Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

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.

BACKGROUND:Zinc-based alloy medical implant materials have excellent mechanical properties,complete degradability and good biocompatibility,and are mainly used in orthopedic implants,cardiovascular stents,bile duct stents,tracheal stents,nerve catheters,etc. OBJECTIVE:To review the research progress of biodegradable zinc-based alloys in bone defect repair and prospect the promising research direction and achievements of zinc-based materials. METHODS:After searching PubMed,Web of Science,WanFang Data,and CNKI databases from the establishment of the database to June 2023,various relevant articles on biodegradable zinc-based alloys for bone implant material research were collected.The basic characteristics of biodegradable zinc based alloys were summarized,and the role of zinc-based alloys in promoting bone tissue repair was sorted and summarized.The current research hotspots and shortcomings were discussed. RESULTS AND CONCLUSION:(1)Zinc-based alloys have good biocompatibility.Using zinc-based alloys as the matrix material,with the help of scaffold structure construction technology and coating optimization process,the bone conductivity of zinc-based alloys will be effectively improved,and their degradation products will have efficient bone induction to regulate the gene expression of osteoblasts and osteoclasts,thereby promoting the repair and reconstruction of bone defects.(2)However,in the research on optimizing zinc-based alloys,the coating process is relatively insufficient,and additive loading technology is still lacking.(3)Zinc-based alloys have excellent mechanical and biological properties.Through special processes,their bone conductivity and osteoinductivity can be increased to effectively improve their ability to promote bone repair and reconstruction,and it is expected to further achieve the development of personalized transplant materials.Further research and development are needed to optimize the integration of coating and additive loading technologies into zinc-based alloys.

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

OBJECTIVES: To investigate the role and mechanism of fibroblast growth factor (FGF) 19 in inflammation-induced injury of vascular endothelial cells caused by high glucose (HG). METHODS: Human umbilical vein endothelial cells (HUVECs) were randomly divided into four groups: control, HG, FGF19, and HG+FGF19 (n=3 each). The effect of different concentrations of glucose and/or FGF19 on HUVEC viability was assessed using the CCK8 assay. Flow cytometry was utilized to examine the impact of FGF19 on HUVEC apoptosis. Levels of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured by ELISA. Real-time quantitative PCR and Western blotting were used to determine the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2 related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Cells were further divided into control, siRNA-Nrf2 (siNrf2), HG, HG+FGF19, HG+FGF19+negative control, and HG+FGF19+siNrf2 groups (n=3 each) to observe the effect of FGF19 on oxidative stress injury in HUVECs induced by high glucose after silencing the Nrf2 gene. RESULTS: Compared to the control group, the HG group exhibited increased apoptosis rate, increased IL-6, iNOS and MDA levels, and increased VEGF mRNA and protein expression, along with decreased T-SOD activity and decreased mRNA and protein expression of Nrf2 and HO-1 (P<0.05). Compared to the HG group, the HG+FGF19 group showed reduced apoptosis rate, decreased IL-6, iNOS and MDA levels, and decreased VEGF mRNA and protein expression, with increased T-SOD activity and increased Nrf2 and HO-1 mRNA and protein expression (P<0.05). Compared to the HG+FGF19+negative control group, the HG+FGF19+siNrf2 group had decreased T-SOD activity and increased MDA levels (P<0.05). CONCLUSIONS FGF19 can alleviate inflammation-induced injury in vascular endothelial cells caused by HG, potentially through the Nrf2/HO-1 signaling pathway.
Humans ; NF-E2-Related Factor 2/genetics* ; Signal Transduction ; Human Umbilical Vein Endothelial Cells/drug effects* ; Fibroblast Growth Factors/pharmacology* ; Heme Oxygenase-1/physiology* ; Apoptosis/drug effects* ; Glucose ; Inflammation ; Interleukin-6/analysis* ; Vascular Endothelial Growth Factor A/genetics* ; Nitric Oxide Synthase Type II/analysis* ; Cells, Cultured

OBJECTIVE: To explore the construction method of a resistant multiple myeloma (MM) patient-derived xenotransplantation (PDX) model. METHODS: 1.0×10⁷ MM patient-derived mononuclear cells (MNCs), 2.0×10⁶ MM.1S cells and 2.0×10⁶ NCI-H929 cells were respectively subcutaneously inoculated into NOD.CB17-Prkdc^scid Il2rg^tm1/Bcgen (B-NDG) mice with a volume of 100 μl per mouse to establish mouse model. The morphologic, phenotypic, proliferative and genetic characteristics of PDX tumor were studied by hematoxylin-eosin staining, immunohistochemical staining (IHC), cell cycle analysis, flow cytometry and fluorescence in situ hybridization (FISH). The sensitivity of PDX tumor to bortezomib and anlotinib monotherapy or in combination was investigated through cell proliferation, apoptosis and in vitro and in vivo experiments. The effects of anlotinib therapy on tumor blood vessel and cell apoptosis were analyzed by IHC, TUNEL staining and confocal fluorescence microscope. RESULTS: MM PDX model was successfully established by subcutaneously inoculating primary MNCs. The morphologic features of tumor cells from MM PDX model were similar to those of mature plasma cells. MM PDX tumor cells positively expressed CD138 and CD38, which presented 1q21 amplification, deletion of Rb1 and IgH rearrangement, and had a lower proliferative activity than MM cell lines. in vitro, PDX, MM.1S and NCI-H929 cells were treated by bortezomib and anlotinib for 24 hours, respectively. Cell viability assay showed that the IC₅₀ value of bortezomib were 5 716.486, 1.025 and 2.775 nmol/L, and IC₅₀ value of anlotinib were 5 5107.337, 0.706 and 5.13 μmol/L, respectively. Anlotinib treatment increased the apoptosis of MM.1S cells (P < 0.01), but did not affect PDX tumor cells (P >0.05). in vivo, there was no significant difference in PDX tumor growth between bortezomib monotherapy group and control group (P >0.05), while both anlotinib monotherapy and anlotinib combined with bortezomib effectively inhibited PDX tumor growth (both P < 0.05). The vascular perfusion and vascular density of PDX tumor were decreased in anlotinib treatment group (both P < 0.01). The apoptotic cells in anlotinib treatment group were increased compared with those in control group (P < 0.05). CONCLUSION Bortezomib-resistant MM PDX model can be successfully established by subcutaneous inoculation of MNCs from MM patients in B-NDG mice. This PDX model, which retains the basic biological characteristics of MM cells, can be used to study the novel therapies.
Animals ; Bortezomib ; Humans ; Multiple Myeloma/pathology* ; Mice ; Apoptosis ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Mice, Inbred NOD ; Disease Models, Animal ; Cell Proliferation ; Transplantation, Heterologous

OBJECTIVE: To analyze the laboratory detection results of hemolytic disease of the fetus and newborn(HDFN). METHODS: Related test results of 283 newborns and their mothers' blood samples from Kunming Maternal and Child Health Hospital from August 2023 to May 2024 were collected, including mother and child ABO blood group, RhD blood group, as well as 3 tests of HDFN, total bilirubin (TBil) and indirect bilirubin (IBil). RESULTS: 283 were ABO incompatibility, among which 187 were HDFN positive, with a positive rate of 66.08%; the positive rate of HDFN in neonates with antigen-A incompatibility was 74.12%(126/170), the positive rate of HDFN in neonates with antigen-B incompatibility was 53.57%(60/112), which was the highest in neonates with O/A incompatibility ［75.45%(126/167)］, followed by O/B incompatibility［54.55%(60/110)］. Group by age, the positive rates of HDFN in the ≤1 d group, 2 d group, 3 d group, 4 d group, 5 d group and ≥6 d group were 76.03%(111/146), 67.86%(38/56), 57.14%(24/42), 38.46%(5/13), 46.15%(6/13) and 23.08%(3/13), respectively. With the increase of age, the positive rates of HDFN gradually decreased, there was a statistically significant difference between the ≤3 day age group and >3 day age group ( P <0.05). There was no statistically significant difference in TBil and IBil levels between the "direct antibody+indirect antibody+release+" group and the HDFN negative group in newborns. HDFN infants exhibited a rapid increase in bilirubin levels within the first day after birth, with significantly higher TBil and IBil values compared to Non ABO-HDFN infants in the ≤1 day group ( P <0.01). However, the difference of bilirubin levels between the two groups gradually narrowed from 2-6 days after birth, and the difference was not statistically significant (P >0.05). The peak value of TBil and IBil occurred on the 4th day after birth in HDFN infants. CONCLUSION ABO-HDFN is most commonly seen in newborns whose mothers are type-O, and the positive rate was the highest in newborns with O/A incompatibility. The detection rate of HDFN is affected by the age of the newborns, and the two were correlated inversely. ABO-HDFN group developed more rapidly with a higher peak. Therefore, HDFN tests should be carried out as soon as possible for mothers and newborns with incompatible blood types, and appropriate treatment should be provided to prevent complications.
Humans ; Infant, Newborn ; ABO Blood-Group System ; Erythroblastosis, Fetal/epidemiology* ; Female ; China/epidemiology* ; Blood Group Incompatibility ; Male ; Bilirubin/blood*

OBJECTIVE: To explore the significance of thrombus biomarkers in evaluating the progression of immunoglobulin A vasculitis (IgAV) in children. METHODS: A total of 193 children who were diagnosed as IgAV from September 2021 to June 2023 in the Children's Hospital of Soochow University were enrolled. The levels of plasma thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) and D-dimer (D-D) were analyzed retrospectively. And, 140 healthy children were selected as controls during the same period. The receiver operating characteristic (ROC) curves were drawn to analyze the role of thrombus parameters in estimating the progression of IgAV in children. Univariate and multivariate logistic regression analysis were used to assess the independent risk factors influencing the progression of pediatric IgAV in acute phase. RESULTS: The levels of D-D, TAT, PIC and t-PAIC in plasma of IgAV group were higher than those in control group (all P <0.001). The levels of D-D, TAT and PIC in acute phase children were significantly higher than those in non acute phase children (all P <0.001), while the levels of kidney injury related indicators such as 24h-UTP, urine albumin/creatinine ratio, positive urinary blood on dipstick, serum creatinine and cystatin C were lower (all P <0.05). ROC analysis showed that the area under curve (AUC) of PIC was 0.743 when the cut-off value was 0.93 μg/ml with 71.8% sensitivity and 78.3% specificity, while the AUC of D-D was 0.756 when the cut-off value was 550.0 μg/L with 81.3% sensitivity and 73.4% specificity. Univariate and multivariate logistic regression analysis showed that PIC≥0.93 μg/ml (OR =4.64, P =0.012) and D-D≥550.0 μg/L (OR =3.60, P =0.035) were the independent risk factors for the progression of IgAV in acute phase. CONCLUSION The pediatric patients with IgAV have shown hyperfibrinolysis in the acute stage. Furthermore, the levels of PIC and D-D should be of diagnostic value for evaluating the progression of IgAV in the acute phase.
Humans ; Biomarkers/blood* ; Child ; Fibrin Fibrinogen Degradation Products ; Retrospective Studies ; Thrombosis ; Female ; Male ; Disease Progression ; Thrombomodulin/blood* ; ROC Curve ; Vasculitis/blood* ; Antithrombin III ; Plasminogen Activator Inhibitor 1/blood* ; IgA Vasculitis/blood* ; alpha-2-Antiplasmin ; Adolescent ; Child, Preschool ; Fibrinolysin

OBJECTIVE To conduct a rapid and comprehensive evaluation of commonly used oral dihydropyridine calcium channel blockers （DHP CCBs） in Guangxi， and provide scientific basis for clinical medication and drug selection in medical institutions. METHODS Based on the actual drug use data of public medical institutions at the second level and above in Guangxi Zhuang Autonomous Region， and based on the national centralized collection catalog， commonly used oral DHP CCBs were selected. The Professional Committee of Evidence-based Pharmacy of the Guangxi Pharmaceutical Association organized relevant experts from multiple medical institutions in the region to conduct a quantitative scoring of the selected oral DHP CCBs from five key dimensions of pharmaceutical characteristics， effectiveness， safety， economy， and other attributes， by referring to the Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions （the Second Edition）， combined with the latest evidence-based medical research results， and widely soliciting suggestions from clinical and pharmaceutical experts. Finally， the Guangxi Expert Consensus on Rapid Comprehensive Evaluation of Oral Dihydropyridine Calcium Channel Blockers in the Treatment of Cardiovascular Disease was formulated. RESULTS A total of 30 commonly used oral DHP CCBs were selected. Among them， Amlodipine besylate tablets （Huizhi） demonstrated superior comprehensive performance （81.79 points）， excelling particularly in pharmaceutical properties， effectiveness and other attributes. The compound scores of Amlodipine besylate tablets （Chongqing Yaoyou） and Amlodipine besylate tablets （Suzhou Dongrui） ranked second and third respectively， with scores of 81.66 and 81.60 points. CONCLUSIONS This consensus can provide guidance and decision-making support for the rational clinical application of oral DHP CCBs in Guangxi Region and the selection of drug directories in medical institutions.

Periodontitis is a chronic inflammatory disease of the periodontal supporting tissues caused by plaque microorganisms, whereas inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by gastrointestinal tract damage. Studies have revealed a close association between periodontitis and IBD, and gut microbiota has been shown to play an important role in the development of IBD. When the gut microbiota is disturbed, it leads to intestinal barrier disruption, triggers immune-inflammatory responses, and influences IBD progression. There are significant differences between the salivary microbiota of periodontitis patients and healthy individuals, and periodontal pathogens can enter the intestinal tract with saliva and participate in the development of IBD by influencing the interactions between gut microbiota composition, immune responses, metabolite production, and intestinal barrier function. Current gut microbiota-targeted intervention strategies, such as fecal microbiota transplantation (FMT) and probiotic supplementation, have shown potential therapeutic value in the treatment of periodontitis. These approaches may exert synergistic effects on both periodontitis and IBD through microbiota modulation. This review summarizes research progress on the relationship between periodontitis and IBD to provide a foundation for the prevention and treatment of these two diseases.