OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1， ginsenoside Re， ginsenoside Rb1， tenuifolin， polygalaxanthone Ⅲ and 3， 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times， extraction duration， and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes， analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently， process optimization and validation were conducted by integrating grey relational analysis （GRA） and back propagation （BP） neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two， extracting 3 times，extracting for 1 h each time； the average comprehensive score of the validation experiment was 91.10 （RSD＝0.31%， n＝3）. The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time， extracting for 1.5 h each time； the average comprehensive score of the validation experiment was 95.89 （RSD＝0.73%， n＝3）. Considering practical production requirements， the optimal water extraction technology was extraction performed three times， with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions， with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.

OBJECTIVE: To compare the effectiveness and shoulder function of reverse total shoulder arthroplasty (RTSA) and open reduction and internal fixation (ORIF) in the treatment of Neer three/four-part proximal humeral fractures in the elderly. METHODS: Randomized controlled analysis was conducted on 68 patients over 70 years old with Neer three/four-part proximal humeral fractures treated with RTSA or ORIF between January 2020 and June 2022. The patients were randomly divided into RTSA group ( n=32) and ORIF group ( n=36). There was no significant difference ( P>0.05) in the baseline data such as age, gender, body mass index, injured side, Neer classification, and preoperative Charlson comorbidity index, visual analogue scale (VAS) score, Constant shoulder score, Oxford shoulder score (OSS), and hemoglobin (Hb). The operation time, intraoperative blood loss, reduction of Hb on the 3rd day after operation, hospital stay, total cost of hospitalization, complication incidence, range of motion of shoulder joint at 2 years after operation, VAS score before operation and at 5 days and 1 month after operation, Constant shoulder score and OSS score before operation and at 2 years after operation, and imaging results during follow-up were recorded and compared between the two groups. RESULTS: Compared with the ORIF group, the RTSA group had longer operation time, less intraoperative blood loss, and higher total cost of hospitalization ( P<0.05). There was no significant difference in Hb reduction on the 3rd day after operation between the two groups ( P>0.05). The VAS scores significantly improved in both groups at 5 days and 1 month after operation ( P<0.05), but there was no significant difference between the two groups ( P>0.05). All patients were followed up 26-35 months, with an average of 31.2 months. In the RTSA group, there were 2 cases of poor healing of superficial incision and 1 case of transient nerve injury. There was no complication such as bone resorption around the prosthesis, lucent band, prosthesis loosening, or periprosthetic fracture in all patients. In the ORIF group, there was 1 case of poor healing of superficial incision, 3 cases of nonunion of fracture, 1 case of arthritis secondary to humeral head necrosis, and 1 case of bone absorption of large tuberosity, and no displacement or fracture failure of internal fixation was found in all patients. There was no significant difference in the incidence of complications [9.4% (3/32) vs 16.7% (6/36)] between the two groups [ OR (95% CI): 0.828 (0.171, 4.014), P=0.814]. In the RTSA group, 28 cases were graded 0 and 4 cases were graded 1 at 2 years after operation. Constant and OSS scores of RTSA group were significantly better than those of ORIF group ( P<0.05). The Constant score was significantly better than ORIF group in activity and strength, range of motion, lifting, abduction, and external rotation ( P<0.05), and there was no significant difference in pain, daily function, and internal rotation between the two groups ( P>0.05). The RTSA group had a significantly greater range of motion in lifting, abduction, and external rotation than ORIF group ( P<0.05), but there was no significant difference in internal rotation between the two groups ( P>0.05). CONCLUSION Application of RTSA as the initial treatment of Neer three/four-part proximal humeral fractures in the elderly can achieve better rehabilitation of joint activity and lower risk of early reoperation, and improve the quality of life of elderly fracture patients. However, the difficulty of revision and the high cost of treatment require the surgeon to pay full attention and strictly grasp the indications.
Humans ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Shoulder Fractures/surgery* ; Arthroplasty, Replacement, Shoulder/methods* ; Aged ; Bone Plates ; Open Fracture Reduction/methods* ; Range of Motion, Articular ; Treatment Outcome ; Shoulder Joint/physiopathology* ; Aged, 80 and over ; Operative Time ; Postoperative Complications/epidemiology* ; Length of Stay

Objective:To screen the differentially expressed exosomal miRNAs derived from liver cancer stem cells (LCSCs) and its effect on the malignant biological characteristics of liver cancer cells.Methods:miRNA expression profile chip was used to analyze the differentially expressed exosomal miRNA derived from LCSCs. The effects of miRNA on malignant phenotypes of LCSCs were identified. The cells were further treated with doxorubicin at different concentrations (0, 150, 300 μmol/L), and the expression level of miR-196a was detected by quantitative real-time PCR (qRT-PCR). The apoptosis of liver cancer cells cultured by exosomes derived from LCSCs (Exo-NC group) and exosomes derived from miR-196a inhibited LCSCs (Exo-Inhibitor group) and the activity of caspase3/7 under the action of exosomes from LCSCs were detected. Nude mice were randomly divided into Do-PBS group, Do-Exo-Inhibitor group and Do-Exo-NC group using random number table method, with 5 mice in each group, and the effect of miR-196a on nude mice xenograft tumor model with liver cancer cells was analyzed.Results:In this study, exosomes were isolated and purified from CD133 + Huh7 stem cell culture supernatant. miR-7162-3p, miR-1910-5, miR-3613-3p, miR-196a and miR-155-5p were up-regulated, while miR-1246 and miR-3613-5p were down-regulated. miR-7162-3p, miR-196a and miR-155-5p in exosomes had important effects on the self-renewal ability of LCSCs. miR-1910-5p, miR-196a and miR-155-5p had important effects on the invasion ability of liver cancer stem cells, among which miR-196a had the most significant inhibitory effect. Treatment for 24 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin was 0.96±0.05, 1.23±0.05 and 2.33±0.03 respectively, with a statistically significant difference ( F=996.90, P<0.001). Treatment for 48 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin were 1.02±0.07, 2.35±0.05 and 2.89±0.55 respectively, with a statistically significant difference ( F=303.00, P<0.001). When the concentration of doxorubicin was 0 and 300 μmol/L, the apoptosis rates of the Exo-NC group were 9.37%±0.19% and 11.64%±0.27%, and those of the Exo-Inhibitor group were were 18.80%±1.91% and 22.79%±1.57%, with statistically significant differences ( t=4.41, P=0.048; t=4.96, P=0.038). When doxorubicin was not used, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.94±0.08 and 0.97±0.09, and those in the Exo-Inhibitor group were 1.56±0.01 and 1.58±0.01, with statistically significant differences ( t=11.41, P=0.008; t=6.07, P=0.026). Under 300 μmol/L doxorubicin, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.95±0.07 and 1.36±0.08, and those in the Exo-Inhibitor group were 2.84±0.08 and 3.20±0.14, with statistically significant differences ( t=24.20, P=0.002; t=15.78, P=0.004). The results of xenograft tumor in nude mice showed that the tumor volumes of Do-PBS, Do-Exo-Inhibitor and Do-Exo-NC groups increased successively, which were (1 051.86±89.90) mm 3, (1 310.91±86.66) mm 3 and (2 185.14± 352.34) mm 3 respectively, with a statistically significant difference ( F=30.28, P<0.001). The weights of the transplanted tumors in the 3 groups increased successively, which were (0.36±0.10) g, (0.39±0.12) g and (0.76±0.16) g respectively, with a statistically significant difference ( F=11.81, P=0.002). The expression of miR-196a in tumors was significantly decreased after miR-196a inhibitor transfection. The expression levels of the 3 groups were 1.05±0.16, 0.38±0.08 and 2.17±0.26, with a statistically significant difference ( F=48.93, P<0.001). Conclusion:The exosomal secreted by LCSCs can enhance the resistance of liver cancer cells to doxorubicin by miR-196a.

Objective:To investigate the effect and mechanism of miR-451 on the proliferation and migration of human colorectal cancer cell SW480 by targeting macrophage migration inhibitory factor (MIF).Methods:Microarray analysis was used to screen differentially expressed microRNAs and messenger RNA in SW480 cells. Real-time quantitative PCR (RT-qPCR) was used to detect the expressions of miR-451 and MIF in SW480 cells before and after transfection. Cell clone formation assay and Transwell assay were used to detect the proliferation and invasion of SW480 cells, respectively. Cell scratch assay was used to detect the migration ability of SW480 cells. The TargetScan database was used to analyze the correlation between miR-451 and MIF. Dual luciferase reporter gene was used to detect the interaction of miR-451 and MIF. MTT assay was used to detect the viability of SW480 cells.Results:Compared with human normal colorectal mucosal cell FHC (1.00), the expression of miR-451 was down-regulated in SW480 cells ( 0.36±0.18, P<0.001). Knockdown of miR-451 promoted proliferation, and migration of SW480 cells. Compared with that in FHC cells, MIF expression was up-regulated in SW480 cells (2.28±0.45, P<0.001). MIF down-regulation inhibited SW480 cell proliferation, invasion and migration. MiR-451 specifically bind to the MIF 3′UTR and regulated the expression of MIF. Overexpression of miR-451 reduced while overexpression of MIF increased the viability of SW480 cells. Overexpression of MIF promoted the proliferation and migration of SW480 cells ( P<0.01), reversed the effect of miR-451 suppressed proliferation and migration of SW480 cells. Conclusion:MiR-451 may regulate proliferation and migration of human colorectal cancer cells by targeting MIF.

Objective:To investigate the effect and mechanism of miR-451 on the proliferation and migration of human colorectal cancer cell SW480 by targeting macrophage migration inhibitory factor (MIF).Methods:Microarray analysis was used to screen differentially expressed microRNAs and messenger RNA in SW480 cells. Real-time quantitative PCR (RT-qPCR) was used to detect the expressions of miR-451 and MIF in SW480 cells before and after transfection. Cell clone formation assay and Transwell assay were used to detect the proliferation and invasion of SW480 cells, respectively. Cell scratch assay was used to detect the migration ability of SW480 cells. The TargetScan database was used to analyze the correlation between miR-451 and MIF. Dual luciferase reporter gene was used to detect the interaction of miR-451 and MIF. MTT assay was used to detect the viability of SW480 cells.Results:Compared with human normal colorectal mucosal cell FHC (1.00), the expression of miR-451 was down-regulated in SW480 cells ( 0.36±0.18, P<0.001). Knockdown of miR-451 promoted proliferation, and migration of SW480 cells. Compared with that in FHC cells, MIF expression was up-regulated in SW480 cells (2.28±0.45, P<0.001). MIF down-regulation inhibited SW480 cell proliferation, invasion and migration. MiR-451 specifically bind to the MIF 3′UTR and regulated the expression of MIF. Overexpression of miR-451 reduced while overexpression of MIF increased the viability of SW480 cells. Overexpression of MIF promoted the proliferation and migration of SW480 cells ( P<0.01), reversed the effect of miR-451 suppressed proliferation and migration of SW480 cells. Conclusion:MiR-451 may regulate proliferation and migration of human colorectal cancer cells by targeting MIF.

Objective: To study the effects of a standardized diagnosis and treatment program for type 2 diabetes mellitus patients, in a community in Urumqi. Methods: In March 2016, 1 000 patients with type 2 diabetes at the Urumqi Xinhua Road community health service center and affiliated communities were selected to participate in a questionnaire survey and in a promotion for a 12-month standardized treatment. T-test and χ² test were used to compare the blood sugar, blood pressure, blood lipids, ratio of urine microalbumin and creatinine (urine A/C) and other metabolic indices in patients before and after the promotion. Results: In a total of 112 finalists, after a 4-month follow-up, rates of regular exercise, diet control, taking medication on time and regular blood glucose monitoring all improved significantly from 35.7%, 40.2%, 13.7%, 29.5% to 56.3%, 68.8%, 56.3%, 45.5%, respectively (χ²=9.508, 8.643, 45.319, 6.171; P < 0.05). The rates of smoking and drinking were lower after the promotion (χ²=4.291, 4.56; P < 0.05). Body mass index (BMI), fasting blood glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure, total cholesterol (TC), creatinine, and urine A/C decreased significantly, while there was no significant difference in the diastolic blood pressure. The percentage of participants with normal blood sugar, lipids and blood pressure, significantly improved from 38.4%, 37.5%, 23.6%, 8.9% to 63.4%, 66.4%, 43.7%, 23.2%, respectively. The rate of urine A/C positivity decreased from 40.2% to 26.8% (χ²=14.004, 18.309, 10.604, 8.473, 4.510, P < 0.05). Conclusion Standardized type 2 diabetes treatment programs can improve the blood levels of glucose and lipids, as well as lower blood pressure and the positive rate of urine A/C. It can help reduce the multiple risk factors and long-term complications by improving the self-management of diabetes.

Objective To analyze the effect of Noggin silencing on the BMP and Wnt signaling pathways in hair follicle development.Methods The expression of BMP-2, BMP-4, BMPR-IA, BMP-6, BMP-7, LEF-1 andβ-catenin in Noggin silencing MC3T3-E1 stable cell line was detected by RT-PCR and western blot.Results RT-PCR results showed that the expressions of five genes in BMP signaling pathway were all significantly influenced by Noggin silencing, the ex-pressions of BMP-2 (P<0.001), BMP-4 (P<0.01), BMP-6 (P<0.001) and BMP-7 (P<0.001) were all increased and the expression of BMPR-IA (P<0.01) was decreased.While the expressions of the two genes LEF-1 (P<0.001) and β-catenin ( P<0.001) in Wnt signaling pathway were significantly decreased.Western blot results showed that the ex-pressions of these proteins in the two signaling pathways were also affected.The expressions of BMP-2 (P<0.05), BMP-4 (P<0.05), BMP-6 (P<0.05) and BMP-7 (P<0.05) were all increased, while the expressions of BMPR-IA (P<0.05), LEF-1 (P<0.01) andβ-catenin (P<0.001) were decreased.Conclusions There may be a negative feedback regulation of Noggin on the BMP signaling pathway in vitro, but a positive feedback regulation on the Wnt signaling pathway in vitro.It provides certain evidence for studies on the effect of Noggin gene on BMP and Wnt signaling pathways in vivo. There may be an interaction between hair follicle development-related signaling pathways, which still needs further experi-ments to prove.

Objective To investigate the clinical effect of different surgical approaches on multi-level cervical spondylosis in elderly patients.Methods A total of 53 aged patients with multi-level cervical spondylosis (≥70 years old) who received operation in our department during May 2007 to May 2014 were retrospectively studied, and divided into anterior cervical surgical group (n=22) and posterior cervical group (n=31), according to the surgical approach.The operation duration, intraoperative blood loss, hospitalization time, postoperative complications, Japanese orthopedics association (JOA) scores, Neck disability index (NDI), postoperative subjective improvement of clinical symptoms and spinal fusion of the two groups were evaluated and compared respectively.Results The mean operative time was longer in the anterior surgical group than in the posterior surgical group [(2.7±0.5)h vs.(1.9±0.3) h, P＜0.05].The average blood loss of the anterior surgical group was less than that of posterior surgical group [(90.0±50.4) ml vs.(160.7±40.5)ml, P＜0.05].The hospitalization time of the anterior surgical group was less than that of posterior surgical group [(10.3±2.5) d vs.(15.7±3.6) d, P＜0.05].Postoperative JOA score of anterior surgical group was higher than that of posterior surgical group 6 months after surgery [(14.7 ±0.8)vs.(13.8±1.2), P＜0.05], while there was no significant difference in JOA score between the two groups up to the last follow-up [(14.8±1.2) vs.(14.7±1.8), P＞0.05].NDI score was lower in anterior surgical group than in posterior surgical group 3, 6, 12 months after operation and at the last follow-up.Among the 41 patients, radiographic outcomes showed that there were 16 cases of anterior surgical group with no bony fusion at the follow-up 3 months after operation, and all the 16 patients achieved bony fusion at the follow-up 1 year after operation, and there were 4 cases with titanium mesh subsidence (＜ 3 mm).Conclusions Both anterior cervical decompression and fusion and posterior cervical single open-door laminoplasty have good efficacy in the treatment of multilevel cervical spondylosis in elderly patients, which have advantages on the limb functional recovery time and cervical function assessment.When anterior cervical surgical contraindications were excluded, the anterior cervical decompression and fusion may be a good choice for the treatment of multilevel cervical spondylosis in aged patients.

BACKGROUNDBreast cancer has become one of the most common malignant tumors among females over the past several years. Breast carcinogenesis is a continuous process, which is featured by the normal epithelium progressing to premalignant lesions and then to invasive breast cancer (IBC). Targeting premalignant lesions is an effective strategy to prevent breast cancer. The establishment of animal models is critical to study the mechanisms of breast carcinogenesis, which will facilitate research on breast cancer prevention and drug behaviors. In this study, we established a feasible chemically-induced rat model of premalignant breast cancer.

METHODSFollowing the administration of the drugs (carcinogen, estrogen, and progestogen) to Sprague-Dawley (SD) rats, tumors or suspicious tumors were identified by palpation or ultrasound imaging, and were surgically excised for pathological evaluation. A series of four consecutive steps were carried out in order to determine the carcinogen: 7,12-dimethylbenzaanthracene (DMBA) or 1-methyl-1-nitrosourea, the route of carcinogen administration, the administration period of estrogen and progestogen, and the DMBA dosage.

RESULTSStable premalignant lesions can be induced in SD rats on administration of DMBA (15 mg/kg, administered three times) followed by administration of female hormones 5-day cycle.

RESULTSwere confirmed by ultrasound and palpation.

CONCLUSIONUnder the premise of drug dose and cycle, DMBA combined with estrogen and progestogen can be used as a SD rat model for breast premalignant lesions.

9,10-Dimethyl-1,2-benzanthracene ; Animals ; Breast Diseases ; chemically induced ; Disease Models, Animal ; Female ; Mammary Neoplasms, Experimental ; chemically induced ; Rats ; Rats, Sprague-Dawley

Parkinson's disease (PD) is a complicated disease, commonly diagnosed among the elderly, which leads to degeneration of the central nervous system. It presently lacks an effective therapy for its complex pathogenesis. Adverse effects from Western drug-based medical intervention prevent long-term adherence to these therapies in many patients. Traditional Chinese medicine (TCM) has long been used to improve the treatment of PD by alleviating the toxic and adverse effects of Western drug-based intervention. Therefore, the aim of this study is to evaluate the efficacy and safety of Xifeng Dingchan Pill (XFDCP), a compound traditional Chinese herbal medicine, taken in conjunction with Western medicine in the treatment of PD patients at different stages in the progression of the disease.