This study aims to investigate the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung carcinoma-bearing mice via the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2α(eIF2α)/activated transcription factor 4(ATF4)/C/EBP homologous protein(CHOP) signaling pathway. Sixty SPF-grade male C57BL/6 mice were selected and assigned into a blank group and a modeling group by the random number table method. After modeling of the Lewis lung carcinoma, the mice in the modeling group were randomized into model, cisplatin(5 mg·kg~(-1), once a week), and low-, medium-, and high-dose(1.7, 3.5, and 7.05 g·kg~(-1), respectively, once a day) Guiqi Yiyuan Ointment+cisplatin(5 mg·kg~(-1)) groups(n=10). After 14 days of continuous intervention, the spleen, thymus, and tumor samples of the mice were collected, weighed, and recorded, and the spleen index, thymus index, and tumor suppression rate were calculated. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes in the tumor tissue. The morphological changes of the endoplasmic reticulum of tumor cells were observed by transmission electron microscopy. The positive expression of phosphorylated eIF2α(p-eIF2α) and ATF4 in the tumor tissue was detected by immunofluorescence. Western blot was employed to determine the protein levels of phosphorylated PERK(p-PERK), p-eIF2α, ATF4, CHOP, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinase inhibitor 1A(p21), and cyclinD1 in the tumor tissue. Real-time fluorescent quantitative PCR was employed to determine the mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, Bcl-2, p21, and cyclinD1 in the tumor tissue. Compared with the blank group, the model group showed decreases in spleen index and thymus index(P<0.05). Compared with the model group, the cisplatin group showed decreases in spleen index and thymus index(P<0.05), and the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups presented increases in spleen index and thymus index(P<0.05). In addition, the treatment groups all showed decreased tumor mass(P<0.05), increased tumor cell lysis and nuclear rupture, widened gap between rough endoplasmic reticulum, enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). Compared with the cisplatin group, the combination groups showed increases in spleen index and thymus index(P<0.05) as well as mean optical density(P<0.05), and the high-dose Guiqi Yiyuan Ointment+cisplatin group showed decreased tumor mass(P<0.05). In addition, the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups showcased enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). In conclusion, Guiqi Yiyuan Ointment combined with cisplatin can effectively inhibit the growth of Lewis lung carcinoma in mice by regulating the expression of proteins related to the PERK/eIF2α/ATF4/CHOP signaling pathway and promoting cell cycle arrest and apoptosis.
Animals ; Cisplatin/administration & dosage* ; Activating Transcription Factor 4/genetics* ; Eukaryotic Initiation Factor-2/genetics* ; eIF-2 Kinase/genetics* ; Carcinoma, Lewis Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Mice ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Transcription Factor CHOP/genetics* ; Ointments/administration & dosage* ; Humans ; Cell Proliferation/drug effects* ; Antineoplastic Agents/administration & dosage*

OBJECTIVE: To explore the safety and effectiveness of separation surgery in patients with neurological symptoms of spinal metastases. METHODS: From January 2020 to December 2022, 14 patients with neurological symptoms of spinal metastases underwent separation surgery, including 7 males and 7 females, aged from 30 to 76 years old with an average of (61.57±12.16) years old. In comparison with eleven patients underwent conservative treatment during the same period, including 6 males and 5 femals, aged from 46 to 88 years old with an average of (66.55±12.32) years old. The changes in visual analogue scale (VAS), Frankel grades, Karnofsky scores, and quality of life score (QOL) before and after treatment were compared between two groups. RESULTS: Fourteen patients in the separation surgery group underwent surgery successfully, with surgery time of (218.57±50.00) minutes and intraoperative blood loss of (864.29±332.97) ml, 2 patients developed delayed hematoma and recovered well finally after emergency surgery, the follow-up time was 3 to 36 months, after separation surgery, the pain was significantly relieved, and neurological function recovered well in the patients. Three months after treatment, the VAS in the separation surgery group (1.43±0.76) scores was significantly lower than that in the conservative treatment group (8.64±0.51) scores (P<0.05);and the Frankel grades, Karnofsky scores, and QOL scores in the separation surgery group were significantly better than those in the conservative treatment group(P<0.05). CONCLUSION For patients with obvious neurological symptoms of spinal metastases, separation surgery not only can rapidly relieve nerve compression but also carry relatively low surgical risks, and improve the quality of life of patients.
Humans ; Female ; Male ; Middle Aged ; Aged ; Spinal Neoplasms/complications* ; Adult ; Aged, 80 and over ; Quality of Life

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVE: To investigate whether Buyang Huanwu Decoction (BYHWD) had a good curative effect on the neuroprotection of red nucleus neurons after spinal cord injury (SCI) and the possible molecular mechanism. METHODS: Ninety male Sprague-Dawley rats were divided into 5 groups (n=18 per group) according to a random number table, including the control, model, low- (12.78 g/kg, BL group), medium- (25.65 g/kg, BM group), and high-dose BYHWD groups (51.30 g/kg, BH group). A rubrospinal tract transection model in rats was established, and different doses of BYHWD were intragastrically administrated for 4 weeks. The forelimb locomotor function was recorded using the spontaneous vertical exploration test. Cyclic adenosine monophosphate (cAMP) level in red nucleus was detected through an enzyme-linked immunosorbent assay. The morphology and number of red nucleus neurons were observed using Nissl's staining and axonal retrograde tracing by Fluoro-Gold (FG). The expression of cAMP-dependent protein kinase A (PKA), nuclear factor kappa-B (NF-κB) p65, and brain-derived neurotrophic factor (BDNF) in red nucleus were detected using immunohistochemistry and quantitative real-time polymerase chain reaction. RESULTS: Compared with the control group, the utilization rate of bilateral forelimbs, unilateral right forelimbs, proportion of FG-labeled positive neurons, cAMP level, protein expressions of PKA and BDNF, and BDNF mRNA expression were significantly decreased in the model group (P<0.01), while NF-κB p65 was increased in the model group (P<0.01). Compared with the model group, the utilization rate of bilateral forelimbs and unilateral right forelimbs were significantly higher in the BL, BM and BH groups (P<0.01), the proportion of FG-labeled positive neurons, cAMP level, protein expressions of PKA and BDNF and BDNF mRNA expression in all BYHWD groups were increased (P<0.05 or P<0.01), while NF-κB p65 were decreased in all BYHWD groups (P<0.05 or P<0.01). CONCLUSIONS BYHWD possesses a sound neuroprotective effect on red nucleus neurons after SCI, and the efficacy was dose-related. The mechanism may be related to regulating the cAMP/PKA/NF-κ B p65 signaling pathway, finally promoting expression of BDNF.
Animals ; Spinal Cord Injuries/pathology* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Male ; Cyclic AMP/metabolism* ; Transcription Factor RelA/metabolism* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Signal Transduction/drug effects* ; Brain-Derived Neurotrophic Factor/genetics* ; Red Nucleus/metabolism* ; Recovery of Function/drug effects* ; Neurons/metabolism* ; Rats

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the safety and effectiveness of single posterior osteotomy in the correction of rigid cervical spine deformities (CSD) and to explore the indications and key surgical techniques involved.Methods:A retrospective analysis was conducted on the clinical data of 9 patients with rigid CSD who underwent single posterior osteotomy correction between June 2012 and June 2023 in the Department of Spine Surgery at the First Affiliated Hospital of Xinjiang Medical University. The cohort comprised 4 males and 5 females, with a mean age of 19.8±27.2 years (range, 7-48 years). Among these, 5 cases were congenital CSD, 3 were post-tuberculosis deformities, and 1 was iatrogenic. Various coronal and sagittal alignment parameters were measured, including C 1, 2 angle, cervical lordosis (CL), structural scoliosis angle (SSA), structural kyphosis angle (SKA), head tilt (HT), C 2-C 7 sagittal vertical axis (CSVA), sagittal vertical axis (SVA), coronal balance distance (CBD), T 1 slope (T 1S), and the difference between T 1 tilt and cervical lordosis (T 1S-CL). Clinical outcomes were assessed using the neck disability index (NDI), visual analogue scale (VAS), and Scoliosis Research Society-22 questionnaire (SRS-22). Results:The average operation time was 273.9±76.1 min, with an average blood loss of 472.2±128.8 ml. All 9 patients were followed up for an average of 45.2±41.8 months (range, 12-116 months). A total of 7 patients underwent single-segment osteotomies (C 3, C 6 and C 7: 1 case each; C 5: 4 cases), and 2 patients underwent double-segment osteotomies (C 2 and C 7, C 3 and C 4). Four cases involved pedicle subtraction osteotomy (PSO), while 7 cases required vertebral column resection. The upper instrumented vertebra (UIV) was located at the occiput in 1 case and in the cervical spine in 8 cases. The lower instrumented vertebra (LIV) was located in the upper thoracic spine in 6 cases and in the cervical spine in 3 cases, with 2 of the latter cases having both UIV and LIV in the cervical spine. The average number of fused segments was 7.6±4.4 segments (range, 2-12 segments). All patients achieved successful bone fusion within an average of 8.8±3.2 months (range, 6-12 months). Preoperatively, the mean values for CL, SSA, SKA, HT, and CBD were 19.8° (17.2°, 30.5°), 27.4°(23.3°, 30.4°), 28.4°(25.6°, 30.1°), 9.0°(6.2°, 12.3°), and 18.5(12.3, 23.6) mm, respectively. Postoperative improvements were noted with values of -11.1°(-8.8°, -14.4°), 1.3°(0.8°, 1.6°), -11.1°(-8.6°, -14.5°), 1.6°(0.5°, 2.2°), and 9.4 (4.8-13.5) mm, respectively. At the final follow-up, these parameters were maintained, with values of -11.0°(-8.8°, -14.3°), 1.2°(0.8°, 1.5°), -11.0° (-8.6°, -14.3°), 1.5°(0.5°, 2.2°), and 9.4(4.8, 13.4) mm, respectively. Statistically significant improvements were observed between preoperative and postoperative measurements ( P<0.05), except for C 1, 2 angle, CSVA, SVA, T 1S, and T 1S-CL ( P>0.05). NDI and SRS-22 scores showed significant improvements postoperatively ( P<0.05), while VAS scores did not show a significant change ( P>0.05). Postoperative complications included transient nerve injury in two patients, one case of right central retinal artery occlusion, and one case of vertebral artery injury. Conclusion:This study confirms the safety and efficacy of single posterior osteotomy for treating rigid CSD of various etiologies. Standard PSO or modified techniques are effective for correcting cervical kyphosis, while hemivertebra resection and concave-side distraction are recommended for congenital scoliosis or kyphoscoliosis.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective To investigate the feasibility and value of a multi-parametric MRI radiomics-based nomogram model for pretreatment predicting the lymphovascular space invasion(LVSI)of endometrial endometrioid adenocarcinoma(EEA).Methods Preoperative MRI and baseline clinical characteristics of 205 EEA patients were prospectively collected from Oct 2020 to Jan 2022 in the Obstetrics and Gynecology Hospital,Fudan University,and randomly divided into training set(n=123)and validation set(n=82)in a 6∶4 ratio.The whole-tumor region of interest was manually drawn on T2-weighted imaging,diffusion-weighted imaging(apparent diffusion coefficient),and dynamic contrast-enhanced MRI,respectively,for radiomics features extraction.In the training set,univariate and multivariate Logistic regression analysis were used to select independent clinical predictors of LVSI(+)and construct the clinical model.The least absolute shrinkage and selection operator(LASSO)regression and multivariate Logistic regression analysis were used to select optimal radiomics features to form a radiomics signature.A combined nomogram model was established by integrating clinical independent predictors and the radiomics signature,and validated in the validation set.The predicting performance and clinical net benefit were evaluated by using the area under the receiver operating characteristic curve(AUC)and clinical decision curve analysis,respectively.Results Of the 205 EEA cases,144 cases were LVSI(-)and 61 cases were LVSI(+).Menopausal status,CA125,and CA199 were independent clinical predictors for the LVSI(+),and contributing to a clinical model with AUCs of 0.714(training)and 0.731(validation).From 8 240 extracted radiomics features,five were selected to construct a MRI radiomics signature after de-redundancy and LASSO dimensionality reduction,yielding AUCs of 0.860(training)and 0.759(validation).The combined nomogram model showed AUCs of 0.887(training)and 0.807(validation),outperforming others and achieving maximum clinical benefit in a large range of threshold probability in both training and validation sets.Conclusion The multi-parametric MRI-based nomogram model has the potential for pretreatment predicting the LVSI status of EEA,providing valuable information for clinical management decision-making and improving patient's clinical benefits.

Objective:To investigate the predictive value of cardiopulmonary exercise test (CPET) indexes for major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD).Methods:This study was a retrospective cohort study. CHD patients were consecutively enrolled who procedure CPET before discharge from the Department of Cardiology, General Hospital of Northern Theater Command from November 2015 to September 2021 were enrolled. Demographic information, past medical history, CPET indexes and other baseline data were collected and the patients were followed up. Patients were divided into a MACE group and a control group according to the presence or absence of MACE. A multivariate Cox proportional hazard regression model was used to analyze the CPET indexes with predictive value for MACE in CHD patients.Results:A total of 3 800 patients were eligible for the criterion, age (57.2±8.8) years, 2 920 (76.84%) males. During a follow-up of 1 237 (695, 1 596) days, 390 (10.26%) patients were in MACE group, and 3 410 (89.74%) patients were in control group. In adjusted multivariable analysis, higher metabolic equivalent of tasks (MET) at anaerobic threshold (AT) is an independent protective factor for MACE in patients with CHD ( HR=0.75, 95% CI 0.62-0.90, P=0.002), higher VE/VCO 2 is an independent risk factor for MACE in CHD patients ( HR=1.05, 95% CI 1.02-1.07, P=0.001). Conclusion:In CPET, high MET at AT is an independent protective factor for MACE in patients with CHD, and high VE/VCO 2 is an independent risk factor for MACE in CHD patients.

Objective:To investigate the changes in cardiopulmonary exercise testing (CPET) characteristics before and after the outbreak of COVID-19 in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).Methods:This is a cross-sectional study that included ACS patients who underwent PCI at the General Hospital of the Northern Theater Command from July 2018 to February 2023. Based on the timeline of the COVID-19 pandemic, patients were divided into two groups: the pre-pandemic group and the during-pandemic group, with January 2020 as the dividing line. Clinical data were collected from both groups, and a comparative analysis was performed on their postoperative CPET outcomes, including peak oxygen uptake (peak VO 2), peak metabolic equivalents (peak MET), and other indicators. Weber′s classification was used to assess cardiac function. In addition, the 7-tiem generalized anxiety disorder scale (GAD-7) and the patient health questionnaire-9 (PHQ-9) were used to assess the patients′ psychological anxiety and depression states, respectively. Multivariate logistic regression was used to analyze the influencing factors of CPET after PCI. Results:A total of 4 310 post-PCI ACS patients were included, with an average age of (58.7±9.1) years, and 3 464 (80.37%) were male. There were 1 698 patients in the pre-pandemic group and 2 612 patients in the during-pandemic group. The main indicator of the CPET, peak VO 2 (15.04±3.93) ml·min -1·kg -1 in the during-pandemic group, was lower than that in the pre-pandemic group (15.52±3.68) ml·min -1·kg -1, and the difference was statistically significant ( P<0.001). Multivariate logistic regression analysis showed that advanced age, female gender, high body mass index, elevated high-sensitivity C-reactive protein, reduced high-density lipoprotein cholesterol, smoking history, history of myocardial infarction, more severe ACS classification, and mild to moderate degree of depression were related to poor cardiopulmonary outcomes ( P<0.05). Conclusion:The COVID-19 pandemic had a negative impact on the cardiopulmonary outcomes of ACS patients after PCI. Reduced physical activity, and increased psychological stress should be given consideration and attention regarding their impact on patients′ cardiopulmonary function.