Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R2=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.

Objective To explore the effects of Magu Xujin capsule on hip fracture healing and stromal cell-derived factor-1/CXC chemokine receptor 4(SDF-1/CXCR4)signaling pathway in elderly hip fracture rats.Methods The hip fracture model of aged rats was established,and successfully modeled rats were randomly separated into the model group,the low-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule+pathway inhibitor group(the high-dose Magu Xujin capsule and AMD3100 group),with 12 rats in each group.An additional 12 healthy rats were selected as the control group.X-ray was used to observe the healing of hip fractures in rats,and Garrett score was performed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of inflammatory factors related to fracture healing,such as tumor necrosis factor-alpha(TNF-α)and interleukin-10(IL-10).CT scanning analysis was used to determine bone volume fraction(BV/TV)and bone surface area/volume ratio(BS/BV).Immunohistochemistry was applied to detect the expression of fracture healing factor insulin-like growth factor-1(IGF-1)and bone morphogenetic protein-2(BMP-2).Western blot assay was applied to detect the expression of SDF-1/CXCR4 signaling pathway related proteins.Results Garrett score,IL-10 level,BV/TV,BS/BV,the IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the model group than those in the control group,while TNF-α level was higher(P＜0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were higher in the low-dose and high-dose Magu Xujin capsule groups than those in the model group,while TNF-α level was lower(P＜0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the high-dose Magu Xujin capsule+AMD3100 group than those in the high-dose Magu Xujin capsule group,while TNF-α level was higher(P＜0.05).Conclusion Magu Xujin capsule can promote hip fracture healing in aged rats,and its mechanism may be related to the activation of SDF-1/CXCR4 signaling pathway.

Objective To explore the effects of Magu Xujin capsule on hip fracture healing and stromal cell-derived factor-1/CXC chemokine receptor 4(SDF-1/CXCR4)signaling pathway in elderly hip fracture rats.Methods The hip fracture model of aged rats was established,and successfully modeled rats were randomly separated into the model group,the low-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule+pathway inhibitor group(the high-dose Magu Xujin capsule and AMD3100 group),with 12 rats in each group.An additional 12 healthy rats were selected as the control group.X-ray was used to observe the healing of hip fractures in rats,and Garrett score was performed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of inflammatory factors related to fracture healing,such as tumor necrosis factor-alpha(TNF-α)and interleukin-10(IL-10).CT scanning analysis was used to determine bone volume fraction(BV/TV)and bone surface area/volume ratio(BS/BV).Immunohistochemistry was applied to detect the expression of fracture healing factor insulin-like growth factor-1(IGF-1)and bone morphogenetic protein-2(BMP-2).Western blot assay was applied to detect the expression of SDF-1/CXCR4 signaling pathway related proteins.Results Garrett score,IL-10 level,BV/TV,BS/BV,the IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the model group than those in the control group,while TNF-α level was higher(P＜0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were higher in the low-dose and high-dose Magu Xujin capsule groups than those in the model group,while TNF-α level was lower(P＜0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the high-dose Magu Xujin capsule+AMD3100 group than those in the high-dose Magu Xujin capsule group,while TNF-α level was higher(P＜0.05).Conclusion Magu Xujin capsule can promote hip fracture healing in aged rats,and its mechanism may be related to the activation of SDF-1/CXCR4 signaling pathway.

Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.

Local anesthetics are a class of medications that can reversibly block the occurrence and transmission of sensory nerve impulses in the local administration area, which are widely used in clinic for skin and mucous membrane anesthesia, peripheral nerve block anesthesia, spinal nerve anesthesia, and the treatment of chronic pain. The adverse reactions of local anesthetics mainly include allergic reactions, cardiotoxicity, and neurotoxicity. The new dosage forms of local anesthetics include cutaneous administration and sustained-release formulations. The advantage of cutaneous administration is to achieve surface local anesthesia, avoid liver first pass effect, reduce local damage and stimulation caused by injection anesthesia, and improve patient tolerance. The sustained-release dosage form can help maintain a longer lasting anesthetic effect, avoid excessive blood drug concentration caused by rapid absorption of local anesthetic drugs, and thus reduce adverse drug reactions.

Local anesthetics are a class of medications that can reversibly block the occurrence and transmission of sensory nerve impulses in the local administration area, which are widely used in clinic for skin and mucous membrane anesthesia, peripheral nerve block anesthesia, spinal nerve anesthesia, and the treatment of chronic pain. The adverse reactions of local anesthetics mainly include allergic reactions, cardiotoxicity, and neurotoxicity. The new dosage forms of local anesthetics include cutaneous administration and sustained-release formulations. The advantage of cutaneous administration is to achieve surface local anesthesia, avoid liver first pass effect, reduce local damage and stimulation caused by injection anesthesia, and improve patient tolerance. The sustained-release dosage form can help maintain a longer lasting anesthetic effect, avoid excessive blood drug concentration caused by rapid absorption of local anesthetic drugs, and thus reduce adverse drug reactions.

With the rapid development of modern economy, road traffic has become increasingly busy, and the accompanying environmental pollution problem is becoming increasingly prominent. Air pollutants emitted from automobile exhaust, including particulate matters, NO_x, CO, and hydrocarbons (PAHs), can cause high risk of cardiovascular disease and premature death. This article summarizes the related epidemiological research progress on this topic from published literatures in recent years. We reviewed acute and chronic health damage to the cardiovascular system caused by traffic related air pollutants, including changes in heart rate variability and blood system indicators, potential association with coronary arteriosclerosis, coronary heart disease, and death of cardiovascular disease. The results show that traffic-related air pollutants can cause decrease in heart rate variability, increased blood pressure and changes in blood indicators, increase acute mortality from cardiovascular diseases. Long-term exposure to traffic-related air pollutants can induce increased risk of coronary atherosclerosis and coronary heart disease, and lead to increased mortality from cardiovascular diseases. In the future, more attention should be paid to traffic-related air pollution, and more researches are recommended to comprehensively evaluate the relationship between traffic-related air pollution and cardiovascular health damages, especially in early-stage. At the same time, active researches on the mechanism of cardiovascular toxicity of traffic-related air pollutants are needed, so as to promote the early prevention of cardiovascular diseases.

Objective: To evaluate the effects of sevoflurane on microglial polarization after traumatic brain injury (TBI) in rats. Methods: Seventy-two healthy adult male Sprague-Dawley rats, weighing 230-250 g, were divided into 3 groups (n=24 each) using a random number table method: sham operation group (group Sham), group TBI, and TBI plus sevoflurane anesthesia group (group TBI+ Sevo). TBI models were established by using Feeney′s method in TBI and TBI+ Sevo groups, 30 min later 2.4% sevoflurane was inhaled for 1 h once a day for 3 consecutive days in TBI+ Sevo group, while pure oxygen was inhaled instead in Sham and TBI groups.At 1, 3, 7 and 14 days after establishing the model, 6 rats were selected, the neurological function was evaluated with the modified neurologic severity score (mNSS), and tail venous blood samples were taken for determination of tumor necrosis factor-a (TNF-α), interleukin-1beta (IL-1β) and IL-6 concentrations by enzyme-linked immunosorbent assay.The rats were then sacrificed, the limbic cortical tissues of brain contusion lesion were taken for determination of cell apoptosis (by TUNEL) and expression of microglial marker Iba-1, microglial M1 phenotypic marker CD86 and microglial M2 phenotypic marker CD206 (by Western blot). Results: Compared with group Sham, the mNSS score, apoptosis rate of cortical cells, expression of Iba-1, CD86 and CD206, and concentrations of serum TNF-α, IL-1β and IL-6 were significantly increased in TBI and TBI+ Sevo groups (P<0.05). Compared with TBI group, the mNSS score, apoptosis rate of cortical cells, expression of Iba-1 and CD86 and concentrations of serum TNF-α, IL-1β and IL-6 were significantly decreased, and the expression of CD206 was up-regulated in TBI+ Sevo group (P<0.05). Conclusion The mechanism by which sevoflurane anesthesia reduces TBI may be related to promoting microglial polarization and inhibiting systemic inflammatory response in rats.

Tumor radiotherapy is established on the basis of clinical oncology, radio-physics and radiobiology, and has become one of the three major therapeutic methods for malignant tumors. With the pace of socialist construction in China, the subject of radiotherapy in Shanxi province has developed from scratch and from small to large for more than 60 years. Remarkable achievements have been made in the establishment of departments, the updating of technical equipment, the increase of employees and clinical scientific research. This article reviews and summarizes the development history of tumor radiotherapy in Shanxi province.