[Efficacy and safety of transcatheter aortic valve replacement in the treatment of severe aortic stenosis].

Objective: To investigate the efficacy and safety of transcatheter aortic valve replacement (TAVR) in the treatment of severe aortic stenosis. Methods: The clinical data of patients with severe aortic stenosis who underwent TAVR at the People's Hospital of Xinjiang Uygur Autonomous Region between September 2016 and September 2022 were retrospectively analyzed. Changes in aortic transvalvular pressure gradients, valve orifice area, and activity tolerance of patients before and after the surgery were compared. Moreover, postoperative complications and follow-up results from 30 days to 6 years after the surgery were recorded. Results: A total of 76 patients were included in the study (50 males and 26 females), with an average age of (71.3±7.6) years, including 16 rheumatic valvular diseases, 60 senile degenerative diseases, 46 bicuspid valves and 30 tricuspid valves. The success rate of the operation was 96.1% (73/76). Compared with that before the operation, the mean aortic transvalvular pressure gradients decreased [(8.5±2.8) mmHg vs (68.5±19.2) mmHg (1 mmHg=0.133 kPa),P<0.001], but the valve orifice area increased [(1.91±0.31) cm2 vs (0.65±0.21) cm2, P<0.001]. Likewise, six-minute walking test (6MWT) showed that walking distance was longer after the surgery [(430±13) m vs (201±28) m, P<0.001]. There were 1 case of retroperitoneal hematoma, 1 case of stricture balloon dilatation after femoral artery suture concomitant with postoperative puncture site infection, 1 case of femoral artery surgical incision, 2 cases of valve-in-valve (ViV) and 5 cases of perivalvular leakage (4 cases were mild and 1 case was moderate) after the surgery, respectively. Moreover, acute left main artery occlusion during operation occurred in 1 case, ventricular rupture during operation occurred in 1 case and the patient was transferred to valve replacement surgery and finally dead, delayed coronary artery occlusion and death happened in 1 case, and all of the above-mentioned 3 cases were due to surgical failure. Postoperative pacemaker implantation due to third-degree atrioventricular block was performed in 5 cases. There were 1 case of pulmonary embolism, 1 case of transient right limb disorder, 1 case of gastrointestinal bleeding and 1 case of urethral bleeding after the surgery, respectively. The patients were followed up for (1.0±0.1) years (30 days to 6 years), and the results showed that 2 cases died, including 1 case died suddenly at home (the cause of death was unknown) and 1 case died of acute heart failure 8 months after the surgery. Chronic heart failure occurred repeatedly in 6 cases. The quality of life of other patients improved significantly. Conclusion: TAVR is effective and safe for patients with severe aortic stenosis.

Cooling ameliorates decreased milk protein metrics in heat-stressed lactating Holstein cows.

Cooling can alleviate the negative consequences of heat stress on multiple milk production metrics in dairy cows. However, it is still controversial whether cooling can increase milk protein content compared with heat-stressed cows. The objective of the present study was to evaluate the relief effect of cooling on the decrease in milk protein concentration during heat stress and elucidate the potential metabolic mechanisms. Thirty lactating multiparous Holstein cows (days in milk = 175 ± 25 d, milk yield = 27.5 ± 2.5 kg/d; mean ± SD) were assigned to 1 of 3 treatments: heat stress (HS; n = 10), cooling (CL; n = 10), and cooling with pair-feeding (PFCL; n = 10). The barns for PFCL and CL cows were equipped with sprinklers and fans, whereas the barn for HS cows were not. The average temperature-humidity index during the experiment ranged from 74 to 83. The spraying was activated automatically 2 times per day (1130-1330 h and 1500-1600 h) with 3 min on and 6 min off during the first 2 wk, and 1.5 min on and 3 min off during the last 2 wk, whereas the fans operated 24 h/d. The experiment lasted for 4 wk in total. Milk, urine, feces, total mixed ration, blood, and rumen fluid samples were collected weekly. Compared with HS, feed efficiency (1.24 and 1.49), milk protein yield (0.82 and 0.94 kg/d), and milk fat yield (0.98 and 1.26 kg/d) were increased in PFCL, whereas the differences between CL and HS were not significant. Compared with HS cows, PFCL and CL cows had a lower respiratory rate (70.6, 59.1, and 60.3 breaths per minute, respectively), rectal temperature (38.95, 38.61, and 38.51°C), and shoulder skin temperature (33.95, 33.25, 33.40°C), and had greater milk protein content (3.41, 3.72, and 3.69%) and milk fat percent (4.08, 4.97, 4.65%). Both the blood activity of catalase (increased by 12.8 and 41.0%) and glutathione peroxidase (12.6 and 40.4%) of PFCL and CL cows were greater than the HS cows. Compared with HS, cooling increased the blood content of glucose, methionine, threonine, and cystathionine by 10.7% and 10.3%, 19.0% and 9.5%, 15.8% and 12.0%, and 9.5% and 23.8% in PFCL and CL, respectively. In conclusion, the results indicated that cooling partially rescued milk protein synthesis induced by heat stress, and the potential mechanism may have been due to increased antioxidant ability, blood glucose, and key AA. Consequently, in addition to modifying the environment, nutritional and physiological strategies designed to influence carbohydrate, AA, and oxidative homeostasis may be an opportunity to maintain or correct low milk protein content during the warm summer months.

Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer.

Downregulation of cell division cycle-associated 3 (CDCA3) markedly inhibited cell growth and induced apoptosis in tumors. However, the effect of CDCA3 in pancreatic cancer (PAC) was rarely investigated. Therefore, this study attempted to clarify the role of CDCA3 in PAC. The mRNA and protein expression of CDCA3 were examined in PAC cell lines and tumor tissues by using real-time quantitative PCR (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). The effects of CDCA3 downregulation on cell proliferation, apoptosis, and colony information were investigated through MTT assay, Annexin V-APC single staining cell apoptosis detection, and colony formation test. The microarray and ingenuity pathway analysis were employed to explore the potential regulatory relation. The tumor xenograft model was established for determining the effect of CDCA3 downregulation on the growth of PAC in vivo. The results showed that the expression of CDCA3 in tumor tissues was higher than that of normal tissues (p<0.05). In addition, the mRNA expression of CDCA3 was markedly increased in PANC-1 cells and SW 1990 cells when compared with human pancreatic duct epithelial (HPDE) cells (p<0.05). MTT assay showed that the cell proliferation of PANC-1 cells and SW 1990 cells was significantly inhibited after the lentivirus transfection of CDCA3 knockdown (p<0.05). Annexin V-APC apoptosis assays suggested that the apoptotic cell number was markedly increased in the shCDCA3 group compared to that in the shCtrl group in SW 1990 cells and PANC-1 cells (p<0.05). Meanwhile, the activity of caspase-3/7 was obviously elevated in the shCDCA3 group compared to the shCtrl group (p<0.05). The colony formation was notably inhibited in the shCDCA3 group relative to the shCtrl group in SW 1990 cells (p<0.05). Moreover, the tumor growth was evidently suppressed in the shCDCA3 group compared with the shCtrl group in vivo (p<0.05). These findings revealed that CDCA3 plays a crucial role in the progress of PCA by regulating cell apoptosis and proliferation, which may serve as a potential target for PAC treatment.

[Effects of chronic intermittent hypoxia on blood pressure and vascular remodeling].

Objective: To investigate blood pressure and vascular remodeling of OSAS by establishing the chronic-intermittent hypoxia model in rat. Methods: Experiments were performed on 35 adult male Sprague-Dawley rats. Animals were randomly divided into four groups: unhandled control group (with 5 rats in it), CIH group at 9/6/3 weeks (with 10 ratsin each group). Rats in CIH group went through 8-hour intermittent hypoxia everyday, and those in control group were raising normally. After 9-week experiment, blood pressure was measured. The changes of the following indexes were observed: pathological changes of aorta and the middle aorta thickness (HE staining), the collagen of aorta wall (Masson staining). The experimental data were analyzed by SPSS 24.0 statistical software. The variance was analyzed by one-way analysis of variance, and the irregularity was selected using the calibration t test. Results: The systolic and diastolic blood pressures of the CIH9, 6, and 3 weeks groups and the control group were: (127±13) and (79±9), (124±11) and (81±7), (101±11) and (75±9), (91±10) and (65±9) mmHg (1 mmHg=0.133 kPa). The systolic blood pressure and diastolic blood pressure of the rats in the week of CIH 9 and 6 weeks were significantly higher than the control group (F=14.64, P=0.000; F=6.81, P=0.000). There was no significant difference in the mean blood pressure between the three groups of CIH and the control group. Membrane thickness in CIH9, 6 and 3 weeks and control group were: (20±2), (19±2), (14±2), (13±3) µm. Compared with the control group, the aortic pathology and thickness of the middle layer of the CIH9 and 6 weeks group were significantly thicker (F=20.24, P=0.000), but there was no significant difference between the CIH3 week group and the control group; the collagen deposition was unchanged compared with the control group. Conclusion: Intermittent hypoxia for 6 weeks or more in rats resulted in the increasement of blood pressure, morphological changes of aorta and vascular remodeling in thickened media.

Onset of Asian desertification by 22 Myr ago inferred from loess deposits in China.

The initial desertification in the Asian interior is thought to be one of the most prominent climate changes in the Northern Hemisphere during the Cenozoic era. But the dating of this transition is uncertain, partly because desert sediments are usually scattered, discontinuous and difficult to date. Here we report nearly continuous aeolian deposits covering the interval from 22 to 6.2 million years ago, on the basis of palaeomagnetic measurements and fossil evidence. A total of 231 visually definable aeolian layers occur as brownish loesses interbedded with reddish soils. This new evidence indicates that large source areas of aeolian dust and energetic winter monsoon winds to transport the material must have existed in the interior of Asia by the early Miocene epoch, at least 14 million years earlier than previously thought. Regional tectonic changes and ongoing global cooling are probable causes of these changes in aridity and circulation in Asia.

Earliest presence of humans in northeast Asia.

The timing of the earliest habitation and oldest stone technologies in different regions of the world remains a contentious topic in the study of human evolution. Here we contribute to this debate with detailed magnetostratigraphic results on two exposed parallel sections of lacustrine sediments at Xiaochangliang in the Nihewan Basin, north China; these results place stringent controls on the age of Palaeolithic stone artifacts that were originally reported over two decades ago. Our palaeomagnetic findings indicate that the artifact layer resides in a reverse polarity magnetozone bounded by the Olduvai and Jaramillo subchrons. Coupled with an estimated rate of sedimentation, these findings constrain the layer's age to roughly 1.36 million years ago. This result represents the age of the oldest known stone assemblage comprising recognizable types of Palaeolithic tool in east Asia, and the earliest definite occupation in this region as far north as 40 degrees N.

Colchicine treatment of the sciatic nerve reduces neurogenic extravasation, but does not affect nociceptive thresholds or collateral sprouting in neuropathic or normal rats.

The effect of topical colchicine treatment of the sciatic nerve on sciatic and saphenous nociceptive thresholds and neurogenic extra-vasation was investigated in normal and neuropathic rats. After a pilot investigation using several different concentrations of colchicine it was determined that treating the sciatic nerve with 5 mM colchicine did not usually affect the heat nociceptive threshold over the sciatic innervated plantar surface of the hindpaw. Mechanical nociception and motor function were also unchanged. Electrical stimulation of the sciatic nerve after intravenous injection of Evans blue dye causes extravasation of the dye in the cutaneous distribution of the nerve. The area and quantity of sciatic extravasation were measured 3 weeks after treating the sciatic nerve with colchicine. This treatment results in a marked loss of neurogenic extravasation, but there were no changes in the sciatic and saphenous mediated heat and mechanical nociceptive thresholds. The area of saphenous nociceptive innervation was mapped using pinch responses and saphenous neurogenic extravasation acutely after sciatic section. There was no change in the cutaneous distribution of saphenous nociceptive fibers when measured 3 weeks after the sciatic colchicine treatment. Some rats had their sciatic nerves transected immediately after colchicine treatment (5 and 50 mM) and the saphenous nociceptive thresholds and autotomy scores were followed postoperatively. Colchicine pretreatment of the sciatic nerve has no effect on the development of hyperalgesia or autotomy. Colchicine blocks axonal transport in peripheral nerve, including the orthograde transport of tachykinins, which probably explains its ability to induce prolonged reductions in sciatic neurogenic extravasation at concentrations that spare C-fiber nociceptor function. Sciatic nerve colchicine treatment does not trigger nociceptive fiber collateral sprouting from the adjacent saphenous nerve, nor does it influence the development of hyperalgesia and autotomy behavior after sciatic transection.

Pseudoxanthoma elasticum. A report of 5 cases in one family.

Five cases of pseudoxanthoma elasticum (PXE) found in one family are reported. The hereditary pattern is probably of autosomal dominant type 2. In the fundi of all the 5 cases, mottlings of the retinal pigment epithelium or orange skin-like lesions in both eyes which are of significant diagnostic importance are seen. The fundus changes are more prominent when skin lesions are typical. Under electron and light microscope, the pathological changes of clinically typical and atypical lesions show similar characteristics of this disorder. Remarkable calcification of elastic fibers with abnormal contour and fragmentation, destruction of mitochondria of fibroblasts and a great number of mast cells leaning against fibroblasts are the chief findings in the histochemically stained specimens. The pathogenetic mechanism of this disorder is possibly dystrophy of elastic fibers with its inherent nature of being easily calcified. Involvement of autoimmune factors in the pathogenesis is quite possible.

A family with Fabry's disease. Ocular manifestations and transmission electron microscopic examination of a skin lesion biopsy.

A family with Fabry's disease including 2 hemizygotes and 3 heterozygotes is reported. The ocular manifestations include tortuosity of conjunctival vessels, Fabry's deposits underlying the anterior capsule of the lens and the whorl-like corneal dystrophy. Foam cells or mulberry cells in the urinary sediment and varying numbers of high electron-dense inclusions in the cytoplasm of endothelial cells in skin lesions are also important in diagnosing this disease. The concentrations of lipid peroxide in the sera of 2 hemizygotes in this report were higher than normal, possibly due to the patients weak ability of anti-oxygenation and malfunction of cells whose plasma membranes are easily attacked by free oxygen radicals. The biochemical and pathological changes, diagnosis, treatment, genetics and prevention of the disease are discussed.