Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

Objective To explore an overcorrection quantization method and related influencing factors through analyzing relationships between the achieved and preset intrusion values of mandibular anterior teeth with clear aligners.Methods Twenty pa-tients receiving Invisalign were recruited.The relative intrusion values in the ClinCheck software were recorded as the preset intrusion.The achieved intrusion values were measured through the digital model superimposition.Statistical analysis was conducted to assess the differences and linear relationships between the preset and achieved intrusion values,and investigate the effect of related factors such as intrusion amounts on the intrusion efficiency.Results For the mandibular anterior teeth,the mean intrusion efficiency was 62.2%,with the highest in the central incisors and the lowest in the canines.The intrusion amounts,incisors labial inclinations,and canine at-tachment types affected the intrusion efficiency.The differences between the preset and achieved values were significant,and the linear relationship existed.The formula of the intrusion overcorrection for the mandibular anterior teeth is"Z=(W-0.110)/0.533-W".Z re-presents the overcorrection and W represents the ideal intrusion.Conclusion The preset intrusion values in the treatment protocol could not be fully achieved.Moreover,correction should be designed in cases of mandibular canine intrusion,large amountsof intru-sion,orlingually inclined incisors.Compared to the optimized attachments,the vertical rectangular attachments on the mandibular ca-nines could improve the efficiency.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

Objective To explore the chemical basis of Shenxianshengmai oral liquid.Method UHPLC-Q Exactive Focus MS/MS technology was used to identify the chemical components of Shenxianshengmai oral liquid.The chromatographic separation was performed on a Thermo Accucore aQ C18 column(150 mm×2.1 mm,2.6 μm)with mobile phase gradient elution of 0.1%formic acid aqueous solution(A)and methanol(B)for 0-13 min,5%-60%B;13-27 min,60%-95%B;27-30 min,95%B,the flow rate was 0.3 mL·min-1,and the column temperature was at 30℃.The mass spectrometry was performed by heating electrospray ionization(H-ESI)with positive and negative ion scanning modes.The scanning range was m/z 120-1800,and the collision energies were 30 eV,50 eV and 70 eV.Result A total of 160 components were identified,including 29 flavonoids,24 organic acids,21 alkaloids,19 terpenoids,15 phenylpropanoids,12 saponins and 40 other components.Six chemical constituents(rutin,psoralenoside,isopsoralenoside,psoralen,isopsoralen and bakuchiol)were confirmed by comparison with reference substances.Conclusion In this study,an UHPLC-Q Exactive Focus MS/MS method has been established for accurate,rapid and systematic identification of the constituents in Shenxian Shengmai oral liquid,which provides an important basis for clarifying the chemical basis and quality control.

BACKGROUND:The reciprocal force generated by the molar distalization with clear aligners can lead to anchorage loss.The effect of arch shapes and missing second premolars on anchorage has not been reported. OBJECTIVE:To analyze the effect of arch shapes and missing second premolars on anchorage during molar distalization with clear aligners using the finite element method. METHODS:Cone-beam CT data from an adult male were acquired from the database to establish the maxilla-upper dentition-periodontium-rectangular attachment-clear aligner model.The distal movement amount designed on the bilateral second molars was set to 0.25 mm.First,there were two groups in the study:second premolar bilateral presence and absence groups.Then,four subgroups in each group were created:tapered arch,ovoid arch,square Class Ⅱ Division 1 arch,and Class Ⅱ Division 2 arch groups.The Ansys software was used to calculate the displacement of the anchorage tooth and the stress of the periodontal ligament. RESULTS AND CONCLUSION:Mesial tipping and extrusion of first molars and premolars,labial inclination and intrusion of anterior teeth occurred during the upper second molar distalization with clear aligners.When the bilateral second premolars were missing,the mesial displacement of first molars increased significantly while that of first premolars and anterior teeth decreased in all groups.The square Class Ⅱ Division 1 arch group showed the least anterior labial inclination,while the tapered arch group showed the most.There was no significant difference between the ovoid arch group and the tapered arch group.Moreover,the magnitude of tipping in the square Class Ⅱ Division 2 arch group was slightly higher than that in the Class Ⅱ Division 1 arch group.The stress of the periodontal ligament of the anchorage teeth was concentrated on the cervical and apical regions of the teeth.And the lowest stress level was detected in the square arch group.Compared with the other groups,the stress on the labial cervical area of the periodontal ligaments was also significantly relieved in the square arch group.To conclude,the square arch is more favorable in terms of anterior anchorage control and periodontal ligament stress distribution.Anterior labial inclination efficiency can be increased in cases of Class Ⅱ Division 2 by designing the anterior labial inclination in conjunction with molar distalization.If the second premolar is missing during molar distalization,it is not conducive to opening up the space in the area of the missing tooth.

BACKGROUND:The thin alveolar bone in the lower anterior region increases the risk of labial bone resorption when intruding the teeth with clear aligners.The effect of sagittal overcorrection design on the labiolingual control of mandibular anterior teeth intrusion has not been fully investigated. OBJECTIVE:To explore the effect of overcorrection on the changes in the displacement and stress of the mandibular anterior teeth,especially the cervical and apical regions. METHODS:Through a male volunteer cone-beam CT data,the three-dimensional reconstruction of the mandible and teeth was conducted in the MIMICS and GEOMAGIC software.Moreover,the models of periodontal ligaments,attachments,and appliances were created in the SOLIDWORKS software.First,the study was divided into canine intrusion group and incisor intrusion group.Then,the overcorrection(0°,1°,2°)was designed on the bilateral mandibular central and lateral incisors.A total of six models were established.The models were assembled and imported into the ANSYS software to analyze and calculate the displacement and stress level. RESULTS AND CONCLUSION:(1)In the canine intrusion group,canines intruded and tipped lingually while incisors extruded and tipped lingually.In the incisor intrusion group,canines extruded and tipped lingually while incisors intruded and tipped lingually.(2)Without overcorrection,the incisors necks moved lingually while apexes moved labially.With overcorrection,the incisors tended to be upright,followed by labial tilt.The least cervical and apical displacements were detected under 1° overcorrection.(3)With overcorrection,the incisal cervical stress concentration area shifted from labial to lingual in the canine intrusion group,whereas the stress concentration area shifted from lingual to labial in the incisor intrusion group.(4)The incisors tended to tilt lingually when intruding the mandibular anterior teeth with clear aligners.The sagittal overcorrection design was conductive to maintain the stable position of incisors.However,the amount of overcorrection should be moderate.Excessive overcorrection might increase the labial inclination tendencies of incisors.

AIM:To investigate the mechanism of action of Wenweiyang decoction(WWYD)in treating func-tional dyspepsia in rats based on mast cell activation and stem cell factor(SCF)/receptor tyrosine kinase c-Kit signaling pathway.METHODS:Sixty SD rats were randomly divided into control group,model group,ranitidine hydrochloride capsule group,and low-,medium-and high-dose WWYD groups,with 10 rats in each group.The rat model of functional dyspepsia was established by tail clamping and irregular feeding compound senna method.After modeling,the rats in con-trol group and model group were given normal saline,while those in low-,medium-and high-dose(0.743 g/mL,1.485 g/mL and 2.970 g/mL)WWYD groups and ranitidine hydrochloride capsule(3 g/L)group were treated with corresponding drugs by intragastric administration.After treatment,the propulsion rate of the small intestine was measured by the carbon ink propulsion method.Rat duodenal mast cells were observed and counted by toluidine blue staining.ELISA was used for determination of mast cell tryptase(MCT)and histamine(HA)content in rat duodenum.The mRNA levels of SCF and c-Kit in duodenum were detected by RT-qPCR.Western blot and immunohistochemistry were employed to determine the ex-pression levels of SCF and c-Kit in the duodenum.RESULTS:Compared with model group,WWYD treatment signifi-cantly increased the propulsion rate of the small intestine in rats(P<0.05).ELISA results showed that WWYD reduced the number of mast cells and the content of MCT and HA in the duodenal mucosa tissue of rats(P<0.05).Western blot and immunohistochemistry results suggested that WWYD up-regulated the protein expression levels of c-Kit and SCF in the duodenal tissue of rats(P<0.05),and increased the numbers of SCF and c-Kit positive cells.RT-qPCR results indicated that WWYD up-regulated the mRNA expression of c-Kit and SCF in the duodenum of rats(P<0.05).Moreover,the small intestinal propulsion rate was negatively correlated with MCT and HA content,and positively correlated with the expres-sion of SCF and c-Kit.CONCLUSION:Wenweiyang decoction promotes rat duodenal motility,and its mechanism may be related to the inhibition of rat duodenal MCT and HA production and activation of SCF/c-Kit signaling pathway.

Fengweiqi is the whole plant of Rhodiola dumulosa.It is a kind of natural and precious folk medicinal plant,mainly distributed on hillside rocks and crevasses at the altitude of 1 600-4 100 m.Fengweiqi mainly contains flavonoids,volatile oil,polysaccharides,various amino acids and trace elements.Modern pharmacological studies have shown that Fengweiqi has many significant pharmacological activities,such as anti-oxidation,anti-fatigue,anti-hypoxia and bacteriostasis.In this paper,the textual research,chemical constituents,pharmacological actions and artificial cultivation of Fengweiqi were reviewed in order to provide reference for further research and development of Fengweiqi resources.

As a common clinical Chinese medicine, Prunellae Spica has the effects of clearing liver-fire, improving eyesight, resolving massesand detumescence, and has strong anti-tumor effects against thyroid cancer, breast cancer, liver cancer and other cancers. Extracts of Prunellae Spica and its active components can play an anti-tumor role in a variety of ways, including cell apoptosis, inhibiting cell invasion and metastasis, inhibiting cell proliferation, inducing autophagy, anti tumor angiogenesis, reversing tumor multidrug resistance and regulating immune function, by regulating miRNA and Wnt/β-catenin, PI3/AKT, AMPK/mTOR/ULK1, RANKL/RANK/OPG and other signal pathways . In this paper, the anti-tumor mechanism of Prunellae Spica extract was reviewed, in order to provide reference for further research and application.