Osteoporosis is a common bone disease， whose incidence is still on the rise， posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress， inflammatory response， and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation， oxidative stress， etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB （NF-κB） ligand （RANKL） pathway， osteoprotegerin （OPG） pathway， Wnt/β-catenin pathway， NF-κB pathway， mitogen-activated protein kinase （MAPK） pathway， adenosine monophosphate （AMP）-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway， and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine， aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

In this study, doxorubicin (DOX) was used as the model drug, new indocyanine green (IR820) as the photosensitizer, and temperature sensitive liposomes (TSL) as the carrier. H460-NCI photoheat-sensitive liposomes coated with cell membrane of human cell lung cancer (DOX-IR820-TSL@CCM) for highly effective multi-pathway tumor targeting in chemical-photothermal therapy and photodynamic therapy. DOX-IR820-TSL was prepared by reverse evaporation, cancer cell membrane (CCM) was prepared by lysis, crushing and centrifugation, and DOX-IR820-TSL@CCM was prepared by nanomembrane extrusion. The drug-loading conditions of DOX-IR820-TSL were finally determined: the ratio of organic phase to aqueous phase was 4.02, the dosage of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was 10.04 mg, and the lipid ratio was 0.12, and the significant phase transition temperature (T_m) of DOX-IR820-TSL was 43.05 ℃. The average particle size of DOX-IR820-TSL@CCM was 153.4 nm, the PDI was 0.279, and the zeta potential was -26.2 mV. The transmission electron microscope (TEM) image shows a homogeneous spherical structure and a translucent film layer. Under near-infrared irradiation, the drug release rate reaches 63.98%, which has adjustable photothermal conversion capacity and the ability to generate reactive oxygen species. Through SDS-PAGE electrophoresis, Western blot, cytotoxicity experiments and cell uptake experiments, it was proved that the design of cell membrane coating can well retain CD47, N-cadherin, CD44, CD326 and other related functional proteins, so that DOX-IR820-TSL@CCM has good immune evasion, homologous adhesion and homologous targeting. In this paper, DOX-IR820-TSL@CCM with camouflage properties and tumor targeting properties were successfully prepared, which can be used as a promising synergistic therapeutic diagnostic platform for future lung cancer treatment. All animal research programs have been approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine (number: 2022121011).

Objective To explore the association between R611H(G/A,rs734312)variation of WFS1 gene and early-onset type 2 diabetes mellitus(T2DM).Methods A total of 181 Chinese patients with early-onset T2DM(T2DM group)and 196 non-diabetic controls(NC group)were enrolled in this study.The rs734312 variation was detected by PCR-direct sequencing.Genotypic and allelic frequencies of rs734312 and clinical variables were compared and analyzed between the two groups.Results Compared with the NC group,the frequencies of AA genotype and A allele in R611H(G→A)variation were significantly elevated in the early-onset T2DM group,AA vs GA+GG(OR 1.720,95%CI 1.100～2.680,P<0.05).A vs G(OR 1.500,95%CI 1.020～2.220,P<0.05).The remarkable differences of frequencies of genotype and allele in rs734312(G/A)were observed between Asians(China,Japan and Korea)and Caucasians(Denmark,Britain,Spain,France and Russia,P<0.01 for each).Compared with AA genotype,fasting and 2 hours postprandial insulin(FIns and 2 hIns)as well as HOMA-β were significantly rise in GG+GA genotype carriers of early-onset T2DM group(P<0.05).Conclusions The a allele of rs734312 in WFS1 may be a risk factor for early-onset T2DM in Chinese population,and the variation might be a potential genetic marker for predicting the islet β-cell dysfunction in early-onset T2DM in Chinese population.

Objective:To investigate the mechanism of polygonatum and astragalus compound(PA)in inhibiting the progression of lung adenocarcinoma. Methods:CCK-8 assay was used to assess the inhibitory rate of proliferation in A549 and H1299 cells treated with PA at different concentrations and to calculate the half maximal inhibitory concentration(IC50).C57BL/6 mice(KRASG12D/+;TP53flox/flox)were treated with adenovirus carrying Cre enzyme via nasal inhalation to establish a mouse model of primary lung adenocarcinoma.The model mice were fed with PA-containing diet to directly observe the effect of PA on the lung adenocarcinoma tissue.Immunohistochemical staining was used to examine the pathological status of the lung tissue.Bioinformatics analysis indicated that PA affects the progression of lung adenocarcinoma through the apelin-peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α)-mitochondrial brown fat uncoupling protein 1(UCP1).Real-time quantitative PCR and Western blotting analysis were used to study the effect of PA on the mRNA and protein expression levels of apelin-PGC1α-UCP1 signaling pathway related genes.An ATP detection kit and flow cytometry were used to evaluate the effect of PA on the ATP and mitochondrial ROS production,respectively,in A549 and H1299 cells.siUCP1 was used to silent the expression of UCP1 while Z160 was used to induce UCP1 overexpression in A549 and H1299 cells,and the changes in ATP and mitochondrial ROS production were examined to further investigate whether PA acts on apelin-PGC1α-UCP1 signaling pathway to affect the progression of lung adenocarcinoma. Results:PA could obviously inhibit the proliferation of A549 and H1299 cells with the IC50 values of 10.66 mg/mL for A549 cells and 9.66 mg/mL for H1299 cells.In the mouse primary lung adenocarcinoma model,PA could effectively inhibit the growth of tumor,downregulate apelin-PGC1α-UCP1 signaling pathway and inhibit the expression of lung adenocarcinoma-promoting gene UCP1.In A549 and H1299 cells,PA could significantly inhibit the expression of apelin,PGC1α and UCP1(P＜0.05),promote the production of ATP(P＜0.000 1)and ROS,restore mitochondrial oxidative phosphorylation,and inhibit aerobic glycolysis(P＜0.01).UCP1 silencing could increase the production of ATP(P＜0.01)and mitochondrial ROS and decrease the expression of key glycolysis enzymes hexokinase 2(HK2)and pyruvate kinase isozyme type M2(PKM2)(P＜0.05).Increasing the expression of UCP1 could reduce the ATP production(P＜0.01)and mitochondrial ROS generation in cells while increase the expression of HK2 and PKM2(P＜0.05).Treating cells with PA and Z160 simultaneously(PA+Z160)could reverse the inhibitory effect of PA on the ATP production and glycolysis of tumor cells(P＜0.05). Conclusion:PA can downregulate the apelin-PGC1α-UCP1 signaling pathway,inhibit mitochondrial uncoupling,restore mitochondrial oxidative phosphorylation,inhibit aerobic glycolysis,reverse the Warburg effect,and thus inhibit lung adenocarcinoma progression.

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --^SEA, followed by 5.70% for -α^3.7, and 0.24% for --^Thai. Among 32 α-thalassemia genotypes, the most common five were --^SEA/αα, -α^3.7/αα, α^CSα/αα, -α^4.2/αα and α^WSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --^Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --^SEA/αα, -α^3.7/αα combining CD41-42/N and --^SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --^SEA/-α^3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α^3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of α^WSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --^SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --^SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --^Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Dipeptidyl Peptidase 4/genetics* ; China/epidemiology* ; Genotype ; Mutation

OBJECTIVE: To investigate the detection rate and hematologic phenotype of HKαα thalassemia in south Guangxi, in order to provide reference for the prevention and control of thalassemia and prenatal and postnatal care consultation in this region. METHODS: Gene testing was performed on pre-marital medical examinations, pre-pregnancy eugenic health examinations, prenatal examinations and hospitalized thalassemia-positive persons in south of Guangxi, and the results were analyzed. RESULTS: A total of 183 190 thalassemia patients were included in this study, the age was mainly concentrated in 26-35 years old (101 709 cases, accounting for 55.521%), and 40 HKαα mutations were detected, detection rate was 0.022%, including 5 cases in Nanning, 22 cases in Qinzhou, 2 cases in Fangchenggang, 11 cases in Beihai. A total of 29 ethnic groups were included in the survey, but HKαα gene was observed only in Han nationality (0.0380%) and Zhuang nationality (0.0068%). A total of 8 genotypes carrying HKαα mutations were detected in this study ( HKαα/--^SEA, β^N/ β^N, HKαα/αα, β^-28/ β^N, HKαα/αα, β^-50/ β^N, HKαα/αα, β^CD17/ β^N, HKαα/αα, β^CD27/28/β ^N, HKαα/αα, β^CD41-42/ β^N, HKαα/αα, β^CD71-72/ β^N, and HKαα/αα, β^N/ β^N). Except for most cases with HKαα/αα, β^N/ β^N genotypes with no significant changes in the hematological indexes, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) of other genotypes were decreased, showing microcytic hypochromic performance, mild anemia or no anemia. CONCLUSION HKαα carrier is often misdiagnosed as -α^3.7 carrier, which easily leads to missed diagnosis or misdiagnosis. Therefore, it is necessary to continuously improve the diagnostic level of laboratory testing personnels and genetic counselors to avoid unnecessary interventional puncture operations and birth of children with moderate and severe thalassemia.
Child ; Female ; Pregnancy ; Humans ; Adult ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; China ; Genotype ; Phenotype ; Mutation

Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.
Humans ; Prognosis ; Osteosarcoma/genetics* ; Immunotherapy ; Macrophages ; Transcription Factors ; Bone Neoplasms/genetics* ; Homeodomain Proteins ; Repressor Proteins