Promise and challenges of traditional Chinese medicine,specifically Calculus bovis,in liver cancer treatment

Liver cancer,one of the most common malignancies worldwide,ranks sixth in incidence and third in mortality.Liver cancer treatment options are diverse,inclu-ding surgical resection,liver transplantation,percutaneous ablation,transarterial chemoembolization,radiotherapy,chemotherapy,targeted therapy,immuno-therapy,and traditional Chinese medicine(TCM).A multidisciplinary team(MDT)is essential to customize treatment plans based on tumor staging,liver function,and performance status(PS),ensuring individualized patient care.Treatment decisions require a MDT to tailor strategies based on tumor staging,liver function,and PS,ensuring personalized care.The approval of new first-line and second-line drugs and the establishment of standard treatments based on immune checkpoint inhibitors have significantly expanded treatment options for advanced liver cancer,improving overall prognosis.However,many patients do not respond effectively to these treatments and ultimately succumb to the disease.Modern oncology treatments,while extending patient survival,often come with severe side effects,resistance,and damage to the body,negatively impacting quality of life.Huang et al's study published at World Journal of Gastroenterology rigorously validates the anticancer properties of Calculus bovis,enhancing our understanding of TCM and contributing to new liver cancer treatment strategies.For over 5000 years,TCM has been used in East Asian countries like China to treat various diseases,including liver conditions.Analysis of real-world clinical data suggests that for patients with advanced-stage tumors lacking effective treatments,integrated TCM therapies could provide significant breakthroughs.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Relationship between dietary fiber intake and chronic diarrhea in adults

BACKGROUND Dietary fiber is essential for human health and can help reduce the symptoms of constipation.However,the relationship between dietary fiber and diarrhea is,poorly understood.AIM To evaluate the relationship between dietary fiber and chronic diarrhea.METHODS This retrospective study was conducted using data from the United States National Health and Nutrition Examination Survey,conducted between 2005 and 2010.Participants over the age of 20 were included.To measure dietary fiber consumption,two 24-hour meal recall interviews were conducted.The independent relationship between the total amount of dietary fiber and chronic diarrhea was evaluated with multiple logistic regression and interaction analysis.RESULTS Data from 12829 participants were analyzed.Participants without chronic diarrhea consumed more dietary fiber than participants with chronic diarrhea(29.7 vs 28.5,P=0.004).Additionally,in participants with chronic diarrhea,a correlation between sex and dietary fiber intake was present:Women who consume more than 25 g of dietary fiber daily can reduce the occurrence of chronic diarrhea.CONCLUSION Dietary fiber can reduce the occurrence of chronic diarrhea.

H_2S Protecting against Lung Injury following Limb Ischemia-reperfusion by Alleviating Inflammation and Water Transport Abnormality in Rats

Objective To investigate the effect of H2S on lower limb ischemia-reperfusion （LIR） induced lung injury and explore the underlying mechanism. Methods Wistar rats were randomly divided into control group, IR group, IR＋ Sodium Hydrosulphide （NariS） group and IR＋ DL-propargylglycine （PPG） group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NariS （0.78 mg/kg） as exogenous H2S donor and PPG （60 mg/kg） which can suppress endogenous H2S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 （AQP1）, aquaporin-5 （AQP5） as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 （TLR4）, myeloid differentiation primary-response gene 88 （MyD88） and p-NF-KB as indexes of inflammation. Results LIR induced lung injury was accompanied with upregulation of TLR4-Myd88-NF-κB pathway and downregulation of AQP1/AQP5. NariS pre-treatment reduced lung injury with increasing AQP1/AQP5 expression and inhibition of TLR4-Myd88-NF-KB pathway, but PPG adjusted AO.PJAO.Ps and TLR4 pathway to the opposite side and exacerbated lung injury. Conclusion Endogenous H2S, TLR4-Myd88-NF-κB pathway and AQP1/AQP5 were involved in LIR induced lung injury. Increased H2S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR4-Myd88-NF-κB pathway and AQP1/AQP5 expression to reduce inflammatory reaction and lessen pulmonary edema.

The theory of critical flicker fusion frequency and its application in cataracts

Background:Due to media opacity,it is usually difficult to accurately evaluate the postoperative visual acuity in cataracts patients.As a small and portable tool,the critical flicker fusion frequency(CFF)device reflects the temporal resolution of visual function and has been widely used in clinical research.However,poor understanding of the technique and equipment limitations have restricted its clinical application in China.Main text:There was a decrease in the CFF value in various ophthalmic diseases,indicating that the CFF is sensitive to detect visual functional changes.A number of studies have shown that the CFF test can accurately distinguish patients with simple cataracts from those with cataracts combined with fundus disease,and,as a visual test,it can more accurately predict postoperative visual acuity without being affected by media opacity.This study comprehensive reviews the basic principles of CFF and its application in ophthalmology,especially in cataracts.Conclusions:As one of the tools for dynamic visual function detection,the CFF test could help doctors to assess the possible presence of fundus disease in cataracts patients,especially in eyes with dense cataracts,and more precisely provide a reasonable visual prognosis than other available visual tests.

Dynesys dynamic stabilization system for the lumbar degenerative disease： a preliminary report from China

Background Dynesys dynamic stabilization system in 2007. Therefore, it was a new technique for Ch about Dynesys in China. The objective of this study degenerative disease in China. was first implanted in patients in 1994, and introduced to China nese orthopedics and hence necessary to collect clinical data was to report the preliminary results of Dynesys for the lumbar Methods Twenty-seven patients were treated with the Dynesys between July 2007 and January 2009. The diagnosis included degenerative spondylolisthesis （12 cases）, degenerative spinal stenosis （nine cases）, and lumbar intervertebral disc herniation （six cases）. Back pain and leg pain were evaluated using 100-mm visual analog scales （VAS）. The Oswestry Disability Index （ODI） was used to evaluate the patients＇ function. The intervertebral disc height and range of motion at the operative level were taken on radiographs. Results All the patients were followed-up, with an average of （22.40±4.23） months （range 15±32 months）. VAS of back pain and leg pain were improved significantly （P 〈0.05） at foUow-up. The ODI scores were reduced from （62.58±12.01）% preoperatively to （15.01±5.71）% at follow-up （P 〈0.05）. The preoperative mean height of the intervertebral disc was （11.21±1.58） mm （range 8.5±13.8 mm） and mean was （10.10±1.78） mm （range 7.0±13.4 mm） at follow-up （P 〈0.05）. The mean range of motion of the implanted segment was （6.00±1.79）° （range 2.5-9.3°） preoperatively and （5.47±1.27）° （range 2.9±7.8°） at follow-up （P=0.11）. Conclusions The preliminary results of Dynesys for the lumbar degenerative disease in China are similar to the published results of other countries. It can significantly improve the clinic symptoms and preserved motion at the level of implantation. However, the long-term follow-up data need to be collected.

Transforming Growth Factor-beta I Involved in the Pathogenesis of Endometriosis through Regulating Expression of Vascular Endothelial Growth Factor under Hypoxia

Background： Endometriosis （EMs） is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance ofectopic endometriotic lesions. Transtbrming growth factor-beta I （TGF-β1） plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions. Methods： Endometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA （mRNA） and protein expression levels ofTGF-β1, vascular endothelial growth fhctor （VEGF）, and hypoxia-inducible fhctor-Ic~ （HIF-β1） were measured. A DuaI-Luciferase Reporter Assay was used to examine the effect ofTGF-[31 and hypoxia on a VEGF promoter construct. Student＇s t-test was pertbrmed/br comparison among groups （one-sided or two-sided） and a value ofP 〈 0.05 was considered statistically significant. Results： TGF-β1, VEGF, HIF-β1 mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue （t = 2.16, P = 0.042）. EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein （t = 6.84, P - 0.023）. VEGF mRNA levels increased 12.5% in response to TGF-β1, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production （87.5% increases） of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 （2.6-fold, t = 6.08, P = 0.032） or hypoxia （11.2-fold, t = 32.70, P 〈 0.001 ）, whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect （ 18.5-fold, t = 33.50, P 〈 0.001 ）. Conclusions： The data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-[31 and hypoxia is taking place at the transcriptional level.

Expression and Prognostic Value of Indoleamine 2,3-dioxygenase in Pancreatic Cancer

Background： Indoleamine 2,3-dioxygenase （IDO）, an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. Methods： We evaluated the protein expression of IDO in PANC-1, CFPAC-I, and BxPC-3 cell lines with or without 48 11 treatment by 500 U/ml interferon-,/（IFN-y）. We performed immunollistochemical staining and Western blot analysis lbr IDO expression in both pancreatic cancer and normal pancreas tissues obtained from Chinese PLA General Hospital from July 2012 to December 2013. Survival analysis was performed to correlate IDO expression and histopathologic parameters with overall survival. The Kaplan-Meier method and Cox proportional hazards regression model were conducted. Results＂ PANC-I, CFPAC-I, and BxPC-3 cell lines expressed IDO at the protein level, and the relative expression amount increased after stimulation with 500 U/ml IFN-y. Immunohistochemical analysis results revealed that high IDO expression was observed in 59% of pancreatic adenocarcinoma tissues. Compared with normal pancreatic tissues, pancreatic adenocarcinoma showed significantly higher IDO expression levels, especially among patients with high tumor node metastasis （TNM） stages （X2= 4.550, P = 0.030）, poor histological differentiation （X2=5.690, P = 0.017）, and lymph node metastasis （X2=4.340 P = 0.037）. Kaplan-Meier survival curves showed that high 1DO expression was correlated with low survival rates （hazard ratio [HR] = 0.49 P = 0.009）. Multivariate analysis using Cox proportional hazards model indicated that lymph node metastasis （HR = 0.35 P= 0.010） and IDO expression （HR = 0.42 P = 0.020） were two independent prognostic predictors of pancreatic adenocarcinoma. Conclusions： The study confirmed that high IDO expression in pancreatic adenocarcinoma was related to poor prognosis of patients. These findings provided evidence that IDO was involved in pancreatic adenocarcinoma progression and might serve as a relevant therapeutic target.

Individualized Immunosuppressive Protocol of Liver Transplant Recipient Should be Made Based on Splenic Function Status

Background： Lymphocyte subsets play important roles in rejection in liver transplant recipients, and the effect of splenic function on these roles remains unknown. The aim of this study was to explore the feasibility to adjust immunosuppressive agents based on splenic function status through detecting the lymphocyte subsets in liver transplant recipients. Methods： The lymphocyte subsets of 49 liver transplant recipients were assessed in the 309th Hospital of Chinese People＇s Liberation Army between June 2014 and August 2015. The patients were divided into splenectomy group （n - 9）, normal splenic function group （n = 24）, and hypersplenism group （n = 16）. The percentages and counts of CD4＋ T, CD8＋ T, natural killer （NK） cell, B-cell, regulatory B-cell （Breg）, and regulatory T-cell （Treg） were detected by flow cytometer. In addition, the immunosuppressive agents, histories of rejection and infection, and postoperative time of the patients were compared among the three groups. Results： There was no significant difference of clinical characteristics among the three groups. The percentage ofCD 19＋CD24＋CD38＋ Breg was significantly higher in hypersplenism group than normal splenic function group and splenectomy group （3.29±0.97% vs. 2.12 i 1.08% and 1.90 ± 0.99%, P = 0.001）. The same result was found in CD4＋CD25＋FoxP3＋ Treg percentage （0.97 ± 0.39% vs. 0.54 ±0.31% and 0.56 ± 0.28%, P = 0.001 ）. The counts of CD8＋ T-cell, CD4＋ T-cell, and NK cell were significantly lower in hypersplenism group than normal splenic function group （254.25 ± 149.08 vs. 476.96 ± 225.52, P = 0.002; 301.69 ±154.39 vs. 532.50 ±194.42, P= 0.000; and 88.56± 63.15 vs. 188.33± 134.51, P = 0.048）. Moreover, the counts of CD4＋ T-cell and NK cell were significantly lower in hypersplenism group than splenectomy group （301.69 ± 154.39 vs. 491.89 ± 132.31, P = 0.033; and 88.56 ± 63.15 vs. 226.00± 168.85, P 0.032）. Conclusion： Splenic function status might affect the immunity of liver transplant recipients, that should be considered when we make immunosuppressive protocols.

Factors influencing outcomes of intra-aortic balloon counterpulsation in elderly patients

Background Intra-aortic balloon counterpulsation （IABP） is a mechanical cardiac-assist device that is used for cardiac support. There are no published reports about the use of IABP in elderly Chinese patients, especially for those over 80 years old. The aim of this study was to describe the clinical outcomes, influencing factors, and complications in patients 〉80 years old and requiring IABP. Methods We performed a retrospective study of 134 consecutive patients who received IABP therapy. Based on age, we defined two groups; those 〉80 years old and those 〈80 years old. Results The overall mortality was 41.8%. Patients -〉80 years old had higher mortality rates than those 〈80 years old （47.9% vs. 30.2%）. Patients 〉80 years old had fewer successful revascularizations （45.8%） and more pulmonary infections （47.9%） than patients 〈80 years old （60.3% and 30.2%, respectively）; these differences were statistically significant. The most common non-cardiac complication was pulmonary infection. Cardiogenic shock and pulmonary infection were risk factors for all-cause, in-hospital mortality, whereas revascularization success was a negative risk factor for the -〉80 years old patients. Conclusions IABP may be successfully and safely employed in patients 〉80 years old, having severe heart disease, with few complications. Patients 〉80 years old who need IABP therapy are less likely to have a successful revascularization and are more likely to develop pulmonary infections than patients 〈80 years old.

Treatment of Epilepsy with Bipolar Electro-coagulation： An Analysis of Cortical Blood Flow and Histological Change in Temporal Lobe

Background：Bipolar electro-coagulation has a reported efficacy in treating epilepsy involving functional cortex by pure electro-coagulation or combination with resection.However,the mechanisms of bipolar electro-coagulation are not completely known.We studied the acute cortical blood flow and histological changes after bipolar electro-coagulation in 24 patients with intractable temporal lobe epilepsy.Methods：Twenty-four patients were consecutively enrolled,and divided into three groups according to the date of admission.The regional cortical blood flow （rCBF）,electrocorticography,the depth of cortex damage,and acute histological changes （H and E staining,neuronal staining and neurofilament （NF） staining） were analyzed before and after the operation.The t-test analysis was used to compare the rCBF before and after the operation.Results：The rCBF after coagulation was significantly reduced （P 〈 0.05）.The spikes were significantly reduced after electro-coagulation.For the temporal cortex,the depth of cortical damage with output power of 2-9 W after electro-coagulation was 0.34 ± 0.03,0.48 ± 0.06,0.69 ± 0.06,0.84 ± 0.09,0.98 ± 0.08,1.10 ± 0.1 l,1.11 ± 0.09,and 1.22 ± 0.11 mm,respectively.Coagulation with output power of 4-5 W completely damaged the neurons and NF protein in the molecular layer,external granular layer,and external pyramidal layer.Conclusions：The electro-coagulation not only destroyed the neurons and NF protein,but also reduced the rCBF.We concluded that the injuries caused by electro-coagulation would prevent horizontal synchronization and spread of epileptic discharges,and partially destroy the epileptic focus.

Programmed death 1 mRNA in peripheral blood as biomarker of acute renal allograft rejection

Background Invasive kidney biopsy is a priority diagnostic method for the acute rejection after renal transplantation for the past decades. However, no effective and noninvasive assay for predicting the severity of acute rejection is in wide use at present. This study was designed to investigate the predictive value of programmed death 1 （PD-1） mRNA for acute rejection after renal transplantation with real-time reverse transcriptase polymerase chain reaction （RT-PCR）. A noninvasive diagnostic method has been expected to replace the tranditional kidney biopsy for the diagnosis of acute rejection and prediction of the outcome after kidney transplantation.Methods The whole blood samples from 19 subjects with acute rejection, 20 subjects with delayed graft function （DGF） and 21 subjects with stable recipients after kidney transplantation in a single kidney transplantation center between 2006 and 2009 were collected. The messenger RNA （mRNA） of PD-1 was analyzed with real-time RT-PCR. The associations of PD-1 mRNA levels with acute rejection and disease severity were investigated.Results The log-transformed ratio of PD-1 mRNA to GAPDH mRNA was higher in peripheral blood mononuclear cell （PBMC） from the group with acute rejection （4.52±1.1） than that from the group with DGF （1.12±0.6） or the group with normal biopsy results （0.7±0.4） （P 〈0.01, by the Kruskal-Wallis test）. PD-1 mRNA levels were correlated with serum creatinine levels measured at the time of biopsy in the acute rejection group （Spearman＇s correlation coefficient, r=0.81, P=0.03）, but not in the group with DGF or the group with normal biopsy results. PD-1 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection.Conclusions Our data suggest that PD-1 status may be a new predictor of acute rejection and the levels of PD-1 mRNA in whole blood cells may positively correlate with the severity of acute rejection after renal transplantation. Meanwhile, the data provide the rational for interfering into the PD-1/PD-L1 as a novel therapy against the acute rejection after renal transplantation in clinical settings.

A comparative study of alteration in retinal layer segmentation alteration by SD-OCT in neuromyelitis optica spectrum disorders: A systematic review and meta-analysis

Background:To evaluate the feature of different retinal layer segmentation in neuromyelitis optica spectrum disorders(NMOSD)with spectral-domain optical coherence tomography(SD-OCT)and to compare it with that in multiple sclerosis(MS),healthy controls(HC),and idiopathic optic neuritis(ION).Methods:We retrieved four electronic databases,including Pubmed,Embase,Cochrane Library,and Web of Science from inception to September 1st,2021.A meta-analysis was performed to compare different retinal layer segmentation thicknesses between patients with or without a history of optic neuritis(ON)in NMOSD and the control group,including patients with MS,HC,and ION.Results:Forty-two studies were included and the interval between the last ON onset and examination was greater than 3 months.Compared with that in HC eyes,the loss of retinal nerve fiber layer(RNFL)and macular ganglion cell and inner plexiform layer(GC-IPL)was serious in NMOSD eye especially after ON.Moreover,compared with that in ION eyes or MS-related-ON eyes,the injury to the peripapillary retinal nerve fiber layer(pRNFL)was severe in NMOSD-related-ON eyes.In addition,the correlation coefficient between pRNFL and prognostic visual acuity was 0.43.However,the one-arm study revealed the inner nuclear layer(INL)was thickened in NMOSDrelated-ON eyes compared with HC eyes.Conclusions:Inclusion of the RNFL and macular GC-IPL is recommended for monitoring disease progression and attention should be paid to changes in the INL.

The clinical application of critical flicker fusion frequency in demyelinating optic neuritis

Purpose:To investigate the application of critical flicker fusion frequency(CFF)in demyelinating optic neuritis(DON).Methods:A cross-sectional study.A total of 127 eyes in 69 DON patients and 63 eyes in 33 healthy control(HC)groups were included between January 2021 to September 2021 from Department of Ophthalmology,PLA General Hospital.Patients underwent best-corrected visual acuity(BCVA),visual field,optical coherence tomography(OCT),flash visual evoked potential(F-VEP),and CFF examinations.The affected eyes were divided into aquaporins 4(AQP4-),myelin oligodendrocyte glycoprotein(MOG-),and double negative DON according to serum antibody;mild,moderate,severe degree visual impairment according to BCVA
0.5,0.1-0.5,<0.1;and 4 groups:<1,1~<3,3~<6 and>6 months according to time interval from onset to CFF examination.One-way ANOVA was used to perform above subgroup analysis.The correlations between CFF and F-VEP peak time,peak value,BCVA and mean visual filed defect(MD)were analyzed in order via Pearson correlation analysis.Results:he trichromatic values of red,green,and yellow in DON affected eyes were 21.83±9.03,23.66±10.21,24.09±10.77 Hz,respectively,which was significantly reduced compared with the HC group(t=-14.82,-14.22,-14.00;P<0.001).The subgroup analysis showed no significant difference between different antibody subtypes(P=0.914<0.848<0.604),whereas,a significant decrease of CFF trichromatic value was found in severe visual acuity impairment group(P<0.001).There was a significant difference in CFF-trichromatic values at different time points(P<0.001),to be specific,CFF fluctuated under 20Hz within 3 months after onset and tended to be stable around 24-28Hz.Correlation analysis showed that the peak time of F-VEP(r=-0.486,-0.515,-0.526;P<0.001),BVCA(r=-0.640,-0.659,-0.642;P<0.001),were negatively correlated with CFF trichromatic values,MD and CFF were positively correlated(r=0.486,0.453,0.476;P=0.003,0.006,0.004).Conclusions:A significant decrease of CFF value was found in DON-affected eyes,and it has a good correlation with BCVA,MD and latency of F-VEP,and can better reflect the impairment of visual function.