ObjectiveTo explore the therapeutic effects and mechanisms of modified Danggui Shaoyaosan on acne based on the c-Jun N-terminal kinase （JNK）/p38 mitogen-activated protein kinase （p38 MAPK） pathway. MethodsA rat ear acne model was established in SD rats， and the rats were divided into a blank group， a model group， and low-， medium-， and high-dose groups of modified Danggui Shaoyaosan （7.15， 14.30， 28.60 g·kg·d^-1）， with six rats in each group. After the administration for 14 consecutive days， morphological changes in the rats' auricles were observed， and hematoxylin-eosin （HE） staining was used to examine the pathological changes in the acne-affected ear tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the ear tissue. Quantitative reverse transcription polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression levels of Caspase-3， B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， JNK， and p38 MAPK in the ear tissue. Additionally， Western blot analysis was conducted to assess the protein levels of Caspase-3， Bcl-2， Bax， JNK， and p38 MAPK in the ear tissue. The active components and key targets of modified Danggui Shaoyaosan in the treatment of acne were identified through network pharmacology analysis. Molecular docking was then employed to evaluate the interactions between the main active components and the key targets. ResultsThe results of the animal experiment demonstrated that compared with those in the blank group， rats in the model group exhibited redness， swelling， thickening， hardening， dryness， and roughness of the auricle. The surface showed sebaceous scales and desquamation， accompanied by acne-like lesions such as papule-like elevations or cysts. Histopathological changes included keratinization， epidermal thickening， dermal collagen fiber degeneration and necrosis， subcutaneous muscle degeneration and necrosis， inflammatory cell infiltration， and fibrous tissue proliferation. The mRNA and protein expression levels of IL-1β， TNF-α， Caspase-3， Bax， JNK， and p38 MAPK were significantly increased （P<0.01）， while those of Bcl-2 were significantly decreased （P<0.01）. In comparison to the model group， the modified Danggui Shaoyaosan groups showed marked improvement in acne-like lesions of the auricle， with varying degrees of histopathological damage reduction. Additionally， the mRNA and protein expression levels of IL-1β， TNF-α， Caspase-3， Bax， JNK， and p38 MAPK in the tissue were significantly decreased （P<0.05， P<0.01）， while those of Bcl-2 were significantly increased （P<0.05， P<0.01）. Network pharmacology analysis indicated that the key compounds in modified Danggui Shaoyaosan responsible for its effects in treating acne may include acacetin， kaempferol， luteolin， quercetin， wogonin， and baicalein. These compounds exerted their effects by modulating core targets such as TNF， IL-1β， Caspase-3， and Bcl-2， thereby alleviating inflammation and apoptosis and ultimately improving acne symptoms. ConclusionModified Danggui Shaoyaosan may exert its therapeutic effects on acne by inhibiting the activation of the JNK/p38 MAPK pathway， thereby alleviating inflammation and apoptosis.

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120-/-)and THP-1 cells. Method Six-eight-week-old C6orf120-/-and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors. Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68+CD86+M1 macrophages from the liver and spleen in the C6orf120-/-rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68+CD80+M1 macrophages and inhibited the CD68+CD206+M2 phenotype. Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120-/-rats.

Objective:To explore the role of interleukin-18 (IL-18) in the pathogenesis of dermatomyositis (DM) associated with positive anti-melanoma differentiation-associated gene 5 antibodies(MDA5-DM).Methods:Twenty-eight cases of MDA5-DM in the department of rheumatology and immunology, the first hospital of Nanjing medical university and the first affiliated hospital od Wannan medical colledge from August 2018 to December 2011 were included in this study, comprising 15 cases with combined rapidly progressive interstitial pneumonia (RPILD) and 13 cases without RPILD (nonRPILD). Additionally, 28 cases of antisynthetase syndrome (ASS) and 28 healthy volunteers (HC) were included for comparison. Clinical, laboratory, and imaging data were collected for both the DM and ASS groups. Serum IL-18 levels were measured using ELISA. Independent t test, Mann-whitney U test, χ2 test and Fisher′s exact probability method were used for analysis. Results:Significant differences were observed in LDH, hydroxybutyrate dehydrogenase (HBDH), ESR, CRP, serum ferritin (SFE), and IL-18 levels between the MDA5-DM group, the ASS group and the HC group ( F=46.65, 43.19, 31.28, 23.94, 30.94, 49.44, all P<0.001). Additionally, lymphocyte counts and hemoglobin levels differed significantly among the three groups( F=35.26, P<0.001; F=18.59, P<0.001). MDA5-DM patients exhibited higher incidences of Gottron′s sign, helitrope rash, periungual erythema, skin ulcers, and RPILD compared to ASS patients ( χ2=20.96, P<0.001; χ2=5.85, P=0.016; χ2=13.69, P<0.001; χ2=9.16, P=0.002; χ2=4.79, P=0.029). However, the incidence of mechanic′s hand was lower in MDA5-DM patients ( χ2=3.90, P=0.048). The level of IL-18 significantly decreased in MDA5-DM after treatment[(104.28(71.96,151.10)pg/ml vs. 78.30(56.20, 94.80)pg/ml, =2.27, P=0.023)]. Similar reductions were observed in the ASS group[(72.30(61.39, 95.94)pg/ml vs. 45.30(29.00,84.10)pg/ml, Z=2.691, P=0.007]. The IL-18 level changes in the MDA5-DM combined with RPILD group were not statistically significant [99.49 (77.65, 130.87)pg/ml vs. 89.40(54.80, 120.20)pg/ml, Z=0.65, P=0.515]. In the MDA5-DM survival group, IL-18 levels decreased significantly after treatment [59.45(53.58, 81.63)pg/ml vs. 106.37(83.62, 152.07)pg/ml, Z=2.80, P=0.005], while the changes in the IL-18 levels of patients in the MDA5-DM death group were not statistically significant [99.49(56.70, 140.15)pg/ml vs. 94.80(71.40, 155.45)pg/ml, Z=1.75, P=0.080]. Conclusion:MDA5-DM patients are different from the ASS patients in clinical manifestations and indicators involved in laboratory tests. The expression level of IL-18 tends to increase during the active phase of MDA5-DM and ASS, and decrease with remission of the disease. MDA5-DM may play an important role in the pathogenesis, and persistent high level of IL-18 is responsible for RPILD and death of MDA5-DM. Sustained high level of IL-18 can be used as a potential biomarker for the estimating development of MDA5-DM into RPILD.

Objective:To observe the development process of the neuronal synapse in cerebral cortex and basal ganglionic eminence(GE)regions of the mice,and to clarify the differences in the development of excitatory and inhibitory synapses in different brain regions in vivo and in vitro.Methods:The female C57BL/6 mice were euthanized by cervical dislocation from the 13.5th day to the 15.5th day during the pregnancy,and the embryos were collected under the sterile conditions.The cortex and GE regions of brain tissue of the embryonic mice were gradually isolated under microscope.The primary neurons from the embryonic mice were cultured in vitro,and the cell samples were collected on the 3rd,7th,14th,and 21th days,respectively,and regarded as culture 3 d,7 d,14 d,and 21 d groups.The expression levels of postsynaptic density 95(PSD95)and Gephyrin mRNA in the primary neurons from the cortex and GE regions of the mice in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Immunofluorescence method was used to detect the expression levels of vesicular glutamate transporter 1(vGLUT1),PSD95,vesicular GABA transporter(vGAT),and Gephyrin proteins in the neurons from the cortex and GE regions of the mice in various groups.Immunofluorescence method was also used to detect the expression levels of vGLUT1 and vGAT proteins in the neurons from the cortical and GE regions in brain tissue of the embryonic mice.Results:Compared with culture 3 d group,the expression levels of PSD95 and Gephyrin mRNA in cortex and GE regions of the mice in culture 14 d and 21 d groups were significantly increased(P<0.01).Compared with cortex area,the expression level of Gephyrin mRNA in the neurons from GE region of the mice in culture 14 d group was significantly decreased(P<0.01).The microscope observation results showed that the excitatory and inhibitory synapses in the neurons from cortex and GE regions of the mice in culture 14 d group showed preliminary development,with positive expression of relevant proteins;among them,the excitatory synaptic proteins showed more distinct positive expression in the cortex neurons,and the presynaptic vGLUT1 and postsynaptic PSD95 molecules exhibited co-localization in the cell bodies and protrusions of the cortical neurons;the inhibitory presynaptic vGAT protein and postsynaptic Gephyrin protein in the neurons from GE region also exhibited co-localization in the cell bodies and protrusions,and there were more distinct expressions of the presynaptic molecule proteins than postsynaptic molecule proteins.Compared with cortex region,the levels of vGLUT1 and PSD95 proteins in the neurons from GE region of the mice in culture 14 d group were significantly decreased(P<0.01),while the levels of vGAT and gephyrin proteins were significantly increased(P<0.01).In culture 21 d group,the positive expressions of synaptic protein in the neurons from cortex and GE regions were increased,and the excitatory and inhibitory synapses further matured and enhanced.In the neurons from cortex and GE regions,rich patterns of corresponding pre-and postsynaptic expression were formed in the cell bodies and protrusions,and synapse structures showed gradual,positive development,with more apparent expression of presynaptic molecules compared wih postsynaptic proteins.Compared with cortex region,the levels of vGLUT1 and PSD95 proteins in the neurons from GE region of the mice in culture 21 d group were significantly decreased(P<0.01),and the levels of vGAT and Gephyrin proteins were significantly increased(P<0.01).Compared with cortex region,the expression level of vGLUT1 protein in the neurons from GE region in brain tissue of the embryonic mice was significantly decreased(P<0.01),while the expression level of vGAT protein was significantly increased(P<0.05).Conclusion:There are distinct differences in synaptic development between the neurons from cortex and GE regions,the excitatory synapses develope earlier in the cortical region and the inhibitory synapses develope earlier in the GE region.The region-specific development of synapses suggests that different types of neural diseases with different cell types might originate from different developmental processes.

OBJECTIVE: To investigate the effectiveness of three-dimensional (3D)-printed hemi-pelvic prosthesis for revision of aseptic loosening or screw fracture of modular hemi-pelvic prosthesis. METHODS: Between February 2017 and January 2020, 11 patients with aseptic loosening or screw fracture of modular hemi-pelvic prosthesis were revised using 3D-printed hemi-pelvic prostheses. There were 7 males and 4 females with an average age of 44 years (range, 25-60 years). In the first operation, all patients underwent total tumor resection, modular hemi-pelvic prosthesis reconstruction, and autologous femoral head transplantation. According to the Enneking pelvic partition system, 8 cases were resected in zones Ⅰ+Ⅱ and 3 cases in zones Ⅰ+Ⅱ+Ⅲ. The interval from the initial operation to this revision ranged from 14.3-66.2 months, with an average of 35.8 months. The operation time, the amount of intraoperative bleeding, and the occurrence of complications were recorded. At 6 months after the first operation, before revision, and at last follow-up, the American Musculoskeletal Tumor Society (MSTS) score and Harris score were used to evaluate the recovery of lower limb function. The pain-free walking distance of patients without brace assistance was recorded at last follow-up. X-ray films were taken at 1 month after the first operation, before revision, and at 1 month after revision, the acetabulum position was assessed by the differences in weight arm and cup height between bilateral hip joints. At last follow-up, the digital X-ray tomography was taken to evaluate the prosthesis-bone integration and the occurrence of aseptic loosening. RESULTS: The operation time was 182.6-238.0 minutes (mean, 197.4 minutes). The amount of intraoperative bleeding was 400-860 mL (mean, 550.0 mL). All incisions healed by first intention with no infection, hip dislocation, nerve damage, or vascular-related adverse events. The MSTS score and Harris score at last follow-up were significantly higher than those at 6 months after the first operation and before revision ( P<0.05), while the score before revision was significantly lower than that at 6 months after the first operation ( P<0.05). At last follow-up, the patients were able to walk more than 1 000 meters painlessly without brace assistance. Imaging review showed that the difference of cup height at 1 month after revision was significantly lower than that at 1 month after the first operation and before revision, and at 1 month after the first operation than before revision operation, and the differences were significant ( P<0.05). There was no significant difference in the difference of weight arm among three time points ( P>0.05). All prostheses were well integrated, and no aseptic loosening of the prosthesis or screw fracture occurred. CONCLUSION Revision with 3D-printed hemi-pelvic prostheses benefited in reconstructing stable pelvic ring and natural bodyweight transmission for patients encountering the aseptic loosening or screw fracture of modular hemi-pelvic prosthesis. Early postoperative rehabilitation training can maximize the recovery of patient limb function, reduce pain during walking, and reduce the incidence of complications.
Male ; Female ; Humans ; Adult ; Arthroplasty, Replacement, Hip/methods* ; Hip Prosthesis ; Treatment Outcome ; Prosthesis Failure ; Fractures, Bone/surgery* ; Retrospective Studies ; Neoplasms

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

Benzodiazepines are among the most commonly used drugs in the field of anesthesia. Remazolam is a newly developed ultra-short-acting benzodiazepine, which has the characteristics of rapid onset, rapid recovery, high safety, and less side effects such as hypotension and respiratory depression. The aim of this review is to summarize the progress of pharmacokinetics, clinical pharmacology mechanism of action and clinical application of remazolam.

Objective To evaluate the current situation of radioactive contamination in the soil around a decommissioned uranium mine by combined determination of ²¹⁰Pb and ²¹⁰Po activity concentrations. Methods Soil samples were collected around a decommissioned uranium mine. ²¹⁰Po and the ²¹⁰Pb decay product ²¹⁰Bi were plated on a copper sheet by self-deposition at a constant temperature. Gross α and gross β counts were measured using a low-background α/β counter. The activity concentrations of ²¹⁰Pb and ²¹⁰Po in soil were calculated. The radioactive contamination was evaluated using geological accumulation index. Results The activity concentrations of ²¹⁰Pb and ²¹⁰Po in the soil around the decommissioned uranium mine were 873.7-2315.5 and 956.0-2315 Bq·kg⁻¹, respectively. The activity concentrations of ²¹⁰Pb and ²¹⁰Po in nearby farmland soil were 54.2-257.8 and 59.1-234.5 Bq·kg⁻¹, respectively. Evaluation with the geological accumulation index showed that the level of nearby farmland contamination was 0-2, indicating zero to moderate radioactive contamination of the farmland. Conclusion The relatively high radioactivity around the decommissioned uranium mine requires attention to the transfer, diffusion, and ingestion of the uranium decay products ²¹⁰Pb and ²¹⁰Po in the surrounding soil to avoid radioactive contamination of the environment.

Clinical data of 210 patients with early colorectal cancer and precancerous lesion treated by endoscopic submucosal dissection (ESD) in the Digestive Endoscopy Center of the Seventh Medical Center of Chinese PLA General Hospital from January 2015 to March 2018 were collected and analyzed retrospectively. Patients were divided into two groups according to the age: the elderly group (≥65 years old, 100 cases) and the non-elderly group (<65 years old, 110 cases). The en bloc resection rate, complete resection rate,and curative resection rate of the elderly group were 92.0% (92/100), 91.0% (91/100) and 89.0% (89/100), respectively. The above indicators of the non-elderly group were 90.9% (100/110) ( P=0.972), 90.0% (99/110) ( P=0.991) and 88.2% (97/110) ( P=1.000), respectively. The incidence of intraoperative perforation in the elderly group was 4.0% (4/100) and in the non-elderly group was 6.4% (7/110) ( P=0.543). Delayed postoperative bleeding rate was 2.0% (2/100) in the elderly group, and 0 (0/110) in the non-elderly group ( P=0.226). ESD is effective and safe in treating early colorectal cancer and precancerous lesion in elderly patients.