OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

AIM:To explore the efficacy of lenvatinib(Len)in enhancing the therapeutic effects of immune checkpoint inhibitor for hepatocellular carcinoma(HCC)and to delve into its immunomodulatory mechanisms within the tumor microenvironment.METHODS:The effects of various concentrations of Len on the migration of human umbilical vein endothelial cells(HUVECs)and the secretion of CXC chemokine ligand 10(CXCL10)were investigated,and the mechanism by which Len modulates CXCL10 secretion was validated.An orthotopic HCC model was established,and the mice bearing tumors were randomly allocated into 4 groups:PBS group,BMS-202(PD-1/PD-L1 inhibitor)group,Len group,and Len/BMS-202 group.The progression of the orthotopic liver tumors was monitored with small animal in vivo im-aging techniques.On the 13th day after the treatment,mice were sacrificed and tumor tissues were harvested for analysis.Immunofluorescence was employed to identify apoptosis,vascular architecture,and hypoxic status within the tumor tis-sue.The expression levels of proliferation marker Ki67,transforming growth factor-β(TGF-β),and the infiltration de-grees of CD4+T cells and CD8+T cells in the tumor tissue were monitored with immunohistochemistry.The secretion of im-mune factors interferon-γ(IFN-γ),CXCL10 and TGF-α in the mouse serum was quantified with ELISA.Above all data were followed by statistical analysis.RESULTS:(1)Len could facilitate endothelial cell migration within a specific range and potentiated the response of tumor cells to IFN-γ by blocking fibroblast growth factor receptor(FGFR),thereby increasing the secretion of CXCL10 from the tumor cells.(2)Compared with PBS group,tumor growth was slower in all treatment groups,with Len/BMS-202 group showing the most significant inhibition of tumor growth in tumor-bearing mice(P<0.05).(3)Compared with PBS group and monotherapy groups,Len/BMS-202 significantly promoted tumor tissue apoptosis and inhibited tumor cell proliferation(P<0.05).(4)Compared with PBS group and BMS-202 group,both Len group and Len/BMS-202 group manifested a substantial enhancement in pericytes coverage rate(P<0.01),concomitantly showing a marked improvement in hypoxic conditions(P<0.01).(5)Compared with PBS group and monotherapy groups,Len/BMS-202 group showed a significant increase in the infiltration of CD4+T cells and CD8+T cells within the tumor(P<0.01),along with a marked decrease in the expression of TGF-β(P<0.01).(6)Compared with PBS group,all treatment groups collectively induced varying degrees of secretion of IFN-γ,CXCL10 and TGF-α in mouse serum(P<0.05),with Len/BMS-202 group demonstrating the most pronounced effects(P<0.01).CONCLUSION:Lenvatinib may augment the therapeutic efficacy of BMS-202 in HCC by facilitating tumor vascular normalization,alleviating hypoxic conditions,and enhancing the secretion of CXCL10,thereby synergistically activating the tumor immune microenvironment.

Purpose To explore the ultrasound features and early diagnostic clues of fetal myocardial non-compaction.Materials and Methods The clinical data and echocardiographic data of four fetuses who underwent fetal echocardiography in Henan Provincial People's Hospital from January 2015 to February 2023 and were confirmed to have myocardial non-compaction by pathological finding or postnatal examination were collected,and analyzed.Results A total of four fetuses diagnosed as myocardial non-compaction by prenatal ultrasound:two involved the left ventricle with isolated lesions,and apical myocardial non-compaction was confirmed by postnatal echocardiography;two involved the biventricles,and both of which were pathologically confirmed after induction of labor.The prenatal ultrasound of fetal myocardial involvement in four cases showed that:(1)the affected myocardium showed a bilayer structure:the outer layer was compacted myocardium,which showed thin and compacted homogeneous hypoechoic;the inner layer was loose and thickened non-compacted myocardium with enhanced echogenicity;(2)color Doppler flow imaging:the non-compacted myocardium showed sieve mesh blood flow with ventricular communication.Some cases were associated with cardiac enlargement and arrhythmia.Conclusion Prenatal echocardiography can diagnose fetal myocardial non-compaction with a characteristic echographic presentation.Localized myocardial thickening and echogenic enhancement,cardiac enlargement and arrhythmia may be important clues to identify fetal myocardial non-compaction.

ObjectiveTo explore the comprehensive clinical value of Qianlieping capsules in the treatment of chronic prostatitis with damp-heat stasis syndrome， and to provide evidence for the decision-making of clinical basic drug management. MethodBased on the "Guidelines for Comprehensive Clinical Evaluation of Drugs （Trial Version 2021）"， this study systematically reviewed the existing research on the treatment of chronic prostatitis with damp-heat stasis syndrome by Qianlieping capsules. Based on evidence-based medicine， clinical epidemiology， clinical medicine， evidence-based pharmacy， pharmacoeconomics， health statistics， health technology assessment， and other disciplines， the multi-criteria decision analysis model （MCDA） and CSC 2.0 software were used. The six dimensions of safety， effectiveness， economy， innovation， suitability， and accessibility of drugs， as well as traditional Chinese medicine（TCM） characteristics， were comprehensively evaluated qualitatively and quantitatively. ResultIn terms of safety， based on the spontaneous reporting system （SRS） of the National Center for ADR Monitoring， safety literature analysis， pharmacological and toxicological experiment report， and other evidence， the safety grade of Qianlieping capsules was evaluated as grade A， with good safety. In terms of effectiveness， based on the results of pharmacological and pharmacodynamic studies and Meta-analysis， and combined with the value and quality of the evidence for efficacy， the final efficacy grade of Qianlieping capsules was rated as B. In terms of economy， Qianlieping capsules was a class B drug of national medical insurance. Compared with those of similar Chinese patent medicines， the average daily cost of Qianlieping capsules was moderate， and there was no related cost increase during the administration process. Economic research showed that Qianlieping capsules combined with α-receptor blockers were more economical than α-receptor blockers alone. Based on the quality evaluation of economic evidence and the value evaluation of economic evidence， the economic grade of Qianlieping capsules was rated as B. In terms of innovation， Qianlieping capsules were a combination of cold and warm drugs， focusing on clearing heat， detoxifying， removing blood stasis， and relieving pain， with non-toxic medicinal materials. They obtained a number of invention patents. The enterprise service system was perfect， and the quality standard was higher than the international and Chinese standards. The innovation grade of Qianlieping capsules was rated as B. In terms of suitability， the results of the questionnaire survey showed that it had relatively good suitability for clinicians， nurses， pharmacists， and patients who used Qianlieping capsules. The information on Chinese patent medicines was complete and met the requirements of national standards. The suitability grade of Qianlieping capsules was rated as A. In terms of accessibility， Qianlieping capsules were moderately priced and affordable， with sufficient resources of medicinal materials， no shortage of medicinal materials， and good availability. The accessibility grade of Qianlieping capsules was rated as B. In terms of TCM medicine characteristics， the prescription of Qianlieping capsules was derived from Danshen Huoxue Decoction. The original prescription was used for the treatment of chronic prostatitis with blood stasis syndrome. The whole formula was recorded in The Complete Compendium of Fine Formulas （《良方大全》） published by Beijing Publishing Group Co.， Ltd. in 1991 and has been used for more than 30 years. The formula was a combination of warm and cold drugs， attacking pathogens without hurting healthy Qi. The grade of TCM characteristics of Qianlieping capsules was rated as B. ConclusionBased on the above "6+1" dimensions， the comprehensive evaluation result of Qianlieping capsules in the treatment of chronic prostatitis with damp-heat and blood stasis syndrome is grade B， and it is recommended to convert it into the relevant policy results of basic clinical drug management according to the conditions.

Lung cancer is the most common in incidence and mortality worldwide. With the development of next generation sequencing (NGS) detection technology, more and more patients with rare anaplastic lymphoma kinase (ALK) fusion mutations were detected. A case of advanced lung adenocarcinoma with rare COX7A2L-ALK (C2:A20) fusion detected by NGS was reported in Peking Union Medical College Hospital, and all cases with rare ALK fusion mutations were searched from medical datebase from January 1, 2014 to March 31, 2021, to investigate the treatment of rare ALK fusion mutations with ALK inhibitors. The best response of the patient was assessed as partial response (PR) with Ceritinib treatment. By literature review, 22 cases of rare ALK fusion were reported in 19 articles. Combined with this case, 23 cases were analyzed. The objective response rate (ORR) was 82.6% (19/23) and disease control rate (DCR) was 95.7% (22/23) for rare ALK fusions patients treated with ALK inhibitors. Lung adenocarcinoma patients with rare ALK fusion could benefit from ALK inhibitors.
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Humans ; Anaplastic Lymphoma Kinase/genetics* ; Lung Neoplasms/diagnosis* ; Crizotinib ; Adenocarcinoma of Lung/genetics* ; Protein Kinase Inhibitors/pharmacology* ; Oncogene Proteins, Fusion/genetics*

ObjectiveTo evaluate the efficacy and safety of An'erning granules in the treatment of community-acquired pneumonia in children. MethodA randomized， double-blind， single-simulation， placebo-controlled trial was designed in this study. The children were randomly assigned into an observation group （An'erning granules combined with ceftriaxone sodium） and a control group （An'erning granules placebo combined with ceftriaxone sodium） according to the ratio of 2∶1. The disease cure rate was taken as the main indicator of efficacy， and the safety of An'erning granules was observed. ResultA total of 206 children （137 in the observation group and 69 in the control group） were included in this study. Before treatment， the age， sex， body height， body weight， diagnosis time of pneumonia， and symptom and sign scores had no significant differences between the two groups. After 8 days of continuous medication， the observation group［70.80%（97/137）］ had higher cure rate than the control group［56.52%（39/69）］（χ²=4.17，P<0.05） and total effective rate of chest X-ray ［97.98%（97/99）］ than the control group［86.27%（44/51）］ （χ²=12.98，P<0.01）. The observation group was superior to the control group in the alleviation of TCM syndrome under the condition of 0-3 g dose stratification on day 3 of medication （P<0.01）. The recovery time， time to complete fever abatement， time to fever abatement and expectoration alleviation， rate of conversion to severe case， and reduction in the frequency of antibiotic use showed no significant differences between the two groups. In terms of safety， 13 and 7 adverse events occurred in the observation group and control group， respectively， which were relieved or disappeared after drug withdrawal or symptomatic treatment and showed no significant difference between the two groups. ConclusionIntravenous drip of ceftriaxone sodium combined with An'erning granules is effective in the treatment of community-acquired pneumonia in children. It can accelerate the absorption of pulmonary inflammation， alleviate the clinical symptoms in a short time for young children or the children with mild symptoms， and is safe in clinical application.

Objective:To investigate the prognostic significance of D-dimer level in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 70 newly diagnosed DLBCL patients who were admitted to Tianjin People's Hospital from January 2015 to June 2019 were retrospectively analyzed. The optimal cut-off value of D-dimer for survival was determined according to the receiver operating characteristic (ROC) curve, and the patients were grouped. The differences of coagulation related indexes and clinicopathological features between patients with different D-dimer levels were compared. Kaplan-Meier method was used for univariate analysis of overall survival (OS), and Cox regression model was used for multivariate analysis of OS.Results:According to ROC curve, the best cut-off value of D-dimer for survival was 0.75 mg/L. The proportion of patients with different clinical staging, international prognostic index score, lactate dehydrogenase level had statistically significant differences between the D-dimer ≥0.75 mg/L group (36 cases) and <0.75 mg/L group (34 cases) (all P < 0.05). The prothrombin time of D-dimer ≥ 0.75 mg/L group and < 0.75 mg/L group were (13.5±0.9) s and (13.0±0.8) s, respectively, and the activated partial thromboplastin time were (37±5) s and (34±6) s, respectively,and the differences were statistically significant (all P < 0.05). Univariate analysis showed that the 5-year OS rates of DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ, international prognostic index score > 2, lactate dehydrogenase level > 240 U/L, B symptoms, D-dimer level ≥0.75 mg/L were decreased (all P < 0.05). Multivariate Cox regression analysis showed that D-dimer ≥0.75 mg/L was an independent risk factor for OS of DLBCL patients ( HR=0.368, 95% CI 0.144-0.944, P= 0.038). Conclusion:The level of D-dimer can be used as a clinical indicator to judge the prognosis of DLBCL patients, and the prognosis of patients with high D-dimer level is poor.

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.

Objective:To explore the effect of expressive writing in young and middle-aged patients with colorectal cancer, so as to provide a basis for clinical intervention.Methods:From January to November 2019, convenience sampling was used to select 92 young and middle-aged colorectal cancer patients who underwent surgery in the First Affiliated Hospital of Guangxi Medical University as the research objects. Patients were divided into control group ( n=48) and observation group ( n=44) by the random method. Patients in control group received routine care during hospitalization for patients with colorectal cancer, and patients in observation group added expressive writing intervention on the basis of routine care. The Profile of Mood State-Short Form (POMS-SF) , Meaning in Life Questionnaire (MLQ) , Pittsburgh Sleep Quality Index (PSQI) were used to evaluation one to two days after admission and one day before discharge. Results:A total of 44 valid questionnaires were returned in control group and 43 valid questionnaires in observation group. After intervention, there were statistical differences in the dimension scores of tension-anxiety, depression-frustration, fatigue-indulgence, confusion-mull and energy-vigor in POMS-SF of patients between two groups ( P<0.05) . After intervention, the scores of the sense of meaning of life and searching for the meaning of life in the MLQ of observation group were higher than those of control group, and the differencs were statistically significant ( P<0.05) . There was no statistically significant difference in PSQI scores between two groups before and after intervention ( P>0.05) . Conclusions:Expressive writing has a positive effect on improving negative emotions and sense of meaning in life for young and middle-aged patients with colorectal cancer.

OBJECTIVE： To study the mechanism of analgesic effect of 8-O-acetyl-safalinoside （8-OaS） on chronic inflammatory pain model rats. METHODS ：Totally 30 male SD rats were divided into sham operation group （normal saline ）， model group （normal saline ），8-OaS low-dose ，medium-dose and high-dose groups （3，10，30 μg/kg），with 6 rats in each group. Except for sham operation group ，other groups were given planter injection of Freund ’s complete adjuvant to induce chronic inflammatory pain model. After successful modeling ，the rats in each group were given corresponding drugs intrathecally ，once a day，for 7 consecutive days. Then Von-Frey filaments were used to detect the planter pain threshold of the rats in each group ；the area under the planter pain threshold curve of each group and the half effective dose （ED50）of 8-OaS were calculated. Another 36 male SD rats were divided into sham operation group （normal saline ），model group （normal saline ）and 8-OaS group （dose of ED50），and the modeling method and administration route were the same as above. Immunofluorescence histochemical staining was used to observe the positive expression of ionized calcium binding adapter molecule 1（Iba-1）and signal molecule phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）；Western blotting assay was used to determine the expression of Iba- 1，p-p38 MAPK，IL-1β，IL-6 and TNF-α in spinal dorsal horn of rats. RESULTS：Compared with sham operation group ，plantar pain threshold and area under the curve in model group were reduced significantly （P＜0.01）. Compared with model group ，plantar pain threshold increased significantly after 5，6，7 days of administration in 8-OaS low-dose group （P＜0.05），plantar pain threshold and area under the curve in 8-OaS medium-dose and high-dose groups were increased significantly （P＜0.05 or P＜0.01）. Most of above indexes in each dose group of 8-OaS were signifficantly different ，and ED 50 of 8-OaS was 18.87 μ g/kg. Results of immunohistochemistry staining and Western blotting showed that p-p 38 MAPK was mainly expressed in Iba- 1 positive cells. Compared with sham operation group ，the fluorescence density of Iba- 1 and p-p 38 MAPK in spinal dorsal horn ，the expression of Iba-1，p-p38 MAPK，IL-6，IL-1β and TNF-α were significantly increased in model group（P＜0.05 or P＜0.01）. Compared with model group ，the fluorescence density of Iba- 1 and p-p 38 MAPK in spinal dorsal horn ，the expression of Iba- 1，p-p38 MAPK， IL-6，IL-1β and TNF-α were decreased significantly in 8-OaS group （P＜0.05）. CONCLUSIONS ：Intrathecal administration of 8-OaS can effectively alleviate chronic inflammatory pain in rats. The mechanism may be related to the inhibition of the phosphorylation of p 38 MAPK and the expression of IL- 6，IL-1β and TNF-α.