 7.06 × 108/g vs. 36.61 ± 7.50 × 108/g). All these results suggested that feeding linseed in the early reproductive development stage of lambs upregulated the expression of antioxidative, steroidogenesis, and PUFA metabolism-related genes; increased the antioxidant capacity in lamb's testis; and contributed to testis development and spermatogenesis.

[Orthopedic treatment of musculoskeletal disorders in hemophilic patients].

Objective: To study the orthopedic treatment strategy for hemophilia complicated with musculoskeletal disorders as well as the peri-operative consumption of clotting factor. Methods: Total 338 orthopedic surgeries were performed for 261 patients, average age of 30.6 y (6-65 y) , with hemophilia between January 1996 and December 2019 at our institute. Two hundred and twenty-six patients presented with bleeds within the joints. Sixty-one patients presented with intramuscular bleeds, 45 presented with hemophilic pseudotumors, and six presented with miscellaneous complaints. Strategy of clotting factor replacement therapy was designed as per differences in the level of the operation procedure. Information regarding clinical manifestation, operative strategy, clotting factor consumption, and re-operation for complications was retrospectively recorded. The costs for multiple joint procedure and single joint procedure were studied. Results: We found that 270 of the 338 surgical procedures were major surgical procedures (79.9%) . There were 203 procedures of joint arthroplasty (60%) . Fourteen patients underwent reoperations for local recurrence (4.2%) . The average factor Ⅷ consumption before the surgery was 44.4 ± 8.1 IU/kg. The average FⅧ consumption within postoperative 2 weeks was 40 962 IU (647±177 IU/kg) . Seven type A hemophilic patients developed F Ⅷ inhibitor following the surgical procedure, with an average level of 13.7±11.2 BU/mL. Sixty-eight patients underwent multiple joint procedures under one anesthesia session (26%) . There was no significant difference in the factor consumption between the multiple joint procedure and single joint procedure. Conclusions: Surgical treatment was found to be effective for hemophilic arthropathy and lesion of the musculoskeletal apparatus, with the clotting factor replacement therapy. Multiple joint procedures under one anesthesia were more cost effective for patients with hemophilia, with less factor consumption than staged single joint procedure.

[An interpretation of drug Fei Lian() in the Prescription for Nurturing Vitality and the culture connotation of Fei Lian()].

The drug Fei Lian() in the unearthed medical book the Prescription for Nurturing Vitality () has been interpreted as Fei Lian(, an insect medicine) in Shennong Bencao Jing(, Shennong's Classic of Materia Medica). This article interprets it as herbal medicine Fei Lian(), not insect medicine Fei Lian() in Shennong Bencao Jing, based on the mutual evidence of unearthed documents and handed down documents, also the methods of phonology and exegesis. The word "Fei Lian" has rich cultural connotations, its etymology is related to "wind" , its semantics has the meaning of "light and fast speed" . It is used as the name of related totem image, legendary figures, historical figures, medicines, architecture and so on.

Circular RNA_LARP4 inhibits cell migration and invasion of prostate cancer by targeting FOXO3A.

OBJECTIVE: The importance of circular RNAs in malignant tumors causes more attention in researchers. Circular RNA_LARP4 is identified as a tumor suppressor in gastric cancer, but the role of circular RNA_LARP4 in prostate cancer (PCa) remains unclear. Our work aims to uncover whether and how circular RNA_LARP4 functions in the PCa development. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to determine the level of circular RNA_LARP4 in PCa tissues and cell lines. The patients' prognosis was analyzed. Circular RNA_LARP4 lentivirus was constructed for transfection of PCa cells. Cell migrated and invaded ability was detected through wound healing assay and transwell assay. Western blot assay was performed to analyze the protein level of FOXO3A. RESULTS: The low circular RNA_LARP4 expression was associated with poor prognosis of PCa patients. The circular RNA_LARP4 was lowly expressed in PCa tissues compared with adjacent samples. The expression of circular RNA_LARP4 was downregulated in PCa cell lines. The cell migrated and invaded ability of PCa cells was inhibited after circular RNA_LARP4 was overexpressed. Furthermore, FOXO3A expression was increased via the overexpression of circular RNA_LARP4. CONCLUSIONS: Circular RNA_LARP4 could suppress cell migration and invasion of PCa by upregulating FOXO3A.

Clinical effectiveness of 3 days preoperative treatment with recombinant human erythropoietin in total knee arthroplasty surgery: a clinical trial.

AIMS: The purpose of study is to evaluate the effect and complication of preoperative short-term daily recombinant human erythropoietin (rhEPO) treatment for blood-saving in patients undergoing unilateral primary total knee arthroplasty (TKA). METHODS: This three-arm randomized clinical trial compared three different rhEPO-based treatment protocols for unilateral primary TKA. Group A: application of daily doses of rhEPO combined with iron supplement starting 3 days before surgery; Group B: application of daily doses of rhEPO combined with iron supplement starting the day of surgery; Group C: iron supplement alone. Perioperative hemoglobin (Hb) level gaps, total perioperative blood loss, reticulocyte levels and treatment-related complications were studied. RESULTS: A total of 102 patients were included (35, 35 and 32 patients in Groups A, B and C, respectively). Total blood loss (TBL) in Groups A, B and C was 490.84, 806.76 and 924.21 ml, respectively. Patients in Group A had a significant lower TBL than Groups B and C (A vs. B: P = 0.010; A vs. C: P < 0.001). There was no difference as for TBL between Groups B and C (P = 0.377). Group A patients had significant smaller Hb decline than Group C on the third and fifth postoperative day (P = 0.049, P = 0.037), as well as than Group B on the fifth postoperative day (P = 0.048). There was no difference as for Hb decline between Groups B and C. No difference was shown in levels of inflammatory biomarkers or blood-saving protocol-related complications among three groups. CONCLUSIONS: Daily dose of rhEPO combined with iron supplement administered 3 days before TKA procedures could significantly decrease perioperative blood loss and improve postoperative Hb levels, without significantly elevating risks of complication, when compared with admission of rhEPO on the day of surgery and iron supplement alone. Preoperative daily rhEPO treatment could be a more effective blood-saving protocol in TKA procedures.

Porcine insulin receptor substrate 2: molecular cloning, tissues distribution, and functions in hepatocyte and aortic endothelial cells.

Insulin receptor substrate 2 (IRS-2) modulates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which controls the suppression of gluconeogenic genes; IRS-2 is also a critical node of insulin signaling. Because of the high homology between pig and human IRS-2, we investigated the expression pattern and function of porcine IRS-2. QPCR and immunoblotting were used to detect the IRS-2 expression level in different tissues. There were high IRS-2 levels in the cerebral cortex, hypothalamus, and cerebellum in the central nervous system. In peripheral tissues, IRS-2 was expressed at relatively high levels in the liver. Immunohistochemistry analysis revealed that IRS-2 was mainly distributed in the hypothalamus and cerebral cortex. Furthermore, IRS-2 knockdown porcine hepatocytes and porcine aortic endothelial cells (PAECs) were generated. The IRS-2 knockdown induced abnormal expression of genes involved in glycolipid metabolism in hepatocytes and reduced the antiatherosclerosis ability in PAECs. In addition, we disrupted IRS-2 in porcine embryonic fibroblasts (PEFs) using the CRISPR/Cas9 genome editing system, before finally generating IRS-2 knockout embryos by somatic cell nuclear transfer (SCNT). Taken together, our results indicate that IRS-2 might be a valuable target to establish diabetes and vascular disease models in the pig.