PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

Low-intensity pulsed ultrasound (LIPUS) is a non-invasive sonodynamic therapy that has been approved by the U.S. Food and Drug Administration for clinical use. Clinical trials have demonstrated that LIPUS ameliorates mild-to-moderate erectile dysfunction without adverse events. Histological analysis of the corpus cavernosum suggests that the therapeutic benefits of LIPUS may be attributed to alleviation of fibrosis, enhanced neovascularization, and promotion of innervation. Further investigations have revealed that LIPUS facilitates cavernous tissue repair through non-thermal mechanisms, including a cavitation effect, acoustic streaming, mass transfer enhancement, and direct mechanical stimulation. Mechanobiological transduction triggers molecular signaling cascades within endogenous cavernous cells, thereby stimulating cell proliferation, angiogenesis, extracellular matrix remodeling, and stem cell differentiation. Although LIPUS has the potential to induce cavernous rehabilitation in the treatment of erectile dysfunction, further investigations are necessary to elucidate the mechanisms via which LIPUS regulates each type of cavernous cell to determine the optimal parameters for this innovative therapy.
Male ; Humans ; Erectile Dysfunction/therapy* ; Ultrasonic Therapy/methods* ; Penis/pathology* ; Ultrasonic Waves

OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

OBJECTIVE: To explore the effect of simvastatin monotherapy or in combination with doxorubicin on diffuse large B-cell lymphoma (DLBCL) cells and its possible molecular mechanisms. METHODS: The differences in the expression levels of genes and proteins related to the mevalonate (MVA) pathway between DLBCL tissues and reactive lymph node hyperplasia tissues were compared via database analysis, as well as their effects on the prognosis. CCK-8 assay was used to detect the effect of simvastatin and doxorubicin on the viability of different subtypes of DLBCL cells, EdU was used to detect cell proliferation, flow cytometry was used to detect apoptosis, and Western blot was used to detect related protein and signaling pathway proteins. RESULTS: The expression levels of MVA pathway-related genes were increased in tumor tissues of DLBCL patients through the TCGA database, and the median overall survival time of DLBCL patients in HMGCR high expression group was shorter (all P < 0.05). Meanwhile, according to The Human Protein Atlas database, HMGCR protein was significantly high expressed in DLBCL tumor tissue compared with normal tissue. The viability of DLBCL cell lines treated with simvastatin or doxorubicin monotherapy was decreased in time- and concentration-dependent manner, and could be further inhibited by simvastatin combined with doxorubicin especially in GCB subtype cell lines. Both simvastatin and doxorubicin could inhibit the proliferation of DLBCL cell lines, and their combination further suppressed dramatically. Both the two drugs promoted apoptosis in DLBCL cell lines, and the apoptosis was further increased after their combination. Compared with monotherapy, the expression of HMGCR protein and apoptosis-related protein Bcl-2 was further decreased but cleaved-caspase3 and Bax increased after combination therapy. Meanwhile, the expression level of phosphorylated proteins in PI3K-Akt pro-survival signaling pathway were decreased especially in GCB subtype cell lines. CONCLUSION HMGCR, the protein associated with cholesterol synthesis pathway, is highly expressed in DLBCL tumor tissues and indicates poor prognosis. Simvastatin, a lipid-lowering drug, combined with doxorubicin can further affect the survival of DLBCL tumor cells at the cellular level.
Humans ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; Doxorubicin/pharmacology* ; Simvastatin/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Signal Transduction ; Cell Line, Tumor ; Hydroxymethylglutaryl CoA Reductases/metabolism*

OBJECTIVE: To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province, and to analyze the genotypes and hematological phenotypes. METHODS: Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province, whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations. The mutations of β-globin gene clusters were confirmed by polymerase chain reaction (PCR) and Sanger DNA sequencing technology. RESULTS: The 3.5 kb deletion in β-globin gene cluster (NC_000011.10: g. 5224302-5227791del3490bp) was detected in 4 patients' samples, of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation. These 2 patients displayed moderate anemia phenotype, while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype. CONCLUSION Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia, compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia. In areas with a high incidence of thalassemia, suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.
Humans ; beta-Globins/genetics* ; Multigene Family ; beta-Thalassemia/genetics* ; Mutation ; Genotype ; Sequence Deletion ; Phenotype ; Male ; Female

OBJECTIVE: To investigate the efficacy and safety of combination regimen containing daratumumab in multiple myeloma (MM) patients. METHODS: The clinical data of 14 newly diagnosed MM patients and 58 relapsed refractory MM patients treated with combination regimen containing daratumumab from November 2020 to March 2023 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. The efficacy and safety of combination regimen were analyzed. RESULTS: The median age of the 72 patients was 62 (38-78) years, including 35 males and 37 females. The overall response rate (ORR) of patients receiving first-line, second-line, and third-line or above treatment was 92.9% (13/14), 68.2% (30/44), and 42.9% (6/14), respectively. The median progression-free survival (PFS) was not reached, 15.4 months, and 9.7 months in three groups, respectively (all P <0.05), while the median overall survival (OS) was all not reached. Among relapsed refractory patients, the ORR of those treated with DVd, DPd and DRd regimen was 50.0% (12/24), 40.0% (4/10) and 100% (10/10), the median PFS was 2.8 months, 10.3 months and not reached, and the median OS was 15.4 months, not reached and not reached, respectively. Furthermore, the PFS and OS in the DRd group were superior to those in the other two groups (all P <0.05). Cox univariate and multivariate analysis showed that lactate dehydrogenase (LDH) ≥250 U/L and extramedullary disease were independent adverse prognostic factors for PFS, and LDH ≥250 U/L was also an independent adverse prognostic factor for OS. Hematologic adverse reactions were mainly lymphopenia (87.5%) and thrombocytopenia (52.8%), while non-hematologic adverse reactions were mainly infusion-related reactions (19.4%) and infections (11.1%). CONCLUSIONS The combination regimens containing daratumumab can be used as first-line treatment for patients with newly diagnosed MM. In patients with relapsed refractory MM, early use of regimens containing daratumumab may improve treatment response rate and prolong PFS. The DRd regimen has better therapeutic response and survival advantages. LDH is an independent prognostic factor affecting PFS and OS in MM patients.
Humans ; Multiple Myeloma/drug therapy* ; Middle Aged ; Aged ; Male ; Female ; Antibodies, Monoclonal/administration & dosage* ; Adult ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To investigate the expression of CD19/CD73 in chronic lymphocytic leukemia (CLL) and its correlation with clinical features. METHODS: The clinical data of 60 CLL patients and 40 healthy volunteers (control group) from January 2022 to November 2023 were retrospectively analyzed. The levels of CD19 and CD73 in peripheral blood of CLL patients were measured by flow cytometry. Kaplan-Meier method was used for survival analysis. RESULTS: The hemoglobin (Hb) and CD19/CD73 levels in CLL group were significantly lower than those in control group, while CD19, CD73 and β₂-MG were significantly higher (all P <0.001). According to ROC curve analysis, the AUC value of CD19/CD73 for CLL diagnosis was 0.980 (95%CI : 0.949-1.000, P <0.05), the specificity was 92.50%, and the sensitivity was 98.30%. The CD19/CD73 level of CLL patients with splenomegaly was significantly lower than those without splenomegaly (P <0.01). There was no significant correlation between CD19/CD73 and Hb in CLL patients ( r =0.056, P >0.05). CD19/CD73 was positively correlated with β₂-MG ( r =0.837, 95%CI : 0.740 2-0.899 6, P <0.01). According to the median value (12.84) of CD19/CD73, the patients were divided into high and low expression groups. Kaplan-Meier survival analysis showed that the overall survival rate and progression-free survival rate at 18^th month in the low expression group were 87.08% and 93.25%, while those in the high expression group were 96.41% and 99.90%, respectively (both P <0.05). CONCLUSION The level of CD19/CD73 is low in CLL patients, which can be used as an auxiliary index for clinical diagnosis of CLL. CD19/CD73 is closely related to splenomegaly in CLL patients. Low expression of CD19/CD73 predicts poor prognosis.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism* ; 5'-Nucleotidase/metabolism* ; Antigens, CD19/metabolism* ; Retrospective Studies ; Male ; Female ; Prognosis ; Middle Aged ; Aged ; Adult ; GPI-Linked Proteins

OBJECTIVE: To investigate the effects of wheat-grain moxibustion at the Guanyuan point on testosterone (T) synthesis and the hypothalamic-pituitary-gonadal (HPG) axis in naturally aged mice. METHODS: We fed 40 twelve-month-old SPF male C57BL/6J mice with a normal diet for 3 months, randomized them into a moxibustion and an aged group of an equal number, and selected 7 four-month-old ones as young controls. We treated the animals of the moxibustion group by wheat-grain moxibustion at the Guanyuan point, once 5 moxibustion sticks, qd, 5 times a week, and fed those of the aged group normally, all for 12 weeks. After treatment, we obtained the testicular index of the mice, observed the histomorphology of the testis tissue by HE staining, measured the contents of T in the testis, gonadotropin-releasing hormone (GnRH) in the hypothalamus and total T (tT), free T (fT), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the serum by ELISA, and determined the expressions of silence information regulator-1 (SIRT1), P53, glutathione peroxidase (GPX4) and cholesterol side-chain?cleavage enzyme (CYP11A1) in the testis by Western blot. RESULTS: Compared with the young controls, the mice in the aged group showed obviously losing and dull hair, energy declination, loose structure of the spermatogenic tubule with different degrees of cell loss and rupture, reduced testicular index, and evident aging phenotype. In comparison with the aged mice, the animals of the moxibustion group were fairly energetic and exhibited distinct structure of the spermatogenic tubules, orderly arranged and highly differentiated cells at all levels, significantly increased T level, up-regulated expressions of SIRT1, GPX4 and CYP11A1, and down-regulated expression of P53 in testis tissue, and elevated levels of GnRH, FSH, LH, tT and fT in the HPG axis. CONCLUSION Wheat-grain moxibustion at the Guanyuan point protects testosterone synthesis in the testis tissue of naturally aged mice, promotes negative feedback regulation of the HPG axis, and improves low testosterone.
Animals ; Male ; Moxibustion ; Mice ; Testosterone/metabolism* ; Mice, Inbred C57BL ; Testis/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Triticum ; Gonadotropin-Releasing Hormone/metabolism* ; Luteinizing Hormone/blood* ; Follicle Stimulating Hormone/blood* ; Aging ; Hypothalamus/metabolism* ; Acupuncture Points ; Sirtuin 1/metabolism* ; Hypothalamic-Pituitary-Gonadal Axis

OBJECTIVE: To investigate the action mechanism of formononetin (FN) in regulating T helper type 1 (Th1) cell differentiation and macrophage polarization through JAK/STAT signaling pathways in a mouse model of experimental autoimmune prostatitis (EAP). METHODS: Forty non-obese diabetic (NOD) male mice were randomly divided into four groups: normal control, EAP model control, low-dose FN (LFN, 50 mg/kg) and high-dose FN (HFN, 100 mg/kg). The EAP model was established in the latter three groups by subcutaneous injection of prostate antigens (PAgs) combined with complete Freund's adjuvant (CFA). After modeling, the mice in the LFN and HFN groups were treated intragastrically with FN at 50 and 100 mg/kg/d, respectively, and those in the normal and model controls groups with carboxymethylcellulose sodium (CMC-Na). At 42 days after treatment, all the animals were killed and relevant tissues collected for observation of the pathological changes in the prostate tissue by HE staining, detection of Th1 cell differentiation and macrophage polarization in the prostate by immunofluorescence double staining (labeling CD4 and interferon-γ ［IFN-γ］, inducible nitric oxide synthase ［iNOS］ and CD206), measurement of the ratio of Th1 cells/macrophages in the spleen by flow cytometry and the levels of IFN-γ and tumor necrosis factor-α (TNF-α) in the serum by ELISA, and determination of the expressions of phosphorylated (p)-Janus kinase (JAK)1, JAK1, p-JAK2, JAK2, p-signal transducer and activator of transcription (STAT1) in the prostate tissue by Western blot. RESULTS: Compared with the model controls, the mice treated with low- and high-dose FN exhibited more orderly arrangement of glandular epithelial cells, significantly reduced prostatic tissue inflammation scores (P<0.05), and decreased proportion of Th1 cells and expression of M1 macrophages (P<0.05), but increased expression of M2 macrophages in the prostate and spleen tissues (P<0.05). Besides, the levels of inflammatory cytokines IFN-γ (P<0.05) and TNF-α (P<0.05) in the serum of the mice in the LFN and HFN groups were remarkably reduced, and so were the ratios of p-JAK1/JAK1, p-JAK2/JAK2 and p-STAT1/STAT1 in the prostate tissues at the molecular level (P<0.05), indicating the therapeutic effect of FN on EAP by regulating JAK/STAT signaling pathways, promoting inflammation resolution, and restoring immune balance. CONCLUSION FN alleviates EAP by inhibiting JAK/STAT signaling pathways and regulating Th1 cell differentiation and macrophage polarization.
Animals ; Male ; Prostatitis/metabolism* ; Signal Transduction ; Mice ; Isoflavones/therapeutic use* ; Mice, Inbred NOD ; Autoimmune Diseases/metabolism* ; Macrophages ; Inflammation ; Th1 Cells ; Janus Kinases/metabolism* ; Cell Differentiation ; Disease Models, Animal ; STAT Transcription Factors/metabolism*

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged