BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology* ; Humans ; Acute Lung Injury/immunology* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

OBJECTIVES: With the accelerating aging of the population and the rising prevalence of chronic diseases, the number of patients with pressure injuries (PIs) has increased markedly, prolonging the period of disease-related care. Informal caregivers play a critical role in the daily care of patients with pressure injuries, and their care burden has become increasingly prominent. This study aims to investigate the current status and influencing factors of care burden among informal caregivers of patients with PIs, providing evidence for targeted intervention strategies. METHODS: A total of 170 informal caregivers of patients with PIs were selected by convenience sampling from the Third Xiangya Hospital of Central South University. General demographic and clinical data of both patients and caregivers were collected. The Zarit Caregiver Burden Inventory (ZBI), Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, General Self-Efficacy Scale (GSES), and Family Caregiver Task Inventory (FCTI) were used to assess caregiving burden, knowledge-attitude-practice level, self-efficacy, and caregiving ability, respectively. Pearson correlation analysis was conducted to evaluate relationships among ZBI, Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, GSES, and FCTI scores. Stepwise multiple linear regression analysis was used to identify factors influencing caregiving. RESULTS: Among the 170 patients with pressure injuries, the age was (65.52±15.88) years; 118 (69.41%) were male and 52 (30.59%) were female. The duration of PIs was less than 1 month in 108 (63.53%) cases and 1 to 6 months in 40 cases (23.53%). Stage II injuries were predominant (135 cases, 79.41%). A total of 193 pressure injury sites were recorded, most commonly located at the sacrococcygeal region (127 sites, 65.80%), followed by the head (3 sites, 1.55%), shoulder and back (9 sites, 4.66%), feet (24 sites, 12.44%), and other regions (30 sites, 15.55%). Informal caregivers were 48.82% aged 46 to 59 years, 54.71% female, 41.77% primarily spouses and 47.06% children of the patients, and 77.06% lived with the patients. Caregivers who received assistance from others or had higher family per-capita monthly income reported significantly lower caregiver burden scores than those without assistance or with lower income (all P<0.001). The total ZBI score was 50.89±14.95, indicating a moderate burden. The total scores of the Knowledge-Attitude-Practice Scale for Informal Caregivers, GSES, and FCTI were 50.61±7.22, 26.03±7.11, and 14.76±8.70, respectively. Pearson correlation analysis revealed that ZBI scores were correlated with scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs (r=-0.543, P<0.001), GSES scores (r=-0.545, P<0.001), and FCTI scores (r=0.800, P<0.001). The scores on Knowledge-Attitude-Practice Scale for Informal Caregivers of patients with PIs were correlated with GSES scores (r=0.500, P<0.001) and FCTI scores (r=-0.461, P<0.001); GSES scores was negatively correlated with FCTI scores (r=-0.415, P<0.001). Stepwise multiple linear regression analysis showed that assistance availability, family per-capita monthly income, total scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, total GSES score, and total FCTI score were the main influencing factors of caregiver burden, jointly explaining 79.38% of its variance. CONCLUSIONS The main factors influencing the caregiving burden of informal caregivers of patients with PIs include the availability of assistance, family per-capita monthly income, total score on the Knowledge-Attitude-Practice Scale for Informal Caregivers of PI patients, total score on the GSES, and total score on the FCTI. Developing targeted intervention strategies addressing these factors may help alleviate the caregiving burden among informal caregivers of patients with PIs.
Humans ; Caregivers/psychology* ; Pressure Ulcer/nursing* ; Female ; Male ; Middle Aged ; Cost of Illness ; Adult ; Aged ; Surveys and Questionnaires ; Health Knowledge, Attitudes, Practice ; Self Efficacy ; Caregiver Burden ; China

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

ObjectiveBody fluid stains left at crime scenes are frequently trace amounts, while the identification of body fluids through real time fluorogenic quantitative technique often necessitates the repeated detection within the limited sample, as multiple miRNA markers are the basis for the identification. Based on the goal of both the throughput and efficiency improvement of miRNA analysis in trace samples, a duplex real time fluorogenic quantitative PCR assay system was designed to accurately quantify two miRNAs simultaneously, and the system should be further verified by actual sample for the body fluid identification. MethodsThe duplex real time fluorogenic quantitative PCR system of miR-451a to miR-21-5p was established with specially designed primers and probes, and the concentrations of the primers and probes were both optimized. The specificity, sensitivity and reproducibility of the system were validated, while its capability for body fluid identification was assessed using the miR-451a to miR-21-5p ratio. ResultsThe optimized assay system exhibited excellent specificity and repeatability, with coefficients of variation consistently below 8% for both intra- and inter-batch variability. The amplification efficiency of miR-451a and miR-21-5p reached 71.77% and 74.81%, respectively, with high and relatively consistent results. By utilizing this duplex real time fluorogenic quantitative PCR assay system, a total of 58 body fluid samples were analyzed, exhibiting a discrimination rate of 100% between blood and non-blood samples, as well as between peripheral blood and menstrual blood samples. Moreover, the results, obtained from single real time fluorogenic quantitative PCR assay system and duplex real time fluorogenic quantitative PCR assay system, showed no statistically significant difference with randomly selected blood samples (n=20). Compared to previous single real time fluorogenic quantitative PCR assay system, the sensitivity of duplex real time fluorogenic quantitative PCR assay system exhibited remarkable improvement. A minimum input of only 0.1 ng total RNA was sufficient for accurate detection of peripheral blood and menstrual blood samples, while saliva, semen, and vaginal secretion required only 1 ng total RNA for precise identification purposes. Additionally, the duplex real time fluorogenic quantitative PCR assay system successfully differentiated between different types of body fluids in simulated samples under natural outdoor conditions. ConclusionThe duplex real time fluorogenic quantitative PCR assay system effectively reduced both the time and material costs by half compared to the single system, especially suitable for the examination of body fluid stains left at crime scenes, solving the contradiction between the trace amount and the multiple sample volumes demand of repeated real time fluorogenic quantitative PCR. The duplex real time fluorogenic quantitative PCR assay successfully distinguished blood and other body fluid, as well as peripheral blood and menstrual blood samples, which maintains an equivalent capability for body fluid identification with half sample, time and reagent consumption. This system provides an efficient tool for identifying suspicious body fluids, as well as a foundation for more multiplexed real time fluorogenic quantitative PCR assay system research.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.

AIM To investigate the effects of stir-frying,processing with butter and carbonizing by stir-frying on oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis.METHODS The volatile oils and fatty oils were extracted by steam distillation method and Soxhlet extraction method,respectively,after which the extraction rates were determined.GC-MS was applied to analyzing the kinds and relative contents of oil components,after which cluster analysis was performed.RESULTS After the processing,the two medicinal materials demonstrated increased extraction rates of fatty oils and decreased extraction rates of volatile oils(except for processing with butter),the extraction rates of oil components in Gleditsiae sinensis Fructus were higher than those in Gleditsiae Fructus Abnormalis,and the reduced relative contents of toxic olefin benzene components were observable.CONCLUSION The kinds and relative contents of oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis exist obvious differences,the former displays better medicinal quality,whose processing mechanism in alleviating dryness and strength may contribute to the reduction of relative contents of toxic olefin benzene components.

Objective To explore clinical effect of different intervertebral fusion devices(cage)in treating postoperative recurrent lumbar disc herniation(LDH).Methods One hundred and forty-two LDH patients with recurrence after simple in-tervertebral disc nucleus pulpoideectomy from January 2019 to January 2021 were retrospectively analyzed.All patients were treated with combined underchannel fixation and interbody fusion and divided into a single anatomical group,two-anatomical group and a single banana group according to types and numbers of implanted cage.There were 51 patients in a single anatom-ical group,included 29 males and 22 females,aged from 39 to 65 years old with an average of(53.74±5.68)years old;body mass index(BMI)ranged from 18.62 to 28.13 kg·m-2 with an average of(22.08±2.15)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 4.0 years with an average of(2.7±0.8)years;5 patients with L3,4,35 patients with L4,5 and 11 patients with L5S1;a single anatomical cage was implanted.There were 46 patients in two-anatomical group,included 25 males and 21 females,aged from 37 to 66 years old with an average of(54.52±6.02)years old;BMI ranged from 18.25 to 28.44 kg· m-2 with an average of(21.74±1.83)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of(2.7±0.9)years;4 patients with L3,4,32 patients with L4,5 and 10 patients with L5S1;two-anatomical cages were im-planted.There were 45 patients in a single banana group,included 22 males and 23 females,aged from 38 to 65 years old with an average of(54.49±6.45)years old;BMI ranged from 18.85 to 28.20 kg·m-2with an average of(21.63±1.59)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of(2.6±1.0)years;3 patients with L3,4,36 patients with L4,5 and 16 patients with L5S1;a single banana cage was implanted.Operation time,intraoperative blood loss,incision length,postoperative incision drainage volume,hospital stay and complications among 3 groups were observed and compared.The height of intervertebral space before and after operation,curvature of lordosis and the postoperative interverte-bral fusion were compared.Visual analogue scale(VAS)and Oswestry disability index(ODI)were used to evaluate degree of lumbar pain and lumbar function before operation,1 and 6 months after operation,respectively.Results All patients among 3 groups were followed up at least 6 months,and no cases were fell out.There were no significant difference in operation time,in-traoperative blood loss,incision length,postoperative incision drainage volume and hospital stay among 3 groups(P＞0.05).At 6 months after operation,the height of intervertebral space in two-anatomical group and a single group were[(11.08±1.78)mm,(10.95±1.62)mm],curvature of lordosis were[(12.05±1.86)°,(11.63±1.57)°],which were higher than those in a sin-gle dissection group(10.14±1.54)mm,(10.92±1.45)°,and the difference were statistically significant(P＜0.05).The inter-body fusion rate between two-anatomical and a banana group(95.65％,95.56％)were higher than that in a single anatomical group(78.43％)at 6 months after operation(P＜0.05).VAS and ODI of lumbar among 3 groups were decreased at 1 and 6 months after operation(P＜0.05).There was no significant difference in complications among 3 groups(P＞0.05).Conclusion The three fusion devices could achieve significant results in treating postoperative recurrence of LDH,but the implantation of two-anatomical cage and a single banana cage are more helpful to maintain the height of intervertebral space and lordosis cur-vature of patients with postoperative recurrence of LDH,and obtain good intervertebral fusion results.