ObjectiveTo explore the effects of the Tai Chi training on bone density， bone turnover markers， and heart rate variability for people with high-risk osteoporosis， and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included， and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week， and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group， and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L₁~L₄ vertebrae， bilateral femoral necks and bilateral total hips in the two groups before and after the intervention； enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention， including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide （P1NP） and β-collagen type Ⅰ cross-linking carboxy-terminal peptide （β-CTX）. Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor， they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each， and the heart rate variability （HRV） during exercise was collected， including time-domain indexes such as standard deviation of normal sinus intervals （SDNN）， root-mean-square of the difference between adjacent RR intervals （RMSSD）， frequency-domain metrics such as low-frequency power （LF）， high-frequency power （HF）， and low-frequency/high-frequency power ratio （LF/HF）， as well as nonlinear metrics such as approximate entropy （ApEn）， sample entropy （SampEn）. ResultsFinally， 63 cases were included in the outcome analysis， including 30 cases in the intervention group and 33 cases in the control group. After the intervention， the differences of L₁~L₄ vertebrae， bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention （P＞0.05）， while the bone density of all parts of the control group decreased significantly compared with that before intervention （P＜0.05）， and the difference in the bone density of the L₁~L₄ vertebrae， bilateral femoral neck， and the right total hip before and after the intervention of the intervention group was smaller than that of the control group （P＜0.05）. The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant （P＞0.05）. Compared with walking exercise， LF decreased， HF increased and LF/HF decreased during Tai Chi exercise （P＜0.05）； the time domain indexes and non-linear indexes between groups had no statistically significant difference （P＞0.05）. ConclusionTai Chi exercise can maintain lumbar， hip， and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis， but cannot significantly improve bone turnover markers.

ObjectiveTo observe the clinical characteristics and influencing factors of adverse events of Osteoking and provide a basis for its rational use in clinical practice. MethodA prospective and multicenter Cohort study with large samples was conducted to observe the effects of Osteoking in the treatment of 922 patients with knee osteoarthritis from 20 hospitals from May 1， 2020 to December 31， 2021. Patients who were treated with Osteoking were set as the exposed cohort， and those who were not treated with Osteoking were set as the non-exposed cohort. The gender， age， body mass index （BMI）， occupation， allergy history， past medical history， hospital information， medication， and the occurrence of adverse events of the patients were recorded， and the incidence of adverse events was analyzed， as well as its characteristics and factors. ResultA total of 922 patients with knee osteoarthritis were involved， including 274 males （29.72%） and 648 females （70.28%）， from which 617 cases were in the exposed cohort， and 305 cases were in the non-exposed cohort. A total of 25 adverse events occurred in both cases， accounting for 2.71% of the total number of cases， with 17 cases in the exposed cohort （2.76%） and eight cases in the non-exposed cohort （2.62%）. There was no difference in the incidence rate between the two groups （P=0.907）. The age group with the highest incidence of adverse events was between 50 and 59 years old in the exposed cohort （4.61%）. The incidence rate in women was 3.49%， slightly higher than 1.07% in men， but there was no difference （P=0.156）. According to the systematic classification of adverse events， five cases were respiratory， thoracic， and mediastinal diseases， with an incidence rate of 0.81%. There were two cases of infection and infection diseases， two cases of skin and subcutaneous tissue diseases， two cases of heart-related diseases， two cases of symptoms and signs （not otherwise classified）， and two cases of eye organ diseases， and the incidence rate was 0.32%. There was one case of systemic disease， one case of neuropathy， one case of heart organ disease， and one case of vascular hypotension disease， and the incidence rate was 0.16%. During the trial， a total of seven adverse reactions occurred. Among them， there were two cases of dry pharynx， two cases of dizziness， one case of drowsiness， one case of hypotension， and one case of eye discharge， with an incidence rate of 1.13%. Through binary Logistic regression analysis， it was found that among the factors that may affect the occurrence of adverse events in the exposed group， traditional Chinese medicine hospitals were the protective factors for the occurrence of adverse events （OR=0.200， P=0.002）， while gender， age， BMI， occupation， allergy history， past medical history， and hospital level cannot be considered to have an impact on the occurrence of adverse events. ConclusionOsteoking can be used to treat knee osteoarthritis of patients of all ages and genders by doctors from hospitals of different levels with higher safety， with occasional and mild adverse events， and seeing a doctor in a traditional Chinese medicine hospital can reduce the occurrence of adverse reactions.

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

ObjectiveTo investigate the improvement of the efficacy of Osteoking in patients with knee osteoarthritis in the onset and remission stage and to systematically explore its potential intervention mechanism， so as to provide a certain reference for improving the clinical application value of Osteoking and guiding its clinical rational drug use. MethodThrough the real-world study of the treatment of knee osteoarthritis with Osteoking， the data was obtained and entered into the "Osteoking for the treatment of knee osteoarthritis case registration system"， and 105 patients with episodic and remission knee osteoarthritis from the outpatient or inpatient orthopedic department of 20 medical institutions， including the Third Affiliated Hospital of Beijing University of Chinese Medicine， Peking Union Medical College Hospital， Wangjing Hospital of the Chinese Academy of Chinese Medical Sciences and Hunan Aerospace Hospital， from May 1， 2020 to December 31， 2021， were selected in the system. It included 60 patients treated with Osteoking and joint injection， and 45 patients treated with joint injection alone. The WOMAC osteoarthritis index score， visual analogue （VAS） pain score， individual types of pain symptoms （cold pain， hot pain， tingling， dull pain， soreness） and other TCM symptoms were observed and compared between the two groups， and statistically analyzed. In order to further elucidate the potential molecular mechanism of Osteoking combined with joint injection in the treatment of knee osteoarthritis in the treatment of onset and remission， this study used the "Bone Injury Cross Database （http：//bone-xtrans.com/database，BX-Data）" to collect the gene set of knee osteoarthritis disease， the traditional Chinese medicinal materials， chemical composition， material base， candidate target， candidate target， sodium hyaluronate candidate target data for screening， and constructed an interaction network of "disease target". ResultsAmong the 105 patients with knee osteoarthritis enrolled， 15.24% （16/105） were in the episodic period， 84.76% （89/105） were in remission， and there were no convalescent patients. There were 72 cases （68.57%） in women， 33 cases （31.43%） more than men， 60 cases in the observation group and 45 cases in the control group in 105 patients. There were 20 patients with a VAS score of 5 and 19 patients with a score of 6 in the observation group， accounting for 65.00% of the observation group. The comparative results of VAS scores between groups before and after treatment showed that the scores of the two groups were （4.42±1.01） scores， （5.00±1.02） scores.4 weeks after treatment， and （3.12±1.04） scores and （3.56±1.08） scores，8 weeks after treatment， respectively， which were lower than those before treatment （6.23±1.28） scores，（ 6.02±1.22） scores （P<0.05）， and the comparative results of the pain properties of the two groups showed that the improvement rates before and after thermal pain and tingling in the observation group were 3.3%（2/60） and 16.7%（10/60）， respectively. The control group was 2.2% （1/45）and 15.6%（7/45）［（χ²=4.034、13.583，P<0.05）］， respectively， and the improvement rate of cold pain and soreness in the observation group was 5.0%（3/60） and 3.3%（2/60）， which was higher than that of the control group . The results of comparing the WOMAC scores before and after treatment of the two groups showed that the difference between the stiffness score before and after treatment in the observation group was （1.68±1.42） scores， the difference between the score before and after treatment in the control group was （1.20±1.60） scores （P<0.05）， and the pain score before and after treatment was （3.43±2.88） scores， the difference before and after daily activity score was （12.37±10.21） scores， and the total score before and after treatment was （17.48±12.76） scores， which were also higher than those in the control group （2.82±3.29）， （10.80±9.63），（14.82±12.62） scores. The results of comparing the improvement of other symptoms before and after treatment showed that the improvement rate of less sleep and more dreams in the observation group was 28.3%（17/60）， which was significantly higher than that of the control group of 2.2%（1/45）（χ²=5.914，P<0.05）， and the improvement rates of the five symptoms of thirst and drinking， irritability， dry mouth and pharynx， dull complexion and hand， foot and mouth fever in the observation group were 3.3%（2/60）， 10.0%（6/60）， 8.3%（5/60）， 10.0%（6/60） and 5.0%（3/60）， respectively， which were higher than those in the control group -2.2%（1/45）， 2.2%（1/45）， 2.2%（1/45）， 4.5%（2/45）， -6.7%（3/45）. Through network analysis， it was found that the enrichment pathway of Henggu bone wound healing agent mainly acted on the three mechanisms of bone improvement， energy metabolism and anti-inflammatory and analgesic， and the sodium hyaluronate enrichment pathway mainly acted on the anti-inflammatory and analgesic mechanism. ConclusionThe efficacy of Osteoking combined with intra-articular injection of sodium hyaluronate in the treatment of patients with knee osteoarthritis in attack and remission is better than that of sodium hyaluronate alone， especially in anti-inflammatory and analgesic， and the two drugs have synergistic effect. Osteoking may play its role in relieving the symptoms of joint stiffness， tingling， heat pain， and less sleep and more dreams by improving bone quality and regulating the body's energy metabolism pathways， which is worthy of clinical promotion.

ObjectiveTo explore the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis based on real-world data and provide a basis for clinical medication. MethodFrom May 2020 to December 2021， the data of a total of 1 002 patients with knee osteoarthritis who did not undergo knee joint replacement surgery was collected through the registration method. 952 patients were ultimately included， including 133 cases orally taking Osteoking combined with non-steroidal anti-inflammatory drugs as the observation group and 73 cases orally taking non-steroidal anti-inflammatory drugs alone as the control group. Statistical analysis was conducted on the baseline data， VAS scores， WOMAC scores， and other items. The visit point is the 4^th and 8^th weeks after registration. In order to further elucidate the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis， the effective components of Osteoking and the relevant gene sets of non-steroidal anti-inflammatory drugs and knee osteoarthritis were obtained through network pharmacology methods and retrieval in bone injury cross database， TCMSP， and other databases. Venn analysis was performed on the relevant gene sets， and a PPI network diagram was constructed. Then key core targets were screened out， and enrichment GO and KEGG enrichment analyses were conducted. ResultThe VAS score of the observation group decreases by an average of （-2.79±1.206） scores in the 4^th week， which is better than the control group ［（-2.73±1.575） scores， P<0.05］. The VAS score of the observation group decreases by an average of （-3.97±1.308） scores in the 8^th week， which is better than the control group ［（-3.89±1.822） scores， P<0.05］. The total WOMAC score of the observation group decreases by an average of （-52.07±21.677） scores points in the 8^th week， which is significantly better than the control group ［（-46.75±25.368） scores， P<0.05］. The observation group has an average decrease of （-10.99±4.229） scores in WOMAC （pain） score in the 8^th week， which is better than the control group ［（-10.03±5.535） scores， P<0.05］. The observation group has an average decrease of （-1.49±2.901） in WOMAC （stiffness） score in the 4^th week， which is better than the control group ［（-0.92±1.998） scores， P<0.05］， and the observation group has an average decrease of （-1.90±3.200） scores in WOMAC （stiffness） score in the 8^th week， which is better than the control group ［（-1.26±2.230） scores， P<0.05］. The observation group shows an average decrease of （-39.17±16.562） scores in WOMAC （joint function） score in the 8^th week， which is significantly better than the control group ［（-35.47±20.098） scores， P<0.05］. According to network pharmacology analysis， the core network target of Osteoking in treating knee osteoarthritis is manifested as regulating signal pathways such as signal transduction transcription activator 3（STAT3）， vascular endothelial growth factor A（VEGFA）， tumor necrosis factor （TNF） to regulate cell signaling， angiogenesis， chondrocyte proliferation and migration， and inflammatory cells， thereby inhibiting inflammatory reactions， reducing damage， and delaying the development of the disease. ConclusionAfter a 4-week and 8-week course of treatment for knee osteoarthritis with Osteoking combined with non-steroidal anti-inflammatory drugs， there is a significant therapeutic effect on relieving pain and joint stiffness and improving joint function. In network pharmacology， Osteoking is involved in regulating inflammatory factors， metabolic response-related biological processes， the proliferation and apoptosis of chondrocytes， etc. in the treatment of knee osteoarthritis， resulting in anti-inflammatory and analgesic effects and improving joint mobility and joint stiffness. Therefore， it is worthy of clinical promotion and application.

Objective: To explore the osteogenic activity of Zn/Ca/P-containing coatings on titanium implant surface modified by plasma electrolytic oxidation (PEO). Methods: Three groups implants including Zn/Ca/P-containing surface treated by PEO in experimental groups and Ca/P-containing and TiO₂ sandblasted surface in control group were randomly inserted in the bilateral mandibular of rabbits. Mechanical testing and implant-bone interface observation were performed at 4, 6, 8, 10 and 12 weeks after implantion. Results: Zn/Ca/P-containing coating presented a microporous structure. The push-out value indicated the statistical differences among the three groups at each observed time point (P<0.05), and implant-bone bonding power reached a maximum value at 12 weeks, those in the Zn/Ca/P-containing group [(1.57±0.26) MPa] was higher than those in the group with sandblasted surface [(0.83±0.24) MPa] (P<0.05). Histological examination and implant-bone interface observation using field scaning electron microscope (FSEM) showed that the new bone of implant-bone interface increased with healing time and the result from Zn/Ca/P-containing group was superior to that from the control groups at each observed time point. Conclusions Zn/Ca/P-containing coatings by PEO can accelerate bone formation and remodeling, and enhance bone-implant bonding force.

OBJECTIVE: To optimize the method for embedding multiple undecalcified mouse tibias in plastic blocks, improve the efficiency and stability of plastic embedding and reduce the detachment rate of plastic slides. METHODS: Thirty undecalcified tibias from 15 B6 mice were used for plastic embedding after calcein labeling, fixation, dehydration and infiltration. The tibias were embedded in cylindrical plastic blocks with a diameter of 4 mm. For each bone, the 1/4 proximal tibia was cut off, and the remaining 3/4 was used for re-embedding. Five bones were embedded in a single block with each bone standing closely on the surface of a flat plate. The samples were randomized into control and experimental groups in all the processes of embedding, sectioning and staining. In the 3 groups with modified embedment, flowing CO was added into the embedding solution, embedding solution was applied to the section surface, and the slides were heated at 95 ℃ for 15 min. The polymerization time, slide detachment rate, bone formation and osteoblast parameters were analyzed. RESULTS: We prepared 6 plastic blocks, each containing 5 tibias, whose cross sections were on the same plane. The blocks were completely polymerized and suitable for sectioning. Flowing CO into the embedding solution reduced the polymerization time and increased the rate of complete polymerization. Application of the embedding solution on the section surface significantly reduced the detachment rate of the sections ( < 0.05) without affecting bone formation analysis ( > 0.05). Heating the slides significantly lowered the detachment rate of the sections ( < 0.05) without affecting osteoblast analysis ( > 0.05). CONCLUSIONS The optimized method allows effective embedding of multiple undecalcified mice tibias in the same block and can be an ideal method for histological analysis of undecalcified bones.
Animals ; Mice ; Plastics ; Staining and Labeling ; Tibia ; Tissue Embedding ; methods

Objective To study the association of maternal calcium supplementation and dietary calcium intake with the preterm birth so that to provide scientific basis for effective intervention of preterm birth. Methods Normal pregnant women who were followed up all through to childbirth in Gansu Provincial Maternity and Child Care Hospital were selected. Multivariate logistic regression was used to evaluate the associ-ation of calcium supplementation and intake with preterm birth. Results After confounding factors were adjus-ted, pregnant women who took calcium supplement for more than 3 months before and/or during pregnancy had the risk of preterm birth reduced by 14% which was dose-responding ( OR=0. 86, 95% CI=0. 77-0. 96, P<0. 05). Through stratifying by trimesters of pregnancy, it was found that calcium supplement in the third trimes-ter was a protective factor for preterm birth and especially significant in early and very early pregnancy ( OR=0. 75, 95% CI=0. 62-0. 92, P<0. 05). Through stratifying by dietary calcium intake, pregnant women who took dietary calcium more than 465. 55 mg/d had the risk of preterm birth significantly reduced which was shown by the reduction of preterm birth of different degrees, controlled preterm labor and spontaneous premature dilivery (OR=0. 66, 95% CI=0. 53-0. 82, P<0. 05). Conclusion Appropriate calcium supplementation or dietary calcium intake before and during pregnancy can reduce the risk of preterm birth, which is especially sig-nificant in late pregnancy.

Objective To evaluate the implant-bone interfaces on implants with active Zn coating in a rabbit model.Methods Pure titanium cylinder implants,fabricated by machining,were prepared by surface microarc oxidation (MAO).The MAO-Zn/Ca/P coated (experimental group) and the MAO-Ca/P coated (control group)implants were randomly placed in the rabbit mandible.The samples were harvested at 4 and 12 weeks postoperatively,histological analysis on the implant-bone interfaces of the two implants was performed,and the bone coverage was compared.Results The coatings of MAO presented micro-porous structure with dense and uniform features,in which size of micro-porous increased with zinc element.The histological examination of implant-bone contact interfaces showed that the bone tissues attached on the coatings increased with time.Further,the adhered bone tissue in the experimental group was thicker and denser and had a larger amount compared to that in the control group at 4 and 12 weeks postoperatively.The bone coverage in the experimental group (70.8％±13.6％) at 12 weeks postoperatively was significantly higher than that in the control group (55.9％±13.8％) (P＜0.05).The results of bone interface element showed that the apatite layer was precipitated at 12 weeks.Conclusion The addition of active zinc element can improve the biological activity of the coating,enhance the osteogenesis ability of the coating,and accelerate the osseointegration of implant-bone interfaces.

Objective To observe the therapeutic effect of acupoint injection with nucleotide plus conventional western medicine treatment for moderate and severe chronic obstructive pulmonary disease (COPD).Methods Sixty patients confirmed as moderate and severe COPD were evenly randomized into treatment group and control group.The treatment group was given conventional western medicine treatment and injection with nucleotide on bilateral Dingchuan points,and the control group was given conventional western medicine treatment alone.The treatment lasted for one year.The frequency of COPD acute onset and hospitalization times within one year were recorded.Meanwhile,the severity of dyspnea was evaluated with Medical Research Council (MRC) dyspnea scale scoring.Results (1)The frequency of COPD acute onset and hospitalization times within one year in the treatment group were lowered,and the differences were significant compared with those in the control group (P ＜ 0.05 or P ＜ 0.01).(2) After treatment,MRC dyspnea scale scores in the treatment group were improved (P ＜ 0.05 compared with those before treatment),but the improvement of the scores was insignificant in the control group(P ＞ 0.05).The intergroup comparison showed that the effect on improving MRC dyspnea scale scores in the treatment group was superior to that in the control group (P ＜ 0.05),indicating that the severity of dyspnea was much improved in the treatment group as compared with the control group.Conclusion Acupoint injection with nucleotide is effective on enhancing the therapeutic effect of conventional western medicine treatment for moderate and severe COPD.