ObjectiveTo investigate whether anti-PD-1 monoclonal antibody can improve the efficacy and safety of cryoablation combined with lenvatinib in the treatment of unresectable hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for 232 patients with unresectable HCC who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2022， among whom 128 received cryoablation combined with lenvatinib （double combination） and 104 received cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody （triple combination）. Propensity score matching was performed at a ratio of 1∶1， and finally there were 86 patients in each group. The two groups were evaluated in terms of objective response rate （ORR）， disease control rate （DCR）， overall survival （OS）， progression-free survival （PFS）， and adverse events （AEs）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and 95% confidence interval （CI） and perform the univariate and multivariate analyses of influencing factors for prognosis. ResultsThe median follow-up time was 28 months， and there were 33 deaths （38.0%） in the triple combination group and 40 deaths （46.0%） in the double combination group. Compared with the double combination group， the triple combination group had significantly higher ORR （35.6% vs 14.5%， P=0.008） and DCR （86.1% vs 64.1%， P=0.003）. OS and PFS in the triple combination group were significantly higher than those in the double combination group （P=0.045 and 0.026）. The univariate and multivariate Cox proportional-hazards regression model analyses showed that treatment regimen （HR=0.60， P=0.038） and alpha-fetoprotein level （HR=2.37， P=0.001） were independent risk factors for OS， and treatment regimen （HR=0.65， P=0.025）， diabetes mellitus （HR=1.94， P=0.005）， whether or not to have received local treatment （HR=0.63， P=0.014）， and distant metastasis （HR=0.58， P=0.009） were independent risk factors for PFS. There was no significant difference in the incidence rate of AEs between the two groups （P>0.05）. ConclusionFor patients with unresectable HCC， the triple combination of cryoablation， lenvatinib， and anti-PD-1 monoclonal antibody significantly improves the treatment outcome and survival of patients compared with the double combination of cryoablation and lenvatinib， without increasing AEs， which provides a clinical basis for optimizing the treatment regimen for unresectable HCC.

Objective:To investigate the effect of macrophage-derived exosomes on the morphological transformation of Candida albicans (CA), and to explore the underlying mechanisms.Methods:In vitro cultured human acute monocytic leukemia cell line THP-1 was induced and differentiated into M0 macrophages using the phorbol ester PMA. CA was activated and prepared as the fungal suspension. M0 macrophages were infected with the CA suspension, and the process of cell phagocytosis was observed under a high-content imaging analysis system. M0 macrophage-derived exosomes (exosome group) and CA-infected M0 macrophage-derived exosomes (CA exosome group) were extracted by differential centrifugation; transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis were performed to identify and compare exosomes in the two groups. The exosomes from the two groups were separately co-cultured with CA (exosome-treated group and CA exosome-treated group), and independently cultured CA served as the blank control group; the morphological changes of CA were observed under an inverted microscope, the intracellular cyclic adenosine monophosphate (cAMP) contents were detected by the enzyme-linked immunosorbent assay (ELISA), and the expression levels of cAMP-related genes, RAS1 and CDC35 (also known as Cyr1), were detected by real-time quantitative PCR (RT-qPCR) . Results:Western blot analysis showed that exosomes from the exosome group and CA exosome group both expressed the tumor susceptibility gene 101 protein (TSG101, an exosome marker), and did not express calnexin (a negative marker) ; transmission electron microscopy and nanoparticle tracking analysis showed no significant differences in the morphology or size of the exosomes between the two groups. Compared with the blank control group, the exosome-treated group and CA exosome-treated group both showed obvious inhibition of the yeast-to-mycelial phase transition of CA, with a noticeable reduction in the length of the hyphae under the inverted microscope. ELISA revealed that the intracellular cAMP content in CA significantly decreased in the exosome-treated group and CA exosome-treated group (16.70 ± 0.84 pmol/ml, 16.82 ± 0.87 pmol/ml, respectively) compared with the blank control group (21.82 ± 1.08 pmol/ml; t = 6.45, 6.23, respectively, both P = 0.003). RT-qPCR revealed that the expression of the cAMP-related genes, RAS1 and CDC35, was down-regulated in the exosome-treated group and CA exosome-treated group compared with the blank control group (all P < 0.01), and the RAS1 mRNA expression was significantly lower in the CA exosome-treated group than in the exosome-treated group ( t = 7.43, P = 0.002) . Conclusion:Both M0 macrophage-derived exosomes and CA-infected M0 macrophage-derived exosomes could effectively inhibit the mycelial growth of CA, and the latter one exhibited a stronger inhibitory effect, possibly by down-regulating cAMP in the cAMP/protein kinase A pathway.

Objective To establish the reference intervals of neutrophil to lymphocyte ratio(NLR),mono-cyte to lymphocyte ratio(MLR)and platelet to lymphocyte ratio(PLR)in different genders and age groups in northern Chinese adults.Methods The data were analyzed according to the Clinical and Laboratory Stand-ards Institute C28-A3.Outliers were checked and judged according to the Dixon method.Subgroups were di-vided according to gender or age factors,and reference intervals were established for different subgroups.Ref-erence intervals were expressed as two-sided 95％percentiles.Results The reference intervals of NLR,MLR and PLR were 0.90-3.82,0.09-0.33 and 71.20-246.87,respectively.The results showed that NLR and PLR in men were lower than those in women(P＜0.001),while MLR in men was significantly higher than that in women(P＜0.001).Linear trend plots showed that NLR,MLR and PLR changed significantly in dif-ferent genders and age groups.In men,NLR and MLR increased with age,while PLR gradually increased and reached the peak before 50 years old,and gradually decreased after 50 years old.In women,NLR and MLR showed the lowest values at 50-＜60 years old,while PLR reached the peak at about 50 years old.The refer-ence intervals established by the model set were verified,and the percentages beyond the reference intervals were less than 10％in different genders and age groups.Conclusion The reference intervals of NLR,MLR and PLR in different genders and age groups of healthy adults in northern China are established in the study.

Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Objective To investigate the effect of Angelica polysaccharides on the balance of Th17/T-regulatory(Treg)cells and the expression of related inflammatory factor proteins in the bone marrow of mice with aplastic anemia.Methods 50 male BALB/c mice were randomly divided into a normal group,model group,cyclosporine A(CsA)group,and angelica polysaccharide low-(APS-L)and high-dose(APS-H)groups.A mouse model of aplastic anemia was prepared by combining irradiation with allogeneic lymphocyte infusion.After modeling,the mice were orally administered with corresponding drugs for 28 days.The general condition,weight changes,and spleen index of the mice were observed.Blood samples were taken to test for changes in basic hematological parameters of peripheral blood,and hematoxylin and eosin staining was used to evaluate the pathological changes in mouse bone marrow tissue.An ELISA method was applied to detect bone marrow TGF-β1.The expression levels of proteins such as IL-10,IL-17A,and IL-6 were analyzed,and flow cytometry was used in detecting the bone marrow Th17/Treg cell ratio.Results Compared with the normal group,the model group mice showed clumsiness during activity;lethargy;pale eyelids,lips,and ears;and reduced food and water intake.Both body weight and spleen index were significantly decreased.Peripheral red blood cell,white blood cell,and platelet counts and hemoglobin concentration were significantly reduced.A disordered bone marrow tissue structure and significantly reduced proliferation of hematopoietic tissue were seen.The expression of IL-17A and IL-6 proteins was significantly upregulated,and the expression of TGF-β1 and IL-10 protein was significantly downregulated.The proportion of Th17 cells in bone marrow significantly increased,the proportion of Treg cells significantly decreased,and the ratio of Th17/Treg cells significantly increased(P＜0.01).Compared with the model group,the general condition of the APS-L and APS-H groups improved,showing an increase in food and water intake;a significant increase in body weight and spleen index;a significant increase in peripheral red blood cells,white blood cells,platelets,and hemoglobin concentration(P＜0.05);an improvement in bone marrow tissue structure;and an increase in hematopoietic tissue proliferation(P＜0.05).The expression of IL-17A and IL-6 proteins was significantly downregulated.The expression of TGF-β1 and IL-10 protein was significantly upregulated(P＜0.05 or P＜0.01).The proportion of Th17 cells in bone marrow significantly decreased,the proportion of Treg cells significantly increased,and the ratio of Th17/Treg cells significantly decreased(P＜0.01).Conclusions Angelica polysaccharides can improve bone marrow hematopoietic function in aplastic anemia mice,and its mechanism of action may include the regulation of Th17/Treg cell balance.

BACKGROUND: Craniomaxillofacial tissue defects are clinical defects involving craniomaxillofacial and oral soft and hard tissues.They are characterized by defect-shaped irregularities, bacterial and inflammatory environments, and the need for functional recovery.Conventional clinical treatments are currently unable to achieve regeneration of high-quality oral craniomaxillofacial tissue. As a natural biomaterial, silk fibroin (SF) has been widely studied in biomedicine and has broad prospects for use in tissue regeneration.Hydrogels made of SF showed excellent water retention, biocompatibility, safety and the ability to combine with other materials. METHODS: To gain an in-depth understanding of the current development of SF, this article reviews the structure, preparation and application prospects in oral and craniomaxillofacial tissue regenerative medicine. It first briefly introduces the structure of SF and then summarizes the principles, advantages and disadvantages of the different cross-linking methods (physical cross-linking, chemical cross-linking and double network structure) of SF. Finally, the existing research on the use of SF in tissue engineering and the prospects of using SF with different cross-linking methods in oral and craniomaxillofacial tissue regeneration are also discussed. CONCLUSIONS This review is intended to show the advantages of SF hydrogels in tissue engineering and provides theoretical support for establishing novel and viable silk protein hydrogels for regeneration.

This article analyzed the laboratory indicators during the clinical diagnosis and treatment of two adolescents with mental disorders who developed rhabdomyolysis during hospitalization， so as to explore the risk of rhabdomyolysis occurring after mild to moderate exercise during treatment for adolescent with mental disorders and to provide references for clinical diagnosis and treatment.

Objective To observe the clinical efficacy of Jiangshabanxia nano-paste on nausea and vomiting in end-stage patients and its effect on the quality-of-life (QOL) in cancer patients. Methods 120 end-stage patients with nausea and vomiting symptoms above grade III were randomly divided into observation group and control group. They were treated with Jiangshabanxia nano-paste and placebo paste respectively. The paste patch was changed every 24 hours and used continuously for 7 days. The nausea and vomiting symptom score, the quality-of-life measurement score and KPS score of cancer patients in the two groups were observed to evaluate the curative effect. Results After 7 days of treatment, the symptom scores of nausea and vomiting in the observation group decreased significantly, the KPS score of the observation group increased, and the effective rate was higher than that in the control group. The score of QOL measurement showed that after treatment, the score of main symptom areas and other symptom areas (except external dyspnea, diarrhea and economic difficulties) in the observation group decreased, and the score of overall health area increased. After treatment, the score of main symptom areas and other symptom areas (except external dyspnea, diarrhea and economic difficulties) in the observation group was lower than that in the control group, and the scores of overall health area in the observation group were higher than those in the control group. Conclusion Jiangshabanxia nano-paste has a good clinical efficacy nausea and vomiting in end-stage patients, it also can improve the quality of life end-stage cancer patients.

Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.

Abstract OBJECTIVE To clarify the resource status and diversity of endemic medicinal plants in Shaanxi province. METHODS The species specificity, species composition, faunal composition, family and genus types, medicinal value and endangerment degree of endemic medicinal plants in Shaanxi province were studied by literature review.RESULTS There were 713 species of 331 genera and 101 families endemic to Chinese medicinal plants in the study area. Fifteen species were naturally distributed only in Shaanxi province, and the remaining 698 species were also naturally distributed in other provinces of China. Among the 713 species, 233 species(69 families, 159 genera) were not collected from the fourth resource census in Shaanxi province. There were 11 species of pteridophytes in 7 families and 11 genera, 14 species of gymnosperms in 4 families and 10 genera, 627 species of dicotyledons in 82 families and 278 genera, and 59 species of monocots in 8 families and 32 genera. The endemic life forms of medicinal plants in the study area were mostly herbaceous, followed by shrubs and trees, and semi-shrubs and epiphytes accounted for the least. There were 9 families with ≥ 20 species and 4 families with ≥ 10 species in the study area. The 90 families belonging to the endemic species of medicinal plants in Shaanxi province were divided into 13 distribution types and 9 variations, and the tropical distribution(2-7 categories) had a total of 34 families. There were 5 endemic species of medicinal plants in the study area under the national class I key protection, and 14 species under the national class II key protection. There were 26 species of plants under local key protection in Shaanxi province. There were 21 plants that could be used as original plants for medicinal materials included in the Pharmacopoeia of the People's Republic of China(2020 edition). CONCLUSION The endemic species of medicinal plants in Shaanxi province are rich in resources and have good medicinal value. However, the growing environment of some plants is harsh and human damage is serious. Multiple protection measures should be taken to maintain the species diversity and sustainable development of resources in the study area.