OBJECTIVES: To investigate the protective effect and underlying mechanism of Chinese herb medicine Gandou Bushen decoction (GBD) on ovarian injury in murine hepatolenticular degeneration (HLD) model. METHODS: The chemical constituents of GBD were analyzed using liquid chromatography-mass spectrometry (LC-MS). Forty female C3He-Atp7b^tx-J mice (6-week-old) were randomly divided into model, penicillamine (positive control), low-dose GBD, and high-dose GBD groups. Ten DL syngeneic female mice served as the normal control group. Body and ovarian weights were measured to calculate the ovarian coefficient. Ovarian copper content was detected by complexometric colorimetry. Histopathological and ultrastructural changes were observed by hematoxylin-eosin staining and transmission electron microscopy, respectively. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone were measured by enzyme-linked immunosorbent assay (ELISA). RNA sequencing was performed to identify differentially expressed genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A copper overload cell model was established in ovarian granulosa cells(iCell-0114a)by inducing them with copper sulfate. Cells were divided into normal control, model control, and low-, medium-, and high-dose GBD groups. The mRNA expression of FSH receptor (FSHR), steroidogenic acute regulatory protein (StAR), insulin-like growth factor-1 (IGF-1), receptor for advanced glycation end products (RAGE), and nuclear factor κB (NF-κB) was detected by quantitative reverse transcription polymerase chain reaction. The levels of TNF-α, IL-1β, and IL-6 were measured by ELISA. Superoxide dismutase (SOD) activity was measured using a WST-1 assay. Reactive oxygen species (ROS) levels were measured using DCFH-DA fluorescence, and mitochondrial membrane potential was assessed using JC-1 staining coupled with flow cytometry. Protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, advanced glycation end products (AGE), RAGE, and NF-κB was determined by Western blotting. RESULTS: A total of 1465 chemical components were identified in GBD. Compared with the normal control group, the model group showed decreased body weight, ovarian weight, and ovarian coefficient (all P<0.01). GBD treatment alleviated tissue copper deposition (P<0.01), improved ovarian histomorphology and ultrastructure, and increased serum levels of FSH, LH, estradiol, and progesterone (all P<0.01). RNA sequencing identified 507 differentially expressed genes. KEGG enrichment analysis indicated that the mechanism underlying GBD's protective effects primarily involved the AGE/RAGE/NF-κB signaling pathway. In copper-overloaded granulosa cells, GBD dose-dependently increased the mRNA expression of FSHR, StAR, and IGF-1, reduced the levels of TNF-α, IL-1β, and IL-6, increased SOD activity, and decreased ROS levels (all P<0.01). The medium- and high-dose GBD groups showed a lower percentage of cells with mitochondrial depolarization (both P<0.01). All GBD dose groups showed decreased expression of Bax and caspase-3 (all P<0.05), while the medium- and high-dose groups showed increased Bcl-2 expression. Furthermore, medium and high doses of GBD reduced the protein expression of AGE, RAGE, and NF-κB, and all doses downregulated the mRNA expression of RAGE and NF-κB (P<0.05 or P<0.01). CONCLUSIONS GBD ameliorates ovarian injury in HLD, and its mechanism of action is associated with the suppression of the AGE/RAGE/NF-κB signaling pathway.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans ; Aminolevulinic Acid/therapeutic use* ; Skin Neoplasms/pathology* ; Photochemotherapy/methods* ; Female ; Carcinoma, Squamous Cell/pathology* ; Middle Aged ; Photosensitizing Agents/therapeutic use* ; Carcinoma, Basal Cell/drug therapy*

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To investigate the clinical significance of combined cerebrospinal fluid(CSF)and routine blood parameter analysis in differentiating between multiple cerebral glioma(MCG)and primary central nervous system lymphoma(PCNSL).Methods We Rretrospectively analyzed the clinical data,CSF and routine blood indicators levels of 62 MCG patients and 56 PCNSL patients admitted to Beijing Tiantan Hospital,Capital Medical University from November 2017 to March 2023.Additionally,we assessed the diagnostic value of individual meaningful indicators as well as their combinations in distinguishing between MCG and PCNSL.Results The levels of CSF total cell count,CSF white cell count,CSF:pro,lactate,routine bloodperipheral neutrophil count,and neu-trophil percentage were significantly higher in the MCG group than in the PCNSL group(P<0.05);while the levels of CSF:Glu,CSF:cl,routine blood lymphocyte count,eosinophil,lymphocyte percentage,and eosinophil percent-age were significantly higher in the PCNSL group than in the MCG group(P<0.05).The AUCs of CSF cell count,CSF white cell count,CSF:pro,lactate,routine blood neutrophil count,neutrophil percentage for differentiating MCG from PCNSL were 0.900,0.899,0.797,0.867,0.828 and 0.772 respectively;sensitivities were 72.4%,77.6%,63.8%,67.2%,72.4%,82.8%,77.6%and 81%,with sensitivities of 97.1%,100%,88.2%,91.2%,88.2%,64.7%,100%and 94.1%,respectively.In addition,the combined detection of CSF total cell count,CSF white cell count,CSF:pro,routine blood neutrophil count and neutrophil percentage in CSF had an AUC of 0.919 for differentiating MCG from PCNSL,with a sensitivity and specificity of 77.6%and 100%,respectively.Conclusions Combined detection of CSF indicators including CSF total cell count,CSF white cell count,CSF:pro,along with routine blood markers such as neutrophil count and neutrophil percentage,holds significant clinical utility for differ-entiating between MCG and PCNSL.

Objective:To study the prevalence and association factors of depressive and anxiety disorders in the hypertensive population.Methods:Using the database obtained from the 2013 China Chronic Disease and Risk Factor Surveillance and the 2013-2015 China Mental Health Survey,4 861 hypertensive residents were used as study subjects.And using the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)as diagnostic criterion for depressive and anxiety disorders,the 12-month prevalence was calculated.Multifactorial lo-gistic regression models were used to explore the association factors of hypertension comorbid depressive and anxie-ty disorders.Results:The 12-month prevalence rates of depressive disorders and anxiety disorders were 4.1％and 5.0％in 4 861 hypertensive residents.Chinese Han[OR(95％CI):2.00(1.01-3.93)],lack of sleep[OR(95％CI):1.82(1.34-2.48)],having myocardial infarction[OR(95％CI):2.35(1.18～4.67)]and stroke in the past year[OR(95％CI):2.10(1.19-3.72)],and chronic obstructive pulmonary disease[OR(95％CI):2.11(1.11-4.05)]were risk factors of hypertension comorbid depressive disorder.Hypertensive people with controlled blood pressure[OR(95％CI):2.01(1.30-3.13)]had a higher risk of co-morbid depressive disorder than those with blood pressure above the normal range on this measurement.Chinese Han[OR(95％CI):2.51(1.32-4.80)],Southwest China[OR(95％CI):1.64(1.02-2.63)],and lack of sleep[OR(95％CI):1.45(1.09-1.93)]were risk factors of hypertension comorbid anxiety disorder.Former but current non-smoking[OR(95％CI):0.48(0.23-0.99)]was a protective factor of hypertension comorbid anxiety disorder.Conclusion:The 12-month prevalence of anxiety disorder was higher than that of depressive disorder in this hypertensive population.Both Han and sleep deprived hypertensive people had a higher risk of comorbid depressive and anxiety disorders.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.