Objective:To study the effects of Zuogui Pills on the expressions of miR-133b-3p and RhoA in osteoclasts of postmenopausal osteoporosis rats; To discuss its potential mechanism.Methods:SD female rats were randomly divided into normal group, model group, sham-operation group, and Zuogui Pills group using a random number table method, with 6 rats in each group. The model group and Zuogui Pills group were treated with oophorectomy to construct a rat model of osteoporosis. Zuogui Pills group was orally administered with Zuogui Pills decoction at a concentration of 10 g/kg for 12 consecutive weeks. Colorimetric method was used to measure the serum calcium and phosphorus levels of rats, and ELISA method was used to detect ALP levels. Bone density meter was used to measure the bone density of the femurs of rats in each group. The osteoclast of each group were cultured, and the expressions of RANKL and RUNX2 protein were detected by Western blot. MiRNA sequencing and differential expression analysis were performed on bone tissues of rats. Osteoclasts were treated with miR-133b-3p mimic and its negative control. The cell proliferation activity of osteoclasts was detected by cell counting kit-8 (CCK-8). The osteoclast differentiation activity was detected by the tartrate-resistant acid phosphatase staining. The dual-luciferase reporter assay was used to detect the relationship between miR-133b-3p and RhoA. The "rescue" experiment of miR-133b-3p mimic and RhoA co-expression were used to study the molecular regulatory mechanism of Zuogui Pills on osteoclast activity.Results:Compared with the model group, the bone mineral density of Zuogui Pills group significantly increased ( P<0.05, P<0.01), the levels of calcium and phosphorus in serum increased, the level of alkaline phosphatase ALP decreased ( P<0.05), the expression of RANKL protein decreased, and the expression of RUNX2 protein increased. Sequencing results showed that rno-miR-133b-3p was down-regulated in osteoclasts of postmenopausa osteoporosis rats treated with Zuogui Pills with the maximum difference ( P<0.01). Q-PCR results showed that the expression of miR-133b-3p in osteoclasts of Zuogui Pills group was significantly lower than that of the model group. The upregulation of miR-133b-3p could significantly promote the cell proliferation and differentiation of osteoclasts. RhoA overexpression could reverse the excessive proliferation and differentiation of osteoclasts caused by miR-133b-3p overexpression. Conclusions:RhoA is the target gene regulated by miR-133b-3p. Zuogui Pills can inhibit the activity of osteoclasts by regulating miR-133b-3p/RhoA axis, relieving the symptoms of osteoporosis.

OBJECTIVE To explore the effects of pterostilbene （PTE） on wound healing in diabetic skin ulcer model rats and its mechanism. METHODS Ten SD rats were grouped into control group； after diabetic skin ulcer model of other rats was induced by giving high-fat and high-sugar diet+intraperitoneal injection of streptozotocin+cutting off the skin and subcutaneous tissue in the marked area of the back， model rats were randomly divided into model group， PTE low-dose group （40 mg/kg）， PTE high-dose group （80 mg/kg）， PTE high-dose+PP2 group （80 mg/kg PTE+2 mg/kg SRC inhibitor PP2）， with 10 rats in each group. On the second day after modeling， the rats in each drug group were intraperitoneally injected with corresponding drug solutions， while the rats in control group and model group were intraperitoneally injected with normal saline， once a day， for 14 consecutive days. The wound healing rate of rats in each group was measured on the 7th and 14th day of administration； the contents of interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α） and vascular endothelial growth factor （VEGF） in the serum of rats were detected； the pathological changes of wound granulation tissue were observed， and the expressions of SRC/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway-related proteins in wound granulation tissue were detected. RESULTS Compared with control group， the wound healing rate， serum content of VEGF， the phosphorylation levels of SRC， MEK1/2 and ERK1/2 were decreased significantly （P＜0.05）， while serum contents of IL- 1β， IL-6 and TNF-α were increased significantly （P＜0.05）； there was obvious infiltration of inflammatory cells in the wound granulation tissue， and the number of new blood vessels decreased. Compared with model group， above indexes of PTE low-dose and high-dose groups were improved significantly （P＜0.05）， and the pathological injury of granulation tissue in wound was improved. PP2 significantly reversed the improvement effects of PTE on the above indexes （P＜0.05）. CONCLUSIONS PTE can promote the wound healing of diabetic skin ulcer model rats， the mechanism of which may be related to activating SRC/MEK/ERK signaling pathway.

BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Aged ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Arteries ; Atrophy ; Brain/metabolism* ; Cerebral Cortex/metabolism* ; Cerebrovascular Circulation ; Constriction, Pathologic/pathology* ; Female ; Humans ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Positron-Emission Tomography/methods*

Keratitis-ichthyosis-deafness (KID) syndrome has genetic heterogeneity, and the clinical manifestations of some patients may overlap with Clouston syndrome. A 34-year-old female patient came to our department with a complain of “sparse hair, rough skin, photophobia and deafness for more than 30 years.” We found that the proband and two other family members (57-year-old mother and 4-year-old daughter) had similar clinical manifestations:systemic hair loss, generalized skin hyperkeratosis, especially in the metacarpophalangeal area. Subungual hyperkeratosis, finger/toenail dystrophy, as well as photophobia and epiphora. According to the investigation, one of the family members also had similar clinical manifestations (grandfather of the proband) and he’s died. The other three members of the family had no hearing impairment, and all patients had typical nail dystrophy, hair loss and palmoplantar hyperkeratosis, similar like as seen in Clouston syndrome, so we suspected to diagnose the case as Clouston syndrome. However, after genetic testing, it was found that the proband, his mother and daughter all had p.Asp50Asn heterozygous mutations in the GJB2 gene, and no mutation was detected in GJB6. The modified diagnosis was KID syndrome.

After more than 100 years of development， spray drying technology has become more mature and widely used， and it is of great importance in the field of traditional Chinese medicine （TCM）. TCM powders prepared by spray drying is the raw material of dispensing granules， and the powder properties have an important influence on subsequent molding process and product quality. As a new form of TCM， dispensing granules have been included in the management category of TCM decoction pieces， indicating a broader application market， and a consensus has also been reached on the importance of TCM powder research. Based on this， the author summarized the application progress of spray drying in the study of TCM powders， including the factors affecting spray drying process， such as liquid properties， process parameters and equipment factors， as well as the application of computational fluid dynamics （CFD） and thermodynamic model in spray drying process simulation. Moreover， some commonly used pharmaceutical excipients for the modification of TCM powders were also introduced such as maltodextrin， microcrystalline cellulose and povidone. In addition， spray drying technology can also be used as a preparation technology for new drug delivery systems such as microcapsules and solid dispersions. Through the summary of this paper， the author suggests that the future research direction of spray drying of TCM can be carried out from the aspects of application rule of the coprocessing auxiliary materials based on the "unification of medicines and excipients"， the "structure-property" relationship of spray-dried powders and the application of computer simulation and design， so as to further enrich the application of spray drying in the field of TCM powders.

Objective To explore the clinical and imaging efficacies of stent-assisted embolization and flow diversion in the treatment of intracranial aneurysms ≥10 mm. Methods Eighty-six patients with intracranial aneurysms≥10 mm, admitted to our hospital from January 2012 and February 2018, were chosen in our study; all 22 patients with ruptured aneurysms accepted stent-assisted embolization. Singular stent-assisted embolization was used in 55 patients, multiple stent-assisted embolization was used in 18 patients, and flow diversion was used in 13 patients. The immediate postoperative complete occlusion rate, complication incidence, and clinical and imaging follow-up data were retrospectively analyzed. Results (1) Results of immediate postoperative complete occlusion:Raymond grading I was noted in 56 patients, grading II in 6 patients, and grading III in 24 patients. Significant differences on immediate postoperative complete occlusion rates were noted among the three group (P<0.05); one patient had intra-stent thrombosis in the patients from singular stent-assisted embolization group, one patient with middle cerebral artery aneurysm had contralateral muscular dysplasia resulted from perforator occlusion and one patient with basal aneurysm had dysarthria resulted from perforator lesion in the patients from multiple stent-assisted embolization group; no perioperative complication was noted in patients from flow diversion group. (2) The prognosis of 86 patients was good;imaging follow-up results showed that 32 patients had occlusion, 7 had neck residue and 16 had recurrence in the singular stent-assisted embolization group; 11 patients had occlusion, one had neck residue and 6 had recurrence in the multiple stent-assisted embolization group; 11 patients had occlusion and 2 had neck residue in the flow diversion group; there were no statistically significant differences in follow-up results of aneurysms among the three groups (P>0.05). Conclusion Both flow diversion and stent-assisted embolization are effective methods for treatment of intracranial aneurysms≥10 mm.

Objective To investigate the effect of α7nAchR gene 713T>C mutation on the cognitive function and Aβ expression in Alzheimer′s disease(AD)mice.Methods Twenty APPSwe transgenic APPa7KO mice(6 months old,α7nAchR gene knockout)were divided into the mutation type group and wild type group according to the random number table method,10 cases in each group.The mutation type and wild type of AVV-α7nAchR cDNA were respectively injected by lateral ventricle,once per month,for 6 times.The change of cognitive function in mice was examined by Morris water maze.The ELISA method was used to detect Aβ 40 and Aβ 42 expression levels.The Aβ plaque deposit situation was detected by the immunochemical method.Results Compared with the mice in the wild type group,the escape latency and the time of first time to find the platform of the mice in the mutation type group were significantly extended,while Hippocampal Aβ40 and Aβ42 expression levels were significantly increased,the difference was statistically significant(P＜0.05).Conclusion α7nAchR gene 713T>C mutation aggravates the cognitive function impairments in AD mice and hippocampal neuron Aβ expression level.

BACKGROUNDOccult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP.

METHODSA total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed.

RESULTSOf the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence.

CONCLUSIONSPerioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.

Adult ; Cervical Intraepithelial Neoplasia ; Combined Modality Therapy ; Female ; Humans ; Hysterectomy ; Lymph Node Excision ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Unknown Primary ; Postoperative Complications ; Retrospective Studies ; Risk Factors ; Uterine Cervical Neoplasms

Gastrodia elatais graded as top medication in theShen Nong’s Herbal Classic. It was mainly distributed in southwest China. Its quality varied with geographical location. And the quality difference between wild and cultivated sample was extreme. Identifications using traditional methods were unable to accurately distinguish the quality ofG. elata. Therefore, near-infrared (NIR) spectroscopy combined with pattern recognition method was used to distinguish the quality ofG. elata from different geographical locations as well as cultivated or wild. The results demonstrated that using NIR spectroscopy combined with multiclass classification algorithm, the geographical location ofG. elata can be accurately distinguished. The prediction accuracy can reach as high as 94.3% and 96.4% for both applications. Besides, the classification model was built without preprocessing; hence, it can be extended to be applied on-site.