Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

ObjectiveTo investigate the association of menopausal time and menopausal age with the risk of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for the early prevention and treatment of NAFLD in clinical practice. MethodsRelated data were collected from 373 postmenopausal women who attended the outpatient service of Department of Spleen， Stomach， Liver and Gallbladder Diseases， The First Affiliated Hospital of Henan University of Chinese Medicine， from January 2017 to December 2021， including general information， menopausal age， menopausal time， and presence or absence of NAFLD. The chi-square test was used for comparison of categorical data； the independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups. A Logistic regression analysis was used to calculate the association intensity and 95% confidence interval （95%CI） of menopausal time and menopausal age for the risk of NAFLD， and the restricted cubic spline （RCS） method was used to investigate the dose-response relationship between menopausal time/age and the risk of NAFLD. ResultsCompared with the women with normal menopause or late menopause， the women with early menopause had a higher prevalence rate of NAFLD and a higher degree of steatosis and fibrosis （all P<0.05）. After adjustment for the confounding factors such as age and age of menarche， the risk of NAFLD in women with a menopausal time of >3 years was 4.80 （95%CI： 1.93‍ ‍—‍‍ ‍11.95， P=0.001） times that in women with a menopausal time of ≤3 years， and the risk of NAFLD in women with early or late menopause was 8.14 times （95%CI： ‍1.77 ‍— ‍37.58， P=0.007） and 0.09 times （95%CI： 0.03 ‍— ‍0.32， P<0.001）， respectively， that in those with a normal menopausal age. There is a dose-response relationship between menopausal time/age and the risk of NAFLD. Menopausal time is positively correlated with the association intensity of NAFLD， while menopausal age is negatively correlated with the association intensity of NAFLD. ConclusionThe longer the menopause time and the earlier the menopause age， the ligher the risk of NAFLD.

ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease （CMD）. MethodsPubMed， Cochrane Library， CNKI， Wanfang Data， and VIP were searched for the randomized controlled trials （RCTs） on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31， 2023. The primary outcome indicators included the index of microcirculatory resistance （IMR）， coronary flow reserve （CFR）， and corrected TIMI flow frame count （cTFC）. The secondary outcome indicators included symptomatic efficacy， left ventricular ejection fraction （LVEF）， hypersensitive C-reactive protein （hs-CRP）， nitric oxide （NO）， and adverse events. Cochrane risk-of-bias assessment tool 2.0 （RoB 2.0） and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations， Assessment， Development and Evaluation （GRADE） was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study， involving 3 029 patients. Compared with conventional Western medicine alone， the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR ［mean difference （MD）=-5.93， 95% confidence interval （95%CI） ［-8.73，-3.14］， n=382， P<0.01］， cTFC （MD=-9.35， 95%CI ［-13.94，-4.76］， n=618， P<0.01）， and hs-CRP ［standard mean difference （SMD）=-1.50， 95%CI ［-1.90，-1.11］， n=1 483， P<0.01］， improved the CFR （SMD=1.14， 95%CI ［0.08，2.19］， n=304， P=0.03）， symptomatic efficacy ［relative risk （RR）=1.36， 95%CI ［1.21，1.53］， n=756， P<0.01］， LVEF （MD=4.39， 95%CI ［2.31，6.47］， n=533， P<0.01）， and NO （SMD=3.16， 95%CI ［2.07，4.25］， n=946， P<0.01） of CMD patients. In terms of safety， the combined therapy reduced the occurrence of adverse events in CMD patients （RR=0.49， 95%CI ［0.29，0.82］， n=591， P=0.01）. GRADE showed moderate quality evidence for adverse events， low quality evidence for cTFC， symptomatic efficacy， LVEF， and NO， and very low quality evidence for IMR， CFR， and hs-CRP. ConclusionBased on microcirculatory function indicators， the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.

BACKGROUND:The Twin-block orthodontic appliance is commonly used for the correction of Class Ⅱ malocclusion.Its mechanism of action in stimulating mandibular growth has been confirmed in many studies,but its impact on maxillary growth is not very clear. OBJECTIVE:By establishing a finite element model to analyze the stress distribution of the maxillary complex,surrounding bone sutures,and maxillary dentition in patients with Class Ⅱ malocclusion wearing Twin-block orthodontic appliances. METHODS:One patient with Class Ⅱ malocclusion who underwent orthodontic treatment at Qingdao Hospital/Qingdao Municipal Hospital of Shandong Rehabilitation University was selected.The bite force data of the patient when wearing the Twin-block orthodontic appliance was measured,and CBCT data were collected.A finite element model was established,including the maxillary complex,peripheral sutures,Twin-block orthodontic appliance,and maxillary dentition.ABAQUS software was used to simulate the stress distribution in the maxilla and maxillary dentition when the patient was wearing the Twin-block appliance. RESULTS AND CONCLUSION:The equivalent stress on the maxillary anterior teeth was significantly smaller than that on the posterior teeth,and the maximum equivalent stress on both sides of the teeth were 4.797 5 Mpa and 8.716 1 Mpa,respectively,which were located at the first premolar.The maximum displacements were presented at the maxillary incisors on both sides of the teeth,which were 0.080 5 mm and 0.081 0 mm,respectively.The maximum equivalent stress on the bone suture was 1.284 Mpa,which was mainly concentrated in the pterygopalatine suture and the frontal-maxillary suture on both sides,and there was almost no difference in the force of the rest of bone sutures;the maximum displacement of the bone suture was 0.07 mm,with the pterygopalatine suture having the largest displacement,followed by the frontal-maxillary suture.The maximal equivalent stress on the maxillary complex was 27.18 Mpa,which was mainly concentrated on both sides of the anterior pyriform foramen of the maxilla,around the nasofrontal suture and around the pterygopalatine suture at the posterior part of the jaws.The maximal displacement of the maxilla was 0.07 mm,which was mainly concentrated on the maxillary alveolar bone.All these findings show that the occlusal force acts on the maxillary complex through the Twin-block appliance,resulting in clockwise rotation of the maxilla and steepening of the dentition plane.Measures should be taken to compensate for this tendency,for example,by considering maxillary molar elongation and intrusion in the process of occlusion,which are not only able to flatten the occlusal plane,but facilitate the mandibular protraction,thereby further improving Class Ⅱ malocclusion orthodontic treatment.

To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines； further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly； replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

ObjectiveTo investigate the spontaneous premature cardiac aging in SHJH^hr mice. MethodsA comparative study was conducted between SHJH^hr mice (SHJH^hr group) and wild-type ICR mice (WT group) at different ages (10 and 24 weeks). Cardiac function was analyzed using a small animal in vivo ultrasound imaging system. After euthanasia, organs were collected and weighed to assess the extent of cardiac atrophy. Cardiac pathological damage was observed using hematoxylin-eosin (HE) staining. Cardiac fibrosis was analyzed using Masson staining. Myocardial cell area was analyzed after wheat germ agglutinin (WGA) staining. The activities of oxidative damage indicators in myocardial tissue, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), as well as the content of 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured using enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of factors associated with inflammation, fibrosis, and oxidative stress. Colorimetric assay was used to measure malondialdehyde (MDA) levels. ResultsCompared to WT group mice of the same age, 10-week-old mice in the SHJH^hr group showed no significant differences in stroke volume (SV), ejection fraction (EF), fractional shortening (FS), or heart and lung weights. However, at 24 weeks of age, mice in the SHJH^hr group had significantly lower SV, EF, and FS values compared to mice of the same age in the WT group (P<0.05), with no significant change in lung weight but a significant reduction in heart weight (P<0.05). Histological analysis of heart tissue from 24-week-old mice revealed no significant difference in cardiac fibrosis levels between SHJH^hr and WT groups, but WGA staining showed a significant reduction in myocardial cell area in mice in the SHJH^hr group (P<0.05). PCR analysis revealed a significant downregulation of mRNA levels of oxidative stress factors Sod2, Gpx1, and Cat genes (P<0.05). Biochemical assays indicated significantly reduced activities of oxidative damage-related enzymes SOD, GPX, and CAT in myocardial tissue (P<0.05), while the levels of oxidative damage markers 8-OHdG and MDA significantly increased (P<0.05). ConclusionMice in the SHJH^hr group exhibit premature cardiac aging, which may be associated with oxidative stress damage in myocardial tissue.

ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion （I/R） injury in rats based on the changes of pericytes mediated by Ras homolog family member A （RHOA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK1） pathway. MethodsNinety rats （15 rats for each group） were randomly divided into a sham operation group， a model group， a positive control group receiving Ginkgo biloba extract （21.6 mg·kg^-1）， and groups receiving Naoxintong capsules at low， medium， and high doses of 55， 110， and 220 mg·kg^-1 （NXT-L， NXT-M， and NXT-H groups）， respectively. Except for those in the sham operation group， all rats were subjected to transient middle cerebral artery occlusion （tMCAO） to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager， and the cerebral infarction rate was calculated using 2，3，5-Triphenyl tetrazolium chloride （TTC） staining. Pathological changes were observed by hematoxylin-eosin （HE） staining and Nissl staining， while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of RHOA， ROCK1， platelet-derived growth factor receptor β （PDGFRB）， α-smooth muscle actin （α-SMA）， tight junction protein （ZO-1）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9）. ResultsCompared with the sham operation group， the model group exhibited decreased neurological function scores， higher percentage reduction in blood flow， and increased cerebral infarction rates （P<0.01）. Additionally， cortical neuronal nucleus shrinkage， edema， a decreased number of Nissl bodies， reduced pericyte area， elevated albumin content in the cortex （P<0.05）， and increased ischemic modified albumin levels （P<0.01） were observed. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were increased （P<0.01）， while those of ZO-1 were decreased. Compared with the model group， all treatment groups showed improved neurological function scores， lower percentage reduction in blood flow， reduced cerebral infarction rates （P<0.01）， alleviated cortical histological changes， increased number of Nissl bodies， expanded pericyte area， decreased albumin content in the cortex， and reduced ischemia-modified albumin levels （P<0.01）. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were decreased （P<0.01）， while those of ZO-1 were increased. Among the treatment groups， the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply， reduce microcirculation disturbance， and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.

ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion （I/R） injury in rats based on the changes of pericytes mediated by Ras homolog family member A （RHOA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK1） pathway. MethodsNinety rats （15 rats for each group） were randomly divided into a sham operation group， a model group， a positive control group receiving Ginkgo biloba extract （21.6 mg·kg^-1）， and groups receiving Naoxintong capsules at low， medium， and high doses of 55， 110， and 220 mg·kg^-1 （NXT-L， NXT-M， and NXT-H groups）， respectively. Except for those in the sham operation group， all rats were subjected to transient middle cerebral artery occlusion （tMCAO） to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager， and the cerebral infarction rate was calculated using 2，3，5-Triphenyl tetrazolium chloride （TTC） staining. Pathological changes were observed by hematoxylin-eosin （HE） staining and Nissl staining， while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of RHOA， ROCK1， platelet-derived growth factor receptor β （PDGFRB）， α-smooth muscle actin （α-SMA）， tight junction protein （ZO-1）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9）. ResultsCompared with the sham operation group， the model group exhibited decreased neurological function scores， higher percentage reduction in blood flow， and increased cerebral infarction rates （P<0.01）. Additionally， cortical neuronal nucleus shrinkage， edema， a decreased number of Nissl bodies， reduced pericyte area， elevated albumin content in the cortex （P<0.05）， and increased ischemic modified albumin levels （P<0.01） were observed. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were increased （P<0.01）， while those of ZO-1 were decreased. Compared with the model group， all treatment groups showed improved neurological function scores， lower percentage reduction in blood flow， reduced cerebral infarction rates （P<0.01）， alleviated cortical histological changes， increased number of Nissl bodies， expanded pericyte area， decreased albumin content in the cortex， and reduced ischemia-modified albumin levels （P<0.01）. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were decreased （P<0.01）， while those of ZO-1 were increased. Among the treatment groups， the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply， reduce microcirculation disturbance， and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.