BMAL1-TTK-H2Bub1 loop deficiency contributes to impaired BM-MSC-mediated bone formation in senile osteoporosis.

During the aging process, the reduced osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) results in decreased bone formation, which contributes to senile osteoporosis. Previous studies have confirmed that interrupted circadian rhythm plays an indispensable role in age-related disease. However, the mechanism underlying the impaired osteogenic differentiation of BM-MSCs during aging and its relationship with interrupted circadian rhythm remains unclear. In this study, we confirmed that the circadian rhythm was interrupted in aging mouse skeletal systems. The level of the core rhythm component BMAL1 but not that of CLOCK in the osteoblast lineage was decreased in senile osteoporotic specimens from both human and mouse. BMAL1 targeted TTK as a circadian-controlled gene to phosphorylate MDM2 and regulate H2Bub1 level, while H2Bub1 in turn regulated the expression of BMAL1. The osteogenic capacity of BM-MSCs was maintained by a positive loop formed by BMAL1-TTK-MDM2-H2Bub1. Furthermore, we demonstrated that using bone-targeting recombinant adeno-associated virus 9 (rAAV9) to enhance Bmal1 or Ttk might have a therapeutic effect on senile osteoporosis and delays bone repair in aging mice. In summary, our study indicated that targeting the BMAL1-TTK-MDM2-H2Bub1 axis via bone-targeting rAAV9 might be a promising strategy for the treatment of senile osteoporosis.

Abiraterone combined with prednisone in the treatment of high-risk high-tumor load metastatic castration-resistant prostate cancer: a case report and literature review / 现代泌尿外科杂志

【Objective】 To observe the efficacy of abiraterone (AA) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). 【Methods】 The clinical data of a newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) patient with high risk and high tumor load were analyzed. After operation and endocrine therapy, the disease evolution was observed. Relevant literature was reviewed. 【Results】 After laparoscopic radical prostatectomy, 6-month bicalutamide and androgen deprivation therapy (ADT), the total prostate specific antigen (tPSA) was reduced to the lowest of 0.51 ng/mL, and then increased month by month. After domestic abiraterone (trade name: Qingkeshu) in the 8th month was administered for 4 months, tPSA continued to increase to 12.39 ng/mL. The case was then diagnosed as mCRPC. The treatment was adjusted again in the 11th mouth and the patient received AA (trade name: Zeke) combined with prednisone and ADT, and tPSA decreased to 0.17 ng/mL 2 months later. After 14 months of treatment, tPSA remained at about 0.12 ng/mL. Systemic ECT examination indicated that the range of bone metastases decreased and some areas of nuclide concentration turned shallow without obvious adverse reactions. 【Conclusion】 AA combined with prednisone and ADT can produce rapid decline in PSA and a good response in mCRPC patients. It can also significantly slow the progression of bone metastasis and relieve pain symptoms without obvious adverse reactions. Long-term efficacy needs further observation.

Clinical value of peripheral blood circulating tumor cells in the diagnosis and treatment of prostate cancer / 中国基层医药

Objective:To investigate the clinical value of peripheral blood circulating tumor cells (CTC) in the diagnosis and treatment of prostate cancer.Methods:Sixty-four patients with prostate cancer who received treatment in Xinjiang Production and Construction Corps Hospital, China between June 2018 and May 2020 were included in the cancer group. An additional 35 patients with benign prostatic lesions who concurrently received treatment in the same hospital were included in the benign disease group. Twenty male patients with non-prostate disease were included in the control group. Cell enrichment, separation, staining and identification together with Gleason score and pathological stage were subjected to one-way analysis of variance.Results:The percentage of patients with CTC count ≥ 3 in the cancer, benign disease and control groups was 73.43% (47/64), 17.14% (6/35) and 10.00% (2/20), respectively. The level of prostate-specific antigen in patients with CTC was significantly higher than that in patients without CTC ( t = 2.89, P < 0.05). There was significant difference in CTC count between different Gleason score groups ( F = 3.25, P < 0.05) and between different pathological stage groups ( F = 3.42, P < 0.05). Conclusion:Peripheral blood CTC measurement can be used as an auxiliary method for the differentiation of benign and malignant prostate diseases. CTC count in patients with prostate cancer is correlated with prostate-specific antigen level, Gleason score, and pathological stage. Therefore, peripheral blood CTC measurement plays an auxiliary role in predicting prognosis in patients with CTC. This study is innovative and scientific.

Follow-up study on long-term therapeutic effect of structured patient education and exercise therapy on knee osteoarthritis / 中华骨科杂志

Objective:To evaluate the long-term effect of structured patient education and exercise therapy for knee osteoarthritis (KOA).Methods:Prospective cohort study, 162 patients with KOA were consecutively recruited from May 2016 to December 2019 to receive structured patient education and exercise therapy and were followed up 3 years after the recruitment. All the patients received two 1-hour educational courses and exercise therapy twice per week for six weeks under the supervision of physicians or physical therapists. Knee injury and osteoarthritis score (KOOS), visual analog score of pain (VAS), intermittent and constant OA pain (ICOAP), self-efficacy for arthritis were queried at 3-month and 36-month follow-up visit. We fitted linear mixed-effects models to examine the difference in scores between baseline and 3-month and 36-month visits.Results:109(67.3%) patients finished both 3-month and 36-month follow-up visits. The KOOS pain score increased from 70.8±1.7 at baseline to 79.7±1.8 at 36 months ( P<0.05). The KOOS symptom score increased from 66.8±2.0 at baseline to 74.9±2.1 at 36 months ( P<0.05). The KOOS daily function score increased from 81.7±1.4 at baseline to 87.0±1.5 at 36 months ( P<0.05). KOOS motor function score increased from 47.4±2.8 at baseline to 55.0±2.9 at 36 months ( P<0.05). The quality of life score of KOOS increased from 46.6±2.1 at baseline to 63.5±2.2 at 36 months ( P<0.05). Compared with the baseline data, there were statistically significant improvements in all subscales of KOOS in 36 months after exercise therapy intervention ( F=14.548, 8.102, 11.394, 5.687 and25.942, P<0.05). VAS pain score of left knee, VAS pain score of right knee, ICOAP score, self-efficacy pain score and other symptoms were also significantly improved ( F=17.643, 26.791, 8.290, 4.052 and 3.654, P<0.05). Conclusion:Structured patient education and exercise therapy are effective in improving knee pain and function as well as self-efficacy until as long as 36 months.

Correlations between the sagittal plane parameters of the spine and pelvis and lumbar disc degeneration.

BACKGROUND: Studies have shown that lumbar disc herniation, degenerative lumbar instability, and other degenerative lumbar spinal diseases are often secondary to disc degeneration. By studying the intervertebral disc, researchers have clarified the pathological changes involved in intervertebral disc degeneration but have ignored the roles of biomechanical factors in the development of disc degeneration. This study aims to investigate the relationships among the location, scope, and extent of lumbar disc degeneration and sagittal spinal-pelvic parameters. METHODS: A retrospective analysis was performed on the clinical data of 284 patients with lumbar degenerative disc diseases (lumbar disc herniation and degenerative lumbar instability) from January 2013 to December 2016. Statistics were calculated for the following: (1.) patients' general information: name, sex, age, height, and weight. (2.) Measurements of sagittal parameters from total spinal radiographs: thoracic kyphosis (TK), Lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), T1 tilt angle (TA), and T1 pelvic angle (TPA). (3.) Location, scope, extent, and overall degree of lumbar disc degeneration. Parameters were analyzed in groups by sex, PI, and SVA, and a correlation analysis was performed for the location, scope, extent, and overall degree of lumbar intervertebral disc degeneration with 8 spinal-pelvic sagittal parameters. RESULTS: The mean ages of the male and female patient groups were 59.00 and 53.28 years old, respectively (P < 0.05). The PT, location, scope, and overall degree of degradation were significantly different between the sexes (P < 0.05). Linear correlation analysis results showed that the overall degree and extent of degradation (r = 0.788, P < 0.01), LL and SS (r = 0.737, P < 0.01), PI and PT (r = 0.607, P < 0.01), and TPA and PT (r = 0.899, P < 0.01) were strongly correlated. The location values were 4.08 ± 0.72 in patients with PI≤50° and 3.62 ± 0.94 in patients with PI> 50° (P = 0.018). Different SVASVA groups differed in their overall degree of degeneration (P = 0.002). CONCLUSIONS: The location of lumbar intervertebral disc degeneration is affected by spinal-pelvic sagittal morphology. Populations with small PI values tend to exhibit degeneration at the L4/5 and L5/S1 discs, and populations with large PI values tend to exhibit degeneration at the L3/4 and L4/5 discs. The SVA value and the overall degree of lumbar disc degeneration are positively correlated.

Research progress of drugs in treatment of stress gastric ulcer / 医学研究生学报

The stress gastric ulcer is due to a stress-induced gastric erosions, superficial ulcers and bleeding gastric mucosal le-sions characterized by stress. Its etiology is closely associated with lives, the incidence is increasing. In recent years, the the basic re-search of drugs focuses on inhibition of oxidative damage caused by stress, anti-inflammatory cytokine expression, and regulation of gastric acid, etc., and made a lot of success. Treatment choice of stress ulcer drug gradually increased. The effects of plant extracts on stress ul-cer get more and more attention. This article reviews research progress of the treatment drugs of stress ulcer in the current stage.

THE SURFACE STRUCTURE OF THE PINEAL RECESS IN RAT:A SCANNING ELECTRON MICROSCOPE STUDY / 解剖学报

The surface structure of the pineal recess in rat (Sprague-Dawley) was observedby using scanning electron microscope.Because of the distribution ofthe cilia and microvilli shows a regular changes from peripheralarea to central area in the recess,the surface of the recess can be divided intoperipheral,transitional and central zone.In the peripheral zone,there aresupraependymal cells in different appearance among those tufted cilia.Thetransitional zone is between peripheral and central zone.The cilia in this zone arefewer than those of the peripheral zone.We have observed the neuron-like suprae-pendymal cell with a splndle shaped cell body and numerous small holes as well assupraependymal nerve fibers in the floor of this zone.The ending of the nerve fiberis varicose.Some smooth areas devoid of cilia and microvilli were presentin the central zone.There are also neuron like cells with slender processes,roundsupraependymal cell,some fine crisscrossing fibers and some sprouted cilia.Acluster of bleb-like structures are present in this zone.The relations between thesurface of the recess and the pineal gland are discussed.

THE CONNECTIONS OF THE VISUAL PORTION OF THE THALAMIC RETICULAR NUCLEUS IN GOLDEN HAMSTERS / 解剖学报

The thalamic reticular nucleus (RT) is a sheet-like nucleus which surrounds the anterolateral aspect of the dorsal thalamus. In this study, we present data on the connections of the dorsocaudal portion of the RT in hamsters using anterograde, retrograde and transneuroual fiber tracing techniques. After injection of one eye with a mixture of ~3H-proline and ~3H-fucose (2 animals; 10 and 15 days survival time), transneuronal label was located in the dorsocaudal portion of the RT (dc RT) on both sides of the thalamus.After separate injection of horseradish peroxidase (HRP) into the thalamic lateral posterior nucleus (LP), dorsal and ventral nuclei of the lateral geniculate body (LGd, LGv) (8 animals, one day survival time), HRP labelled neurons wereobserved in the dorsal, middle and ventral area of the ipsilateral dc RT respectively.A small iontophoretic injection of a mixture of ~3H-proline and ~3H-leucine was made into different sites of area 17 in each of 3 hamsters (one day survival time),in each case an elongated patch of label was located in nearly the entire rostrocaudal extent of the ipsilateral dc RT. A caudal Injection in area 17 resulted in labelling the dorsal area while a progressively more rostral injection resulted in labelling a more ventral area of the dc RT.Thus, the dorsocaudal portion of the RT can be defined as the visual portion of the nucleus because it has connections with many of the known visual centres, namely, the visual cortex, LP, LGd, LGv Furthermore, because of the topographic connection with area 17 and the visual thalamic nuclei, the notion that the dc RT as a nucleus which is capable of processing specific and localised visual information. should be considered.

DISTRIBUTION AND MORPHOLOGIC CHARACTERISTICS OF ACETYCHOLINESTERASE——CONTAINING NEURONS IN THE RAT BRAIN / 解剖学报

Distribution and morphologic features of AChE-containing neurons were observed by the technique of AChE regeneration. There are three kinds: AChE-staining cells--heavily stained cells, medium stained cells and lightly stained cells. Most heavily stained cells are larger multipolar cells. They are located mainly in striatum, basal forebrain, hypothalamus, substantia nigra, locus coeruleus, red nucleus, ventral tegmental nucleus, parabrachial nucleus, pontine tegmental nucleus and the motor nuclei of cranial nerves. The results of AChE-staining were compared with the date of ChAT immunohistochemistry. The relationship between AChE and cholinergic neurons as well as the nature of AChE-containing neurons were discussed.