Efficacy and safety of acupuncture for postpartum hypogalactia: protocol for a systematic review and meta-analysis.

INTRODUCTION: Breast milk is recognised as the best natural food for neonates, but many women experience postpartum hypogalactia (PH). Randomised trials have found that acupuncture exert therapeutic effect on women with PH. However, systematic reviews on the efficacy and safety of acupuncture are still lacking; therefore, this systematic review aims to evaluate the efficacy and safety of acupuncture for PH. METHODS AND ANALYSIS: Six English databases (PubMed, Cochrane Library, EMBASE, EBSCO, Scopus, and Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Wan-Fang, Chinese Biomedical Literature and Chinese Scientific Journal) will be systematically searched from their establishment to 1 September 2022. Randomised controlled trials of the efficacy of acupuncture for PH will be reviewed. The study selection, data extraction and research quality evaluation will be conducted independently by two reviewers. The primary outcome is the change in serum prolactin level from baseline to the end of treatment. Secondary results include milk secretion volume, total effectiveness rate, degree of mammary fullness, rate of exclusive breast feeding, and adverse events. A meta-analysis will be performed using RevMan V.5.4 statistical software. Otherwise, a descriptive analysis will be conducted. The risk of bias will be assessed using the revised Cochrane risk-of-bias tool. ETHICS AND DISSEMINATION: This systematic review protocol does not require ethical approval because it does not include private information/data of the participants. This article will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42022351849.

16S rDNA analysis of osteoporotic rats treated with osteoking.

Introduction. Osteoporosis (OP) is characterized by microstructural degeneration of bone tissue, low bone mass, bone fragility and even brittle fracture (osteoporotic fracture, OPF). OP and OPF are common and there are many disadvantages to the current medications for OP/OPF. Osteoking is a traditional Chinese medicine (TCM) originating from the Yi nationality (Yunnan, China) that has been used to treat bone diseases for decades.Hypothesis/Gap Statement. This study will reveal the changes in the intestinal microbiota of OP rats after 70 days of osteoking treatment.Method. With duplication of sham and OP rats, eight groups were established, with six rats in each group. The intestinal microbiotas were analysed by 16S rDNA sequencing.Results. The results showed that osteoking changed the intestinal microbiota of sham rats and OP rats. The mechanism by which osteoking improves OP is related to the functions of the intestinal microbiota. After 70 days of treatment with osteoking, the contents of Pseudonocardia, Pedomicrobium, Variovorax, Niastella and Actinosynnema were decreased in OP rats. The functions of the above intestinal microbiota related to iron metabolism affected calcifediol and 25(OH)D, and measuring these bone metabolic indicators is required for further study.Conclusion. Osteoking changes the intestinal microbiota to improve OP, and further study which reveals these intestinal microbiota and mechanism is needed.

Symptoms Based on Deficiency Syndrome in Traditional Chinese Medicine Might Be Predictor of Frailty in Elderly Community Dwellers.

BACKGROUND: The most widely used frailty phenotype and frailty indexes are either time-consuming or complicated, thus restricting their generalization in clinical practice; and therefore, an easier and faster screening tool is needed to be developed. OBJECTIVE: To select sensitive symptoms in traditional Chinese medicine (TCM) and study whether they can improve the risk prediction of frailty. METHODS: This is a cross-sectional study enrolling 2249 Chinese elderly community dwellers. Data were collected via face-to-face inquiries, anthropometric measurements, laboratory tests, and community health files. Frailty was the main outcome measure, and it was evaluated by Fried's frailty phenotype (FP). The ordinal logistic regression model was used to identify the factors associated with frailty. The risk assessment plot was used to compare the discriminative ability for frailty among models with and without TCM symptoms. RESULTS: The identified sensitive influential factors for frailty included age, education level, dietary habits, chronic obstructive pulmonary disease, diabetes, cerebral infarction, osteoporosis, cold limbs, lethargy and laziness in speaking and moving, weakness of lower limbs, slow movement, dry mouth and throat, and glazed expression. The risk prediction for "frailty cumulative components ≥1" was not significantly increased, while for "frailty cumulative components ≥2", a new model developed with the above selected TCM symptoms had a higher AUC than the baseline model without it (0.79 VS 0.81, P=0.002). And the NRI and IDI for the new model were 41.4% (P=0.016) and 0.024% (P=0.041), respectively. CONCLUSION: This research might provide an easier and faster way for early identification and risk prediction of frailty in elderly community dwellers.

Osteoking improves OP rat by enhancing HSP90­ß expression.

Osteoporosis (OP) is a chronic bone disease that affects individuals worldwide. Osteoporosis is primarily asymptomatic, and patients with OP suffer from pain, inconvenience, economic pressure and osteoporotic fracture (OPF). Osteoking, a Traditional Chinese Medicine compound that originates from the Yi ethnic group, has been used for a number of years to treat fractures. In our previous study, osteoking exhibited therapeutic effects on rats with OPF by promoting calcium deposition. Based on bioinformatics and network pharmacology analyses of a component­target­disease database, heat shock protein HSP 90­ß (HSP90­ß), also known as HSP90­ß, was identified to be a key target of osteoking in OP. High HSP90­ß expression levels were observed in osteoporotic rats and rat bone mesenchymal stem cells (rBMSCs) following osteoking treatment. After 12 weeks of administration in vivo, there was increased bone mineral density (BMD) (P<0.05), increased bone alkaline phosphatase (P<0.05), and improved bone microstructure in the osteoking group compared with those of the negative control group. In vitro, increased calcium deposition in rBMSCs was observed after 4 weeks of osteoking treatment. These results suggest that the mechanisms of osteoking are closely associated with HSP90­ß and activate the bone morphogenetic protein (BMP) signalling pathway, primarily through BMP­2. Osteoking treatment improves OP in rats by enhancing HSP90­ß expression.

[Effect of Osteoking on Bone Mineral Density and Dickkopf-1 Protein Levels in Rabbits with Osteoporotic Fracture].

OBJECTIVE: To explore the effect of Osteoking on bone mineral density (BMD) and serum Dickkopf-1 (DKK-1) protein levels in rabbits with osteoporotic fracture (OPF). METHODS: Totally 45 female Japanese big-ear rabbits were randomly divided into the treatment group, the model group, and the blank control group (as the control group), 15 in each group. Bilateral ovaries were ectomized for 24 weeks in the treatment group and the model group. Their left radial factures were induced after confirmed osteoporosis. Rabbits in the treatment group were administered with Osteoking by gastrogavage, once per two days. Equal volume of normal saline was given to rabbits in the model group. The general BMD and serum DKK-1 protein levels were detected before ovariectomy, at week 24 and 48 after ovariectomy. RESULTS: There was significant difference in the general BMD at week 24 after ovariectomy between the model group and the control group, and it was lower in the model group. Compared with the model group, the general BMD significantly increased and serum DKK-1 protein levels significantly decreased in the treatment group after intervention. Serum DKK-1 protein levels were significantly lower after intervention than before intervention in the treatment group. CONCLUSION: Osteoking could improve the BMD of OPF rabbits, and reduce their serum DKK-1 protein levels as well.

[Wnt/ß-catenin signal pathway mediated Salidroside induced directional differentiation from mouse mesenchymal stem cells to nerve cells].

OBJECTIVE: To explore the molecule mechanism of Salidroside inducing directional differentiation of mouse mesenchymal stem cells (MSCs) into neuronal cells. METHODS: The mouse multipotent mesenchymal precursor cell line (D1) was taken as the objective. Cultured MSCs were divided into the negative control group (complete culture solution), the positive control group (containing 1 mmol/L ß-mercaptoethanol), the Salidroside induced group (20 mg/L Salidroside), and the blocked group (20 ng/ ml DKK1, a special inhibitor of Wnt/ß-catenin signal pathway). All cells were inoculated in a 6-well plate (1 x 10(4) cells/cm2) and grouped for 24 h. The expression of p-catenin was detected by fluorescence Immunochemistry in the negative control group, the positive control group, and the Salidroside induced group. The expression of neuron-specific enolase (NSE), beta 3 class III tubulin (ß-tubulin III), nuclear receptor related factor 1 (Nurr1), glial fibrillary acidic protein (GFAP) mRNA, Wnt3a, ß-catenin, low-density lipoprotein receptor-related protein6 (LRP6), Axin mRNA were detected using reverse transcrip- tion PCR (RT-PCR). The expression of ß-catenin and NSE protein were analyzed by Western blot in the negative control group, the positive control group, and the Salidroside induced group. Ca2+ chelating agents (EGTA), L-type Ca2+ channel blocker (Nifedpine), and IP3Ks special inhibitor (LY294002) were used to block Ca2+ signal pathway respectively. The expression of Wnt3a, LRP-6, Axin, glycogen syn- thase kinase (GSK-3), and ß-catenin mRNA were detected by RT-PCR. The ß-catenin protein expression was analyzed using Western blot. RESULTS: Compared with the positive control group, ß-catenin protein was strong positively expressed; the expression of Wnt3a, ß-catenin, LRP6, Axin, NSE, ß-tubulin III, Nurr1 mRNA, and NSE protein were obviously up-regulated in the Salidroside induced group (P < 0.01). Compared with the positive control group and the Salidroside induced group, ß-catenin, NSE, Nurr1, and ß-tubulin III mRNA expression decreased; ß-catenin and NSE protein expression were also down-regulated in the blocked group (P < 0.01). Compared with the Salidroside induced group, the expression of Wnt3a, LRP-6, ß-catenin, and Axin mRNA were down-regulated in the Ca2+ signal blocked group and the salidroside induced group (P < 0.01, P < 0.05). CONCLUSION: Salidroside affected directional differentia- tion of MSCs into neuronal cells through Wnt/ß-catenin and Ca2+ signal pathway.

Salidroside induces neuronal differentiation of mouse mesenchymal stem cells through Notch and BMP signaling pathways.

Salidroside (p-hydroxyphenethyl-ß-D-glucoside, SAL), a phenylpropanoid glycoside isolated from a popular traditional Chinese medicinal plant Rhodiola rosea L., possesses multiple pharmacological actions. Previous study showed that SAL could induce rat mesenchymal stem cells (MSCs) to differentiate into dopaminergic neurons and induce mouse MSCs D1 to differentiate into neuronal cells. However, the mechanisms of SAL-induced neuronal differentiation of MSCs still need investigation. In this study, we observed the effects of SAL on neuronal differentiation of D1 cells and the possible involvement of Notch and BMP signaling pathways. SAL inhibited the proliferation, induced neuronal phenotypes, and upregulated the expressions of neuronal-specific marker molecules, such as neuronal enolase 2 (Eno2/NSE), microtubule-associated protein 2 (MAP2), and beta 3 class III tubulin (Tubb3/ß-tubulin III) in D1 cells. SAL not only downregulated the expressions of Notch1 and hairy enhancer of split 1 (Drosophila) (Hes1) but also upregulated the expression of Smad1/5/8 and its phosphorylation (p-Smad 1/5/8). The neuronal differentiation effects of SAL on D1 cells were promoted by a Notch signaling antagonist, DAPT, but attenuated by a BMP signaling pathway antagonist, Noggin. Our findings suggest that SAL might be promising in inducing neuronal differentiation of mouse MSCs mediated by both Notch signaling pathway and BMP signaling pathway.

[Salidroside via ERK1/2 and PI3K/AKT/mTOR signal pathway induces mouse bone marrow mesenchymal stem cells differentiation into neural cells].

To investigate the role of the extracellular signal-regulated kinase (ERK1/2) and PI3K/AKT/ mTOR signal pathway inducing bone marrow mesenchymal stem cells (BMSCs) differentiation into neural cells, mouse bone marrow-derived mesenchymal stem cell lines D1 cells were used as research object. And they were divided into control groups and salidroside (SD) groups. Different concentrations (5, 25, 50, 100 and 200 microg x mL(-1) of SD were used and SD (100 microg x mL(-1)) was used to induce at different time (0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h). The immunofluorescence staining chemical technology, real-time PCR and Western blotting were used to detect the positive rates of NSE, MAP2, beta-Tubulin III, NES, GFAP and the expression levels of beta-Tubulin III, NSE, ERK1/2, AKT. The expression of ERK1/2 and NSE was detected when the ERK1/2 and PI3K/AKT/ mTOR signal pathway was blocked by PD98059 and LY294002. It indicated that the positive rates of NSE, MAP2, beta-Tubulin III, NES and GFAP were gradually enhanced with time increased. The expression level of NSE and beta-Tubulin III protein were significantly higher than those in control groups (P < 0.01). The expression of ERK1/2, AKT mRNA and protein were higher with concentration and time increased. When the ERK1/2 and PI3K/AKT/mTOR signal pathway were blocked, the expression levels of NSE, NES and beta-Tubulin III mRNA and NSE protein were inhibited significantly. It points out that SD can stimulate the ERK1/2 and PI3K/AKT/mTOR signal pathway to promote BMSCs differentiation into neural cells.

[Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: a randomized controlled trial].

BACKGROUND: Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by its gradual progression. At present, the cause and mechanism of AD are yet unclear, and there is no effective therapy for treating it. With development of global aging, the prevalence rate of AD is increasing. The life quality of elderly people is affected severely by AD that is ultimately life-threatening. Recently, study on treating AD with traditional Chinese medicine (TCM) has deepened. OBJECTIVE: To explore the therapeutic effects of a syndrome differentiation-based TCM regime in treating patients with mild to moderate AD for improving cognition, and to evaluate the changes in brain function of AD patients observed by resting-state functional magnetic resonance imaging (fMRI) technique. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Adopting the internationally recognized criteria developed by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association, the clinical trial was conducted on 131 patients with mild to moderate AD from 5 communities and 7 social welfare institutions. Participants were accepted after informed consent was received, and laboratory tests and a head imaging study were conducted. The patients were randomly divided into Chinese medicine group (CMG) (66 cases) or Western medicine group (WMG) (65 cases). Patients in the CMG were treated monthly with Chinese medicine according to syndrome differentiation. Patients in the WMG were treated with donepezil at a dose of 5 mg once daily. The therapeutic course lasted 48 weeks. MAIN OUTCOME MEASURES: The scores of Mini-Mental State Examination (MMSE), Fuld Object-Memory Evaluation (FOM), Block Design (BD) and Digit Span (DS) were used to evaluate the cognitive function; resting-state fMRI was used for observing brain function. The questionnaires and fMRI were performed before and after treatments. RESULTS: The cognitive functions of the patients in the CMG and WMG were improved after treatment. MMSE score was improved significantly in both groups (P<0.05 or P<0.001). After 48 weeks of treatment, 70.91% patients in the CMG had an improved MMSE score and 20% got worse, however, 55.77% patients in the WMG were improved in MMSE score and 34.62% got worse. Scores of FOM denominator and BD increased significantly in both groups; scores of FOM numerator and DS were also increased in the CMG (P<0.05 or P<0.01). The results of fMRI suggested that both Chinese medicine and donepezil treatment improved the connectivity between posterior cingulated gyrus and specific areas in the brain. The influence range of Chinese medicine primarily impacted on the left parietal lobe, being less than the influence range of donepezil, which primarily affected both sides of frontal lobes. CONCLUSION: TCM treatment based on syndrome differentiation is effective in improving cognitive function of patients with mild to moderate AD and increasing the brain function by increasing connectivity between posterior cingulated gyrus and specific areas in the brain.

[Experimental study on osteoking in promoting gene expression of core binding factor alpha 1 in necrotic femoral head of rabbits].

OBJECTIVE: To study the effects of Osteoking in promoting gene expression of core binding factor alpha 1 (cbfalpha 1) in necrotic femoral head of rabbits. METHODS: Rabbit model of femoral head necrosis (FHN) was induced by intravenous injection of lipopolysaccharide (LPS) 10 microg/kg body weight twice with an interval of 24 h and intramuscular injection with methyl prednisone (MPS) 20 mg/kg body weight 3 times. The dynamic changes of cbfalpha 1 gene expression in the femoral head were observed with immunohistochemistry and real-time quantitative PCR. RESULTS: The protein expression of cbfa 1 gene was negative in both model and treatment groups at the 4th week, it turned to weakly positive in the treatment group at the 8th and 12th week but still negative in the model group. The mRNA expression of cbfalpha 1 in the treatment group was 2.87 times that in the model group at the 12th week. There was no significant difference in cbfalpha 1 expression between the normal rabbits with or without Osteoking treatment. CONCLUSION: Osteoking could promote the endogenous cbfalpha 1 expression in the FHN, the effect is better along with the prolonging of the time applied. But it showed no affection on cbfalpha 1 expression in the normal femoral head of rabbits.

Clinical study on effect of Osteoking in preventing postoperational deep venous thrombosis in patients with intertrochanteric fracture.

OBJECTIVE: To evaluate the effect of Osteoking ( masculine(1)i) in preventing postoperational deep venous thrombosis (DVT) in patients with intertrochanteric fracture (ITF). METHODS: With prospective and randomized controlled clinical design adopted, 62 patients with ITF after operation were assigned into 2 groups, the tested group and the control group, Osteoking (25 ml every other day) and Sanchi-dansheng tablets (3 tablets thrice a day) were given orally to them respectively for 10 days. Difference of round length of thighs and shanks between two sides were measured on the 10th day and Doppler ultrasonic examination on the fractured leg was carried out. RESULTS: The occurrence rate of DVT in the tested group was 9.4%, which was lower than that in the control group (30.0%, P < 0.05). All the difference of round lengths, either that of the thigh or the shank, was less in the tested group than that in the control group, showing statistical significance (P < 0.05). CONCLUSION: Osteoking has a satisfactory effect in preventing postoperational DVT in patients with ITF.