ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

BACKGROUND:Acupoint embedding and floating needle therapy are two methods for the treatment of knee osteoarthritis,but there are few reports on the combined treatment of the two methods. OBJECTIVE:To investigate the therapeutic effect of acupoint embedding combined with floating needle therapy on different stages of knee osteoarthritis using generalized estimating equations. METHODS:A total of 436 patients with knee osteoarthritis admitted to Dongguan Hospital of Traditional Chinese Medicine from February 2019 to February 2023 were selected as the research subjects.All patients were randomly divided into a control group with floating needle therapy(n=218)and an observation group with acupoint embedding method combined with floating needle therapy(n=218).Staging was performed according to the K-L staging method.In the control group,there were 57 cases in stage Ⅰ,62 in stage Ⅱ,49 in phase Ⅲ,and 50 in stage Ⅳ,while in the observation group,there were 48 cases in stage Ⅰ,66 in stage Ⅱ,63 in phase Ⅲ,and 41 in stage Ⅳ.The levels of indexes and clinical efficacy were compared between groups before and after treatment.Generalized estimating equation model was used to analyze the influencing factors of clinical efficacy and the interaction effect of different time points,different methods and different stages on therapeutic efficacy. RESULTS AND CONCLUSION:There was no significant difference in baseline data between the observation group and the control group,as well as between the patients of different stages(P>0.05).After treatment,the cure rate of stage Ⅰ patients was the highest after treatment,and the total improvement rate in the observation group was significantly higher than that in the control group.There were significant differences in the cure rate among different stages in each group(P<0.05).After treatment,all indicators in the two groups were significantly decreased.In the control group,there were significant differences in various indicators of patients at different stages after 4 weeks of treatment(P<0.05).In the observation group,after 2 weeks of treatment,there were significant differences in various indicators of patients at different stages(P<0.05),and all the indexes in the observation were lower than those in the control group after 4 weeks of treatment(P<0.05)and the therapeutic effect in the observation group was better than that in the control group.Generalized estimating equation model analysis showed that trauma history,interleukin-6 level,treatment method,treatment time and K-L stage all significantly affected the clinical efficacy in patients.In the interaction effect analysis,after 2 weeks of treatment,there was a significant difference in the visual analogue scale score between the two groups in stages Ⅲ and Ⅳ(P<0.05).After 4 weeks of treatment,there was a significant difference in the visual analogue scale score between the two groups in stages Ⅱ,Ⅲ,and Ⅳ(P<0.05).To conclude,acupoint embedding combined with floating needle therapy is superior to floating needle therapy alone in the treatment of different stages of knee osteoarthritis.Trauma history,interleukin-6 level,treatment method,treatment time and K-L stage significantly influence the therapeutic effect.

BACKGROUND:Types II,IIA,and III of Hangman fractures often require surgical treatment,and the selection of surgical methods is controversial.Current surgeries have shortcomings such as incomplete reduction and malunion after surgery.In the early stage,our team used C2-3 lag screws combined with a bucking bar.Intermittent pushing of the C2 vertebral body in the oropharynx has achieved satisfactory clinical results.However,the preliminary studies included few samples and lacked a control group for comparison. OBJECTIVE:To compare the clinical efficacy of posterior C2-3 fixation combined with the bucking bar technique and posterior C2-3 fixation alone in the treatment of unstable Hangman fractures. METHODS:The clinical and imaging data of 55 patients with unstable Hangman fractures who underwent posterior C2-3 internal fixation in Affiliated Hospital of Southwest Medical University were retrospectively analyzed.According to the surgical plan,the patients were divided into two groups.Among them,23 patients received posterior cervical C2-3 internal fixation combined with the bucking bar technique(group A),and 32 patients received simple posterior C2-3 internal fixation(group B).Operation time,intraoperative blood loss,complications,pain visual analog scale score,neck disability index,American Spinal Injury Association classification,and patient satisfaction(Odom's classification)preoperation and during follow-up were compared between the two groups.The changes in C2-3 displacement and angulation and other imaging indicators were compared at each observation time point. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in operation time,intraoperative blood loss,and postoperative complications between the two groups(P>0.05).(2)The neck pain visual analog scale and neck disability index scores of the two groups of patients at the final follow-up were significantly improved compared with those before surgery(P<0.05).The Odom standard classification showed that 21 cases(91%)in group A were excellent and 29 cases(91%)were excellent and good in group B.There was no statistically significant difference in the clinical efficacy indicators between the two groups(all P>0.05).(3)There was no significant difference in C2-3 angulation and displacement between the two groups before operation(P>0.05).Postoperation and at the last follow-up,the angle and displacement of C2-3 in both groups were significantly smaller than before surgery,and the difference was statistically significant(P<0.01).There was no statistically significant difference in the above indicators after surgery and at the last follow-up(P>0.05).After surgery and at the last follow-up,the displacement and angle of C2-3 in group A were significantly smaller than those in group B(P<0.05).(4)At the last follow-up,no patients in group A had residual deformity,and 4 cases(13%,4/32)in group B had residual deformity.(5)Therefore,posterior C2-3 fixation combined with transoral bucking bar technology may be beneficial to the reduction and stabilization of the vertebral body,reduces malunion,and can achieve better reduction.

BACKGROUND:Metal-organic frameworks exhibited great potential for bone tissue engineering and bone disease treatment because of its unique merits including tunable porosity,a large specific surface area,good biocompatibility,and easy structure modification. OBJECTIVE:To review the advancements,application,strengths,and weaknesses of metal-organic framework materials in bone repair,arthritis,bone infection,and bone tumors,offering guidance and strategies for future research. METHODS:Web of Science,PubMed,and CNKI databases were searched using Chinese and English keywords"metal-organic frameworks,MOFs,orthopedics,bone repair,bone regeneration,orthopaedic applications,bone tissue engineering,bone infection,arthritis,bone tumor,osteosarcoma"for related literature published from 2015 to 2023.Following initial screening based on inclusion and exclusion criteria,72 articles were finally included for review. RESULTS AND CONCLUSION:(1)During bone repair,metal ions of metal-organic frameworks can induce bone formation by activating specific signaling pathways,which include stimulating osteogenic gene expression,inhibiting osteoclasts,encouraging blood vessel formation,and speeding up bone mineralization.Hence,metal-organic frameworks with metals like calcium,strontium,cobalt,copper,and magnesium ions show significant potential in enhancing bone implant performance.(2)Metal-organic framework materials,especially zinc/cobalt-based metal-organic frameworks,exhibit enzyme-like activities and promote cartilage regeneration by scavenging reactive oxygen species.Compared with natural enzymes,it has the advantages of not easy inactivation and better stability.(3)Zinc-based metal-organic framework materials characterized with wide band gaps,efficient separation and migration of photogenerated carriers,and high stability,the enhancement of photocatalytic activity results from enhancing the excited electron-hole widely used for the eradication of bacteria and tumor cells.(4)Bimetallic metal-organic frameworks,the doping of additional metals,showed critical advantages in optimizing structural performance,such as zinc/magnesium-based metal-organic framework 74 offering increased stability for durable antibacterial activity,and the light absorption capacity and photocatalytic efficiency of tantalum/zirconium-based metal-organic framework greatly improved and thus enhancing the radiation therapy.(5)However,metal-organic framework materials still face challenges in clinical applications,such as the uncertainty of drug release,in vivo safety,and potential immune responses from long-term presence.

The Chinese Pharmacopoeia is the legal technical standard which should be followed during the research, production, use, and administration of drugs. At present, the new edition of the Chinese Pharmacopoeia is planned to be promulgated and implemented. This article summarizes and analyzes the main characteristics and the content of updates and amendments of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅰ), to provide a reference for the correct understanding and accurate implementation the new edition of the pharmacopoeia.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Aromatic Chinese medicinal essential oils are volatile oils extracted from aromatic Chinese herbs， which can prevent and treat respiratory infectious diseases through multiple synergistic mechanisms including pathogen inhibition， immune regulation， and inflammatory response regulation. Essential oils are primarily used externally on the body to prevent infections and alleviate symptoms through methods like inhalation， smearing， topical application， bathing， gargling or as a suppository. They can also be utilized in the environment for disinfection and air purification， through methods like diffusion， vaporization， or spraying. The external application of essential oils extracted from Chinese aromatic herbs has the advantages of convenience， quick absorption， and simultaneous influence on both the body and mind. However， there are still challenges and deficiencies in aspects such as the positioning of functions， indications， safety， and the research on the mechanism of action. It has been proposed to combine the theory of aromatic Chinese medicinals with the characteristics of essential oils， and formulate prescriptions of Chinese medicinal essential oils under the principles of traditional Chinese medicine syndrome differentiation， and prevent and treat respiratory infectious diseases efficiently， accurately， and safely， thereby expanding the clinical application of aromatic Chinese medicinals and the preventive theory of traditional Chinese medicine.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.