Exploring the potential mechanism of artesunate in intervening with U87 cells and U251 cells with distinct therapeutic effects on the basis of transcriptome sequencing and network pharmacology / 药学学报

Artesunate possesses the potential of intervening with glioma, however, its pharmacological mechanisms remain unclarified. Firstly, the effects of artesunate on cell activity, proliferation and apoptosis of U87 and U251 human glioma cells were explored. It was found that artesunate exerted stronger inhibitory effects on the activity and proliferation of U87 cells than U251 cells. It could significantly promote apoptosis in U87 cells (P < 0.05), while only high dose of artesunate can promote that of U251 cells (P < 0.01), detected by Hoechst and TUNEL cell apoptosis staining. Further, the differential expression gene sets between artesunate-sensitive and non-sensitive cell line, as well the therapeutic effects-related genes of artesunate were obtained through transcriptome sequencing and differential data analysis by using the lysates of U87 and U251 cells before and after artesunate treatment, aiming to explore the molecular mechanism of distinct artesunate sensitivity to two types of cells. Then, key putative targets that related to therapeutic effects were screened by constructing the interaction network of differential genes of three above comparison groups, and calculating their topological characteristics. Pathway enrichment analysis showed that those key putative targets were significantly enriched in several signaling pathways that were closely associated with the main pathological changes of glioma, among which apoptosis-related activating transcription factor 4 (ATF4)-DNA damage induced transcript 3 (DDIT3)- polyadenosine diphosphate ribose polymerase 1 (PARP1) signaling axis was the most enriched in. Molecular docking indicated that artesunate had fine binding affinities with ATF4 and DDIT3. Above all, this study preliminarily revealed that ATF4-DDIT3-PARP1 signaling axis is the target pathway of artesunate intervening with U87 glioma cells, and PARP1 may be an important gene for U251 cells to develop resistance to artesunate. Our results not only provide fundamental experimental evidence for artesunate as a potential therapeutic drug in glioma treatment, but shed light into overcoming drug resistance in its clinical therapy.

Usefulness of Simultaneous Magnetic Resonance Neurography and Apparent T2 Mapping for the Diagnosis of Cervical Radiculopathy

Methods@#A total of 14 patients with unilateral radicular symptoms and five healthy subjects were subjected to simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement signaling (SHINKEI-Quant) using a 3-Tesla magnetic resonance imaging. The Visual Analog Scale (VAS) score for neck pain and upper arm pain was used to evaluate clinical symptoms. T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus were measured bilaterally from C4 to C8 in patients with radicular symptoms and from C5 to C8 in healthy controls. The T2 ratio was calculated as the affected side to unaffected side. @*Results@#When comparing nerve roots bilaterally at each spinal level, no significant differences in T2 relaxation times were found between patients and healthy subjects. However, T2 relaxation times of nerve roots in the patients with unilateral radicular symptoms were significantly prolonged on the involved side compared with the uninvolved side (p<0.05). The VAS score for upper arm pain was not significantly correlated with the T2 relaxation times, but was positively correlated with the T2 ratio. @*Conclusions@#In patients with cervical radiculopathy, the SHINKEI-Quant technique can be used to quantitatively evaluate the compressed cervical nerve roots. The VAS score for upper arm pain was positively correlated with the T2 ratio. This suggests that the SHINKEI-Quant is a potential tool for the diagnosis of cervical nerve entrapment.

Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody

Methods@#This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. @*Results@#Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. @*Conclusions@#Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

Diffusion Tensor Imaging of the Spinal Canal in Quantitative Assessment of Patients with Lumbar Spinal Canal Stenosis

Methods@#Study participants comprised five healthy volunteers (mean age, 27.2 years) and 27 patients with LSS (mean age, 58.4 years) who were individually assessed using 3.0 Tesla magnetic resonance imaging. Intraspinal ADC and FA values of 10 intervertebral discs from healthy volunteers and 52 intervertebral discs from LSS patients were measured. Also, intraspinal canal area, Schizas classification (A: normal, B: mild stenosis, C: severe stenosis) and correlations with symptoms were investigated. Clinical symptoms were checked for the presence of low back pain (LBP), intermittent claudication (IMC), and bladder and bowel dysfunction (BBD). @*Results@#Compared to healthy individuals, LSS patients had significantly lower ADC (pppr=0.63, pp=−0.61, ppp<0.05) in patients with IMC or BBD. @*Conclusions@#Intraspinal DTI parameters such as ADC and FA values were associated with the Schizas classification, intraspinal canal area, and clinical symptoms, suggesting that ADC and FA may be useful for quantitative assessment of LSS.

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study

Purpose@#In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. @*Materials and Methods@#Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab. @*Results@#A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration;and a significant increase only observed in the lumbar spine. @*Conclusion@#Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.

Diffusion Tensor Imaging of the Spinal Canal in Quantitative Assessment of Patients with Lumbar Spinal Canal Stenosis

Methods@#Study participants comprised five healthy volunteers (mean age, 27.2 years) and 27 patients with LSS (mean age, 58.4 years) who were individually assessed using 3.0 Tesla magnetic resonance imaging. Intraspinal ADC and FA values of 10 intervertebral discs from healthy volunteers and 52 intervertebral discs from LSS patients were measured. Also, intraspinal canal area, Schizas classification (A: normal, B: mild stenosis, C: severe stenosis) and correlations with symptoms were investigated. Clinical symptoms were checked for the presence of low back pain (LBP), intermittent claudication (IMC), and bladder and bowel dysfunction (BBD). @*Results@#Compared to healthy individuals, LSS patients had significantly lower ADC (pppr=0.63, pp=−0.61, ppp<0.05) in patients with IMC or BBD. @*Conclusions@#Intraspinal DTI parameters such as ADC and FA values were associated with the Schizas classification, intraspinal canal area, and clinical symptoms, suggesting that ADC and FA may be useful for quantitative assessment of LSS.

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study

Purpose@#In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. @*Materials and Methods@#Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab. @*Results@#A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration;and a significant increase only observed in the lumbar spine. @*Conclusion@#Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.

Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection / Journal of Rural Medicine

Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in “rural” regions.Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan.Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events.Conclusion: G/P therapy is effective and safe for old-aged patients.

Effects of different obstacle height and movement pattern on supported leg sway during lateral stepping over in healthy young adults: Analysis using a small triaxial accelerometer / 体力科学

<p>The purpose of this study was to determine sway characteristics of a supported leg during a lateral stepping over obstacle task with different obstacle height and movement patterns, using a small triaxial accelerometer. We examined 20 healthy young adults to assess their trochanter malleolar distance traveled during a lateral stepping over obstacle task with obstacle heights of 30%, 50%, and 70%. The lateral stepping over tasks revealed flexion and extension patterns. We directed the subjects to grasp a forward handrail, perform the lateral step, and subsequently step over to the side. We calculated synthetic acceleration (SA) from acceleration data measured using two small triaxial accelerometers and two web cameras. We calculated supporting leg sway; RMS phases of X-, Y-, and Z-axes; and SA data. The subjects showed increased RMS of Y-axis and SA according to the obstacle height for the flexion pattern; however, they did not show change in RMS of Y-axis and SA according to the obstacle height for the extension pattern. During lateral stepping over, the RMS of Y-axis and SA for the flexion pattern were higher than for the extension pattern. The findings for the flexion pattern suggest that the center of gravity shifts higher according to increased obstacle height; consequently, the supporting leg becomes unstable. The findings for the extension pattern suggest that the “screw-home” rotation effect of the supporting leg during movement can support lateral stepping over better than the flexion pattern.</p>

Successful Treatment of Necrotizing Fasciitis and Toxic Shock Syndrome by Hip Amputation and Endotoxin Hemoadsorption / Journal of Rural Medicine

Background: Necrotizing fasciitis is a rare but severe condition associated with high mortality. We encountered a patient with severe and rapidly progressing necrotizing fasciitis. Patient: A 40-year-old male was hit by a tractor and received a wide laceration wound spanning the length of his posterior thigh. Soon after the accident, the wound was washed and debridement was performed. Two days postoperatively, we observed septic changes in the wound and diagnosed this condition as necrotizing fasciitis. Consequently, the patient's leg was amputated at the thigh. The patient, however, developed toxic shock syndrome after the amputation. Endotoxin adsorption using a polymyxin B-immobilized fiber column was performed for 2 days. Finally, a hip joint amputation was performed after 11 days, following which the patient's general condition gradually improved. Discussion: Treatment for necrotizing fasciitis should be initiated promptly. Early debridement is associated with a significant decrease in mortality. In severe conditions, endotoxin and cytokine removal by blood purification is one of the most effective treatments. Although group A streptococci are widely known as "flesh-eating bacteria," we should also consider a wide variety of pathogenic organisms to be the probable cause of severe necrotizing fasciitis. Conclusion: Management of necrotizing fasciitis requires careful investigation as well as an aggressive therapeutic approach, which may include urgent surgical intervention. In addition to surgery, endotoxin adsorption therapy should be considered.

Primary Care Pediatric Clinical Training in Middle-sized Community Hospital: Hoping to be a "Model Program" after the Obligation of Postgraduate Clinical Training / 医学教育

In Japan problems of the pediatric emergency-care system have recently increased the needs of consultation to deal with the growing anxiety of parents about how to raise their children and have decreased the number of pediatricians. We believe that one solution is to make pediatric primary care a required part of postgraduate clinical training and thereby increase the ability of nonpediatricians to provide pediatric primary care and to support the care of children. We hope that postgraduate clinical training programs will be reformed so that physicians of all departments can contribute to improving pediatric primary care.

Primary health care in a rural district, Akita prefecture / 日本農村医学会雑誌

Investigation was made into the health care conditions in a rural district in Akita Prefecture. Topographically, the district is divided into two parts-one characterized by mountain and the other by flat terrain.<BR>1. In remote, depopulated villages, per capita cost of public health is on the increase.<BR>2. The number of health personell, particularly public health nurses, is not enough to carry on various health programs.<BR>3. With the prospect of greater numbers of the aged in society, there is an urgent need for increased medical services along with the consolidation of primary health care. In order to meet the need, it is necessary to establish a regional community health system comprised of a hospital as a nucleus and neighborhood medical instituions such as clinics and health centers.

Health problems of women in mixed-farm households / 日本農村医学会雑誌

Investigations were made into the actual working and living conditions of adults, both men and women, in the families engaged in mixed farming.<BR>The working conditions were analyzed according to the types of crops farmers are growing. The work study was necessary to probe into the causes of farmers' health disturbances.<BR>A questionnaire revealed that farmers are short of sleep during the busiest season. Especially housewives are forced to cut down on their sleeping hours.<BR>It also found that some farmers spray pesticides in quantity and expose themselves to the potentially health injurious chemicals with alarming frequency.<BR>There was evidence to show that some ailments, notably low back pain, had been reduced due to imporovements on farmwork and working environment.<BR>Health checkups showed that the incidences of hypercholesterolemia and obesity remain high. There was imbalance between carolic intake and consumption.

Statistical Study on Urologic Patients for These 10 Years in Hiraka General Hospital / 日本農村医学会雑誌

The purpose of this report is to clarify urologic problems in rural districts. The number of patients who visited our clinic for these 10 years were 7, 313 as new outpatient and 1802 as inpatient. Three main diseases of rural area were acute inflammation of lower urinary tract, benign prostatic hypertrophy and lithiasis of upper urinary tract. Infection of lower urinary tract and aggravation of malignant tumors might be influenced by rural works and bad circumstances. Monthly distribution of patients was also under the influence of rural works.