ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Objective:To compare the efficacy of surgical resection and radiofrequency ablation (RFA) treatment for China liver cancer staging (CNLC) Ia hepatocellular carcinoma (HCC) at difficult-to-reach locations.Methods:A retrospective analysis was conducted on the clinical data of 114 patients with CNLC Ia HCC at Ⅶ、Ⅷ、Ⅳb or Ⅰ segments that were difficult-to-reach locations who were admitted to People's Hospital of Zhengzhou University from December 2018 to December 2023. Among the patients, 85 were males and 29 were females, aged (58.1±1.0) years. The patients were divided into two groups: a RFA group with 31 cases and a surgical resection group with 83 cases. Compare the levels of alanine transaminase (ALT) and aspartate transaminase (AST) before and after surgery, the surgical time, intraoperative blood loss, postoperative hospital stay, postoperative complications, recurrence free survival rate, and cumulative survival rate between the two groups.Results:The comparison of age, gender, ALT, and AST between the two groups showed no statistically significant differences (all P>0.05). The differences in ALT and AST levels before and after surgery in the RFA group were (134.8±38.7) U/L and (195.1±53.9) U/L, respectively, which were significantly lower than those in the surgical resection group [(226.8±17.9) U/L and (229.5±16.2) U/L] ( t=-2.45 and -1.12, P=0.016 and 0.041). The RFA group had shorter operation time [(69.2±11.7) min vs. (210.6±8.9) min], less intraoperative blood loss [(8.7±3.8) ml vs. (238.6±20.8) ml], and shorter postoperative hospital stays [(6.4±1.0) d vs. (13.1±0.4) d] compared to the surgical resection group, with all differences statistically significant (all P<0.05). The overall complication rates were 19.4% (6/31) in the RFA group and 22.9% (19/83) in the surgical resection group, showing no significant difference ( χ2=0.16, P=0.685). No statistically significant diffe-rence was found in recurrence-free survival rates between the two groups ( χ2=0.13, P=0.717). Similarly, there was no statistically significant difference in cumulative survival rates between the groups ( χ2<0.01, P=0.978). Conclusion:For HCC at CNLC Ⅰa in challenging locations, RFA demonstrated shorter operation time and postoperative hospital stay, less intraoperative bleeding, and superior liver function recovery compared with surgical resection, while no significant difference was observed in survival outcomes between the two treatment groups.

Objective To investigate the inhibitory effect of erianin on T cell proliferation and its underlying mechanism.Methods Peripheral blood mononuclear cells(PBMCs)were isolated using density gradient centrifugation,and T cells were purified by magnetic-activated cell sorting(MACS)with immunomagnetic beads,followed by being activated with anti-human CD3 antibodies and anti-human CD28 antibodies.The activated T cells were labeled with carboxyfluorescein succinimidyl ester(CFSE),and the effects of erianin(0.05～0.20 μmol/L)on the proliferation,apoptosis,expression of activation marker cluster of differentiation 25(CD25),cell cycle distribution of activated T cells,as well as the survival rate of resting T cells were assessed using flow cytometry.Enzyme-linked immunosorbent assay(ELISA)was applied to determine the secretion levels of IL-2 and IL-17 in the culture supernatant of erianin-treated activated T cells.Western blotting was employed to examine the impact of erianin on the protein expression of cell division cycle protein 2(CDC2),phosphorylated CDC2(p-CDC2),and Cyclin B1.The differences were observed between the erianin-treated group and the positive control group(activation with CD3/CD28 antibodies).Results CFSE proliferation assay demonstrated that the proliferative rate of activated T cells was in a concentration-dependent decline after 0.05～0.20 μmol/L erianin treatment(P<0.0001),with a half-maximal inhibitory concentration(IC50)of 0.09±0.10 μmol/L.No significant differences were observed in apoptotic rates or survival rates among the erianin-treated groups(activated and resting T cells)and the positive control cells.Analysis of T cell activation markers revealed that erianin had no impact on CD25 expression or IL-2 secretion.However,ELISA results indicated erianin exerted a significant suppression on the secretion of pro-inflammatory cytokine IL-17(P<0.0001).Cell cycle analysis showed that erianin arrested activated T cells at the G2/M phase(P<0.05).Further mechanistic investigations demonstrated that while erianin did not alter CDC2 phosphorylation or total CDC2 expression,but it markedly down-regulated CyclinB1 expression(P<0.01).Conclusion Erianin exhibits potent immunomodulatory activity by suppressing activated T cell proliferation through down-regulating Cyclin B1.

Reasonable and standardised placebo setting for acupoint application pastes is a key factor for clinical trials to verify the safety and effectiveness of acupoint application. By sorting out the current design status of placebo in the allocation concealment and blind design， paste components， paste location， paste duration in the current clinical trials of acupoint application pastes， it is proposed that there are problems such as low application rate of blinding and non-standardised reporting， insufficient standardisation of placebo settings and lack of systematic research， and lack of uniform standards of the placebo evaluation method. Based on the action mechanism of acupoint application， the idea of setting placebo for acupoint application paste is proposed in terms of replacing the application material， controlling the physicochemical effect produced by transdermal absorption of drugs， and setting the permeability of placebo， in order to enrich the methodological content of the placebo setting for acupoint application， and providing more scientific and reliable clinical evidence of acupoint application.

Immune checkpoint inhibitors(ICIs)represent the most widely used immunotherapeutic approach for antitumor treatment,yet the understanding of their associated hepatotoxicity remains incomplete.This article delves into and analyzes the similarities and differences among the management guidelines on ICI-related hepatotoxicity issued by the Chinese Society of Clinical Oncology(CSCO),the National Comprehensive Cancer Network(NCCN)of the United States,and the American Society of Clinical Oncology(ASCO),aiming to provide a more comprehensive management strategy for clinical practice.By reviewing and analyzing the latest guidelines,this study compares the differences and similarities in the diagnosis,assessment,grading criteria,and treatment strategies for ICI-related liver toxicity among these guidelines.The definitions and diagnostic criteria for ICI-related liver toxicity are generally consistent across different guidelines,primarily relying on the elevated levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),bilirubin,and alkaline phosphatase(ALP)for grading.Notably,the ASCO guidelines place a stronger emphasis on the assessment of symptoms of hepatic dysfunction.In terms of treatment strategies,all guidelines recommend using corticosteroids or immunosuppressants based on the toxicity grade.However,there are discrepancies in management strategies among the guidelines.Clinicians should tailor management strategies by considering the specific conditions of patients and integrating the recommendations from various guidelines.Additionally,given the current inadequate understanding of ICI-induced hepatotoxicity primarily manifested as cirrhosis in the existing guidelines,it is imperative to continuously update and refine these management guidelines as research progresses and clinical experience accumulates.

Purpose Discover new prostate cancer-related single nucleotide variants.Methods Tissue wax blocks from 21 prostate cancer patients who underwent radical surgery and had relatively complete clinical data were collected for somatic mutation detection to analyze new mutated genes associated with prostate cancer.The levels of cor-responding proteins in the urine of prostate cancer patients were tested according to the results of the selected genes.Results All 21 prostate cancer patients showed obvious somatic mutations,and the mutation types were dominated by C＞T and G＞A.The number of somatic mutations was 521,of which 27 genes had high mutation proportions(≥2 ca-ses),including ZSWIM6(5/21),FOXA1(4/21),SPTA1(2/21),FAM47C(2/21),FLG2(2/21),PRSS3(2/21),TP53(2/21),FLG(2/21),UBR4(2/21),and the mutations occurring in ZSWIM6 were all deletion muta-tions,and the mutations occurring in FOXA1 were missense mutations,deletion mutations,and deletion insertion mu-tations.The urinary levels of UPF1,SPTA1,and IDH1 proteins of the 10 prostate cancer patients were significantly different than those of the healthy controls.Correlation analysis showed that FOXA1 was positively correlated with UBR4(r=0.669,P=0.001),SPTA1 was positively correlated with FLG2(r=1.000,P＜0.001),FAM47C was positively correlated with PRSS3(r=1.000,P＜0.001),and there was a significant positive correlation between TP53 and FLG(r=1.000,P＜0.001).ZSWIM6 and FOXA1 were not correlated with biochemical recurrence.SP-TA1 mutation affected progression-free survival(PFS)[(66.0±0)months vs(30.0±7.8)months,P=0.008].FAM47C was positively correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].ZNF676 was correlated with PFS[(66.0±0)months vs(26.0±5.0)months,P=0.008].FLG2 was correlated with PFS[(66.0±0)months vs(30.0±7.8)months,P=0.008].PRSS3 was correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].Conclusion All 21 prostate cancer patients harbored somatic mutations,including ZSWIM6(5/21)and FOXA1(4/21)mutations.SPTA1,FAM47C,ZNF676,FLG2,and PRSS3 may be associated with prognosis.

Based on the theory of circulation of qi,a theoretical model of the circulation of phase fire in the human body was con-structed.It is proposed that cancer toxicity is the key factor that triggers the disorder of phase fire and hinders the circulation of phase fire.The disorder of phase fire and poor circulation are important pathogenesis of the occurrence and development of cancer toxicity.With the principle of strengthening healthy qi and eliminating evil qi,the Wenzi Jiedu method is used to treat tumors,which plays an important role in warming and nourishing,regulating yin and yang,and eliminating cancer toxicity.The combination of war-ming,nourishing and detoxification can promote the return of the phase fire and make the human body's generation and transformation active,providing a new treatment idea for TCM diagnosis and treatment of tumors with mainly cold poison or mixed cold and heat.

Objective:To investigate changes in the density and spatial distribution of CD69 + T cells within hepatocellular carcinoma tissues following immune checkpoint blockade (ICB) therapy, and to explore their correlation with tumor infiltrating immune cell. Methods:Tumor specimens were collected from 12 patients with hepatocellular carcinoma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of People's Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from July 2023 to July 2024. There were 10 males and 2 females, aged (58.5±5.6) years. Of the 12 patients, 6 cases underwent radical surgery directly and 6 underwent radical surgery after immunotherapy. The maximum tumor diameter and tumor volume of the immunotherapy group were measured by imaging. The density and distribution of immune cells such as CD8 + CD69 + T, CD4 + CD69 + T and programmed death-1 (PD-1) were detected by immunohistochemistry and immunofluorescence. The number of immune cells around the target cells was calculated to evaluate the effective score, and the intercellular distance was measured to evaluate the intercellular interaction. Results:The maximum tumor diameter and tumor volume of 6 patients after immunotherapy were lower than before treatment, and the differences were statistically significant (all P<0.05). The density of PD1 + cells in the immunotherapy group was 36.6 (25.9, 55.9) cells/mm 2, which was less than that in the control group 53.9 (38.3, 84.5) cells/mm 2, and the difference was statistically significant ( Z=-2.66, P=0.008). In the control group, the number of CD8 + CD69 + T cells was positively correlated with CD8 + PD1 + T cells and CD8 + PD1 + CD103 + T cells, and the correlation coefficients were 0.42 and 0.40, respectively ( P=0.001, 0.002). The effective scores of CD8 + CD69 + T cells and CD8 + PD1 + T, CD4 + CD103 + T, CD4 + PD1 + CD103 + T and CD8 + PD1 + CD103 + T cells in the above three areas in the immunotherapy group were lower than those in the control group, with statistical significance (all P<0.05). The distance between CD8 + CD69 + T and CD4 + CD69 + CD103 + T cells in the interface area of the control group was closer than that of the immunotherapy group, and the difference was statistically significant ( t=2.67, P=0.009). Conclusion:After immunotherapy in hepatocellular carcinoma patients, PD-1+ cells and immune cells around CD8 + CD69 + T cells decreased, and this change was related to the distance between CD8 + CD103 + T cells.

Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.H uman non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antivi-ral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein syn-thesis,and virus particle formation(all P＞0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P＜0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert anti-viral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.

Objective:To evaluate the effectiveness and safety of thulium fiber laser enucleation of the prostate(ThuFLEP)in the treatment of oversized(＞200 mL)prostate.Methods:Clinical data of 475 benign prostatic hyperplasia(BPH)patients operated by the same urologist at Peking University First Hospital from January 2022 to May 2024 were retrospectively analyzed,all of whom were treated with thu-lium fiber laser,and the patients were divided into three groups according to the total volume of the pros-tate(TPV):group A(TPV＜100 mL),group B(100 mL≤TPV＜200 mL),and group C(TPV ≥200 mL).The age of the patients in the three groups[(69.38±7.79)years,(69.64±8.69)years,(70.32±7.44)years],International Prostate Symptom Score(IPSS)[(22.7±1.9),(22.8±2.7),(25.8±3.7)],and the maximum urinary flow rate(Qmax)[(7.9±2.7)mL/s,(9.3±4.3)mL/s,(9.9±3.3)mL/s]were not statistically significant(P＞0.05).The prostate volume in the three groups[(103.49±46.19)mL,(75.73±30.69)mL,(273.49±49.19)mL]and prostate specific antigen(PSA)[3.52(1.05,8.76)μg/L,6.78(1.61,7.45)μg/L,8.52(5.05,12.76)μg/L]were statistically significant(P＜0.05).Results:All surgeries were successfully completed.The dif-ferences in enucleation time[30.0(21.2,44.5)min,41.6(31.2,52.5)min,45.1(35.2,50.0)min]and hospitalization time[(6.06±1.21)d,(6.15±1.50)d,(7.71±1.74)d]among the three groups were not statistically significant(P＞0.05);and the differences in the postoperative in-dwelling catheter time[(4.0±1.4)d,(4.0±1.3)d,(6.6±1.1)d],operative time[61(42,89)min,82(62,105)min,115(96,142)min],enucleation efficiency[1.29(0.71,1.56)g/min,1.67(1.23,2.15)g/min,2.74(2.20,3.34)g/min],and hemoglobin drop values[12(7,19)g/L,17(11,24)g/L,27(19,35)g/L]were statistically different(P＜0.05).Linear regression ana-lysis was used to show a strong positive linear correlation between enucleation efficiency and enucleation weight(r=0.880,P＜0.001),and the enucleation efficiency increased with the increase of prostate volume.The differences in IPSS[(6.6±1.7),(6.2±1.4),(4.6±1.1)]and Qmax[(18.9±3.1)mL/s,(16.8±3.8)mL/s,(22.9±7.1)mL/s]were not statistically significant among the three groups(P＞0.05),and the differences in IPSS and Qmax were statistically significant compared with those before surgery.The differences were statistically significant in preoperative comparisons,but the postoperative urinary flow rate of group C increased significantly more than the remaining two groups in terms of Qmax(P＜0.05).The patients in the three groups were followed up for 3 months,and post-operative complications were categorized into Clavien-Dindo Ⅰ(urinary retention,persistent hematu-ria),Clavien-Dindo Ⅱ(glandular remnants,urinary tract infection,blood transfusion)and Clavien-Dindo Ⅲ(urethral stenosis,contracture of the bladder neck,and reoperation for hemorrhage)based on the Clavien-Dindo Complications System score,the incidence of Clavien-Dindo in the three groups was 5.2％(13 cases),6.7％(12 cases)and 12.1％(7 cases),respectively,with statistically significant differences(P＜0.05);among them,there were statistically significant differences in urinary infection,blood transfusion and bleeding reoperation(P＜0.05),and there was no statistically significant difference in the remaining complications(P＞0.05).Conclusion:The risk of blood transfusion and re-hemostasis increases with larger prostate volume,the efficiency of enucleation increases with the increase of prostate vo-lume,and thulium fiber laser prostate enucleation is safe and effective in the treatment of large-volume BPH.