OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

BACKGROUND:At present,research has only shown that the cervical lordosis ratio can be an important factor in predicting the loss of lordosis curvature after laminoplasty,and no one has studied whether the cervical lordosis ratio,a dynamic level indicator,can be one of the decision-making factors for the selection of posterior cervical surgical procedures. OBJECTIVE:To investigate whether the cervical lordosis ratio,an index of cervical hyperextension and hyperflexion,can be used as a selective index for laminoplasty and laminectomy fusion. METHODS:A retrospective review of 141 patients who had undergone posterior cervical surgery more than one year of follow-up due to multi-level cervical spondylotic myelopathy from December 2015 to March 2020 was performed.Among them,63 patients received laminectomy and fusion(laminectomy and fusion group)and 78 patients received laminoplasty(laminoplasty group).The demographic statistics(gender,age,body mass index,follow-up time),imaging indexes such as C2-7 Cobb angle,C2-7 range of motion,flexion Cobb angle,extension Cobb angle,flexion range of motion and extension range of motion,clinical effect indexes such as Japanese Orthopaedic Association score and visual analog scale score were compared between the two groups.The evaluation index of cervical lordosis alignment change was C2-7 Cobb angle difference before and after operation(ΔCL).Cervical lordosis ratio was equal to 100%×flexion range of motion/C2-7 range of motion.Receiver operating characteristic curve analysis was used to determine the role of cervical lordosis ratio in predicting postoperative severe cervical lordosis loss(ΔCL≤-10°).According to the critical value of cervical lordosis ratio(68.5%),all patients were divided into low cervical lordosis ratio group and high cervical lordosis ratio group.In these two ratio groups,the cervical lordosis alignment index and clinical effect index between the two operation groups were discussed again. RESULTS AND CONCLUSION:(1)Cervical lordosis alignment decreased after laminectomy and fusion and laminoplasty(P=0.039,P=0.002),and cervical lordosis alignment change in laminoplasty group(ΔCL)was greater than that of laminectomy and fusion group,and the difference between the two groups was statistically significant.(2)Based on receiver operating characteristic curve analysis,cervical lordosis ratio in predicting severe cervical lordosis alignment change(ΔCL≤-10°)had good identification ability(area under the curve=0.792).(3)In low cervical lordosis ratio group,there was no significant difference in cervical lordosis alignment change(ΔCL)between laminectomy and fusion group and laminoplasty group(P=0.141).(4)In high cervical lordosis ratio group,the ΔCL of laminoplasty group was greater than that in laminectomy and fusion group(P=0.001),which had a higher probability of postoperative severe cervical lordosis alignment change(ΔCL≤-10°)(43%,29%).(5)It is indicated that cervical lordosis ratio can be used as a decision-making index for the choice of posterior surgery for multi-level cervical spondylotic myelopathy.Laminoplasty can be considered in the low cervical lordosis ratio group,while laminectomy and fusion can be considered in the high cervical lordosis ratio group.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

The plasma membrane (PM) plays an essential role in maintaining cell homeostasis, therefore, timely and effective repair of damage caused by factors such as mechanical rupture, pore-forming toxins, or pore-forming proteins is crucial for cell survival. PM damage induces membrane rupture and stimulates an immune response. However, damage resulting from regulated cell death processes, including pyroptosis, ferroptosis, and necroptosis, cannot be repaired by simple sealing mechanisms and thus, requires specialized repair machinery. Recent research has identified a PM repair mechanism of regulated cell death-related injury, mediated by the endosomal sorting complexes required for transport (ESCRT) machinery. Here, we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury, with particular focus on processes related to regulated cell death. This overview, along with continued research in this field, may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.

Objective To understand the willingness of general practitioner(GP) to enhance working competence in community healthcare centers in Shanghai and provide a basis for the competence training of GPs in community healthcare centers. Methods In August 2023,GPs were selected from some community healthcare centers in Shanghai and their willingness to enhance working competence were studied by a questionnaire survey.The survey included 39 secondary indicators in three dimensions:general practice theory,skills,and humanity. Results A total of 1 192 GPs completed the questionnaire,with an effective rate of 100%.The total score of GPs' willingness to enhance their working competence was 258.45±80.93,and the mean score of the three dimensions was 6.63±2.08.The score for the general practice theory was the highest (6.92±1.95),while that for general practice humanity was the lowest (6.44±2.34) among the three dimensions.The score of willingness to enhance working efficiency differed across different age ranges (P<0.001),professional titles (P<0.001),years of work (P<0.001),and educational backgrounds of GPs (P=0.039).Those with the age younger than 30 years old,junior professional titles,less than 5 years of work experience,and a college degree or below had the highest willingness score to enhance their working competence.Among the top three secondary indicators of willingness score in each dimension,the top three methods of working competence enhancement were community general practice and specialized healthcare services combined with outpatient learning,flexible further training,and continuing education courses.Conclusions There is an urgent need for young GPs in community healthcare centers in Shanghai to enhance their working competence.Targeted enhancement plans can be provided to different groups of GPs with different characteristics through community general practice and specialized healthcare services combined with outpatient learning,flexible further training,and continuing education courses,which can further enhance the ability and quality of the GP team.
Humans ; China ; General Practitioners/psychology* ; Surveys and Questionnaires ; Community Health Centers ; Clinical Competence ; Female ; Adult ; Male ; Attitude of Health Personnel ; Middle Aged

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

Fracture healing is a complex process that necessitates the synergistic action of various cells and molecules. Macrophages play an indispensable and crucial regulatory role in the process of fracture repair, influencing stages such as inflammatory modulation, angiogenesis, and tissue remodeling. This article delves into the functional characteristics of macrophages and their roles at different stages of fracture healing. Additionally, it explores the impact of aging macrophages on the healing process. Furthermore, the potential of emerging therapies, such as hydrogel-based treatments and exosomes, in modulating macrophage responses is analyzed. This study provides a theoretical foundation for the development of innovative therapies aimed at enhancing the efficacy of fracture healing.

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 trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

Objective To investigate the levels and influencing factors for eye lens dose of interventional radiology workers, and to provide a basis for reasonable and scientific radiation protection. Methods Thermoluminescent eye lens dosimeters were used to monitor the left and right eye lens doses of interventional radiology workers in real time during different surgical positions and varying eye protection conditions. The annual eye lens doses for the operators were estimated based on their yearly workload. The differences in eye lens doses under different conditions were analyzed and the influencing factors were identified. Results For individual interventional operations, the range of personal dose equivalent H_p(3) of the left eye of interventional radiology workers was ( < MDL ~ 418.33) μSv, the median (Q₁, Q₃) was 9.29 ( < MDL, 40.79) μSv, and the mean was 40.79 ± 70.36 μSv. The estimated annual eye lens doses were 4.05 mSv and 17.80 mSv based on the median and mean values of the eye lens dose of a single operation multiplied by average annual frequency of operations per person, respectively. The left eye lens dose was higher than the right eye lens dose of the same operator (Z = −4.24, P < 0.05), and the dose of the right eye lens was strongly positively correlated with that of the left eye lens. The left eye lens dose of the first surgeon was higher than that of the second surgeon in the same operation (Z = −3.10, P < 0.05). The eye lens dose was influenced by operator position (χ² = 9.149, P = 0.002, OR = 8.343), eye protection (χ² = 4.619, P = 0.032, OR = 4.352), and air kerma area product (χ² = 8.032, P = 0.005, OR = 5.488). Conclusion According to the results of this study, a significant portion of interventional operators have eye lens doses that approach or exceed international occupational dose limits. It is recommended to pay attention to the operation frequency of the first operator and the air kerma area product of interventional operation, and strengthen radiation protection and dose monitoring for the eye lens of interventional radiology workers.