Objective To investigate the predictive value of the combined tumor burden score (TBS) and platelet-albumin-bilirubin (PALBI) score model for postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma (HCC). Methods The general information of 158 recipients diagnosed with HCC and underwent liver transplantation at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from 2008 to 2021 was collected. Lasso regression analysis combined with multivariate Cox regression analysis were used to identify independent risk factors for postoperative tumor recurrence after liver transplantation with HCC. A nomogram prediction model was constructed based on variables selected by Lasso regression analysis, and the predictive performance of the model was verified by calibration curve and clinical decision curve. The optimal cut-off values for postoperative tumor recurrence in liver transplant recipients with HCC were determined by receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis was used to compare survival differences among different groups. Results Among the 158 liver transplant recipients with HCC, 82 experienced tumor recurrence, with a recurrence rate of 51.9% and a median tumor-free survival time of 10 (4, 25) months. Results of Lasso regression analysis and multivariate Cox regression analysis showed that alpha-fetoprotein (AFP) ≥400 ng/mL, TBS and PALBI score were all independent risk factors for postoperative tumor recurrence in liver transplant recipients with HCC (all P<0.05). The combined high TBS-high PALBI score showed the highest predictive value (hazard ratio 6.909, 95% confidence interval 3.067-15.563, P<0.001). A nomogram prediction model was constructed based on six variables selected by Lasso regression analysis. Calibration curve showed good consistency between the model's predicted results and the ideal curve. Decision curve analysis indicated that the nomogram prediction model provided the highest clinical benefit for predicting 1-year tumor-free survival after liver transplantation with HCC. Time-dependent ROC curves at 1, 3 and 5 years after surgery showed that TBS-PALBI model had good predictive performance, with no significant difference in area under the curve (AUC) compared with TBS-PALBI-AFP model. The optimal cut-off values for predicting postoperative tumor recurrence were determined by ROC curve, with a PALBI score cut-off of −2.334 and a TBS cut-off of 5.305. Recipients were divided into a low TBS-low PALBI score group (n=47) and a low/high TBS-low/high PALBI score group (at least one score was high) (n=111). Kaplan-Meier survival analysis showed that the low TBS-low PALBI score group had a higher tumor-free survival rate than the low/high TBS-low/high PALBI score group, with a significant difference (P<0.05). Conclusions TBS-PALBI model provides a novel, simple and effective tool for assessing the prognosis of liver transplant recipients with HCC. The nomogram model constructed based on this has significant advantages in predictive performance and may serve as a reference for guiding individualized treatment plans and improving clinical outcomes.

AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.

In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide in vivo process is a key scientific problem that needs to be solved for polysaccharide drug development. Some progress has been made in the field of polysaccharide pharmacokinetics and immunomodulation. However, due to the lack of both chromogenic and light-absorbing groups and the complex molecular structure of polysaccharides, the in vivo processes and immunomodulatory mechanisms of polysaccharides have been slow to be investigated. The effective combination of multiple techniques can break the bottleneck of difficult tracing and unknown immunomodulatory mechanism of polysaccharides in vivo, and promote the development and utilization of polysaccharides. In this paper, we systematically summarize the key techniques in the study of polysaccharide in vivo processes and immunomodulatory mechanisms in order to provide technical references and research ideas for the study of polysaccharide in vivo processes and immunomodulatory mechanisms.

Objective To observe the regulatory mechanism of drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method on the expression of growth and differentiation factor 9(GDF9)and apoptosis of ovarian granulosa cells in rats with controlled ovarian hyperstimulation(COH).Methods Serum of COH rats(blank serum)and serum of COH rats gavaged by the Jinghou Zengzhi Prescription were prepared.A COH rat model was established and ovarian granulosa cells were collected.The experiment was divided into 5 groups:blank serum group,drug-containing serum group,drug-containing serum+SB203580[p38 mitogen-activated protein kinase(p38MAPK)inhibitor]group,drug-containing serum + PDTC[nuclear transcription factor κB(NF-κB)inhibitor]group,drug-containing serum + SB203580 + PDTC group.The mRNA expression levels of p38MAPK,casein kinase 2(CK2),nuclear transcription factor κB inhibitor α(IκBα),NF-κB and GDF9 were detected by real-time quantitative polymerase chain reaction(qRT-PCR),and GDF9 protein expression level was detected by Western Blot,and ovarian granulosa cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).Results The drug-containing serum of Jinghou Zengzhi Prescription decreased the mRNA expressions of p38MAPK and NF-κB,elevated the mRNA expressions of CK2 and IκBα,increased the mRNA and protein expression levels of GDF9,and decreased the apoptosis rate of ovarian granulosa cells in COH rats.The addition of p38MAPK inhibitor SB203580 alone and the addition of NF-κB inhibitor PDTC alone both promoted the mRNA and protein expressions of GDF9 and reduced the apoptosis rate of granulosa cells.Conclusion The drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method can promote the expression of GDF9 and inhibit the apoptosis of ovarian granulosa cells in rats with COH,and its mechanism may be related to the regulation of the expression of genes of the dual signaling pathways of p38MAPK and NF-κB.

BACKGROUND:Clinical treatment for colon cancer mainly includes fluorouracil,irinotecan and oxaliplatin-based therapy.Studies have shown that membrane transport proteins such as ATP-binding cassette transport protein of G2(ABCG2)mediate the transport of these drugs.However,when patients develop resistance to these chemotherapeutic drugs,the high expression of ABCG2 leads to a significant decrease in the therapeutic effect and raises the problem of drug resistance in colon cancer.New drugs and treatments are urgently needed to improve the efficacy.Lycium barbarum polysaccharide has a wide range of biological activities.It can be used as anti-tumor drug to overcome the damage to normal cells in the process of chemotherapy and radiotherapy in tumor patients. OBJECTIVE:To explore the reversal effect of Lycium barbarum polysaccharide in combination with oxaliplatin on colon cancer drug-resistant cells through in vitro experiments to investigate the possible molecular mechanism of Lycium barbarum polysaccharide reversal on colon cancer drug-resistant cells. METHODS:Colon cancer cell line HCT116 and oxaliplatin-resistant cell line HCT116-OXR were selected for in vitro experiments.The optimal intervention concentration and intervention time of Lycium barbarum polysaccharide and oxaliplatin were determined by CCK8 assay of cell proliferation.Samples were further divided into the HCT116 control group,HCT116-OXR blank treatment group,Lycium barbarum polysaccharide group(2.5 mg/mL Lycium barbarum polysaccharide),and oxaliplatin group(10 μmol/L oxaliplatin),and Lycium barbarum polysaccharide + oxaliplatin group(2.5 mg/mL Lycium barbarum polysaccharide +10 μmol/L oxaliplatin).Cell apoptosis was detected by flow cytometry.The protein expression levels of phosphomannose isomerase(PMI)and ABCG2 were detected by immunofluorescence and western blot assay.Phosphatidylinositol3-kinase(PI3K),protein kinase B(AKT),B-cell lymphoma 2(Bcl-2)and BCL2-Associated X(Bax)were detected by western blot assay. RESULTS AND CONCLUSION:(1)HCT116-OXR was more sensitive to Lycium barbarum polysaccharide compared to HCT116(P<0.05).(2)Compared with the HCT116-OXR blank group,Lycium barbarum polysaccharide + oxaliplatin could promote apoptosis of HCT116-OXR cells(P<0.05).The protein expression of Bcl-2 was significantly down-regulated(P<0.05);the protein expression of Bax was significantly up-regulated(P<0.05);the protein expression of ABCG2,PMI,PI3K and AKT was significantly down-regulated(P<0.05).(3)These results indicate that Lycium barbarum polysaccharide reverses drug resistance in colon cancer by inhibiting PMI/PI3K/AKT signaling pathway,which lays the foundation for studying the molecular mechanism of Lycium barbarum polysaccharide's sensitizing chemotherapeutic effects.

OBJECTIVE To investigate the effect of pachymic acid （PA） on renal function and fibrosis in chronic renal failure （CRF） rats and its potential mechanism based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. METHODS Using male SD rats as subjects， the CRF model was established by 5/6 nephrectomy； the successfully modeled rats were divided into model group， PA low-dose， medium-dose and high-dose groups （5， 10， 20 mg/kg PA）， high-dose PA+ROCK pathway activator lysophosphatidic acid （LPA） group （20 mg/kg PA+1 mg/kg LPA）， with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein， once a day， for 12 consecutive weeks. During the experiment， the general condition of rats was observed in each group. After the last administration， the serum renal function indexes （blood urea nitrogen， serum creatinine， uric acid） of rats in each group were detected， the renal histopathological changes were observed； the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] and inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6）， the positive expression rates of connective tissue growth factor （CTGF） and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins （RhoA， ROCK1） and fibrosis- related proteins （transforming growth factor-β1， bare corneum homologs 2， α-smooth muscle actin） were determined. RESULTS Compared with the sham operation group， the rats in model group had reduced diet， smaller body size， listless spirit and sluggish response， reduced and atrophied glomeruli， dilated renal tubules with chaotic structure， and a large number of inflammatory cells infiltrated interstitium； the serum levels of renal function indexes， renal tubule injury score， renal fibrosis area proportion， the levels of MDA and inflammatory factors， the positive expression rates of CTGF and collagen Ⅰ， and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased， while SOD level was significantly decreased （P＜0.05）. Compared with the model group， the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees，and the above quantitative indexes were significantly improved in a dose-dependent manner （P＜0.05）. LPA could significantly reverse the improvement effect of PA on the above indicators （P＜0.05）. CONCLUSIONS PA can improve renal function and alleviate renal fibrosis in CRF rats， which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.

Objective To investigate the potential mechanism of ibandronate sodium(IB)in alleviating inflammatory damage in diabetic osteoporosis rats by activating the nuclear transcription factor erythro 2-associated factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods Intraperitoneal injection of streptozotocin at several low doess was used to induce rat model of diabetes mellitus,then bilateral oophorectomy were used to establish type 2 diabetic osteoporosis(T2DOP)rat model.T2DOP model rats were divided into model group,control group,combined group and experimental-L,-M,-H groups,with 8 rats in each group;another 8 diabetic rats were selected as blank group.Model group was treated with normal saline.Control group was given the same volume of solvent.Experimental-L,-M,-H groups were given 2,10 and 50 mg·kg-1 IB.Combined group was treated with 50 mg·kg-1 IB and 50 mg·kg-1 ML385.Seven groups were administered intraperitoneally once a day for 12 weeks.After 12 weeks of treatment,the bone morphologic parameters were detected by calxanthoprotein double labeling method,the expression levels of Nrf2 and HO-1 pathway protein were detected by Western blot.Results The bone morphologic parameters of experimental-M,-H groups,combined group,control group,model group and blank group were 1.74±0.32,2.94±0.58,0.98±0.32,1.01±0.24,0.98±0.42 and 2.92±0.42;the relative expression levels of Nrf2 protein were 0.99±0.09,1.47±0.12,0.51±0.06,0.52±0.06,0.52±0.05 and 1.48±0.12;the relative expression levels of HO-1 protein were 1.02±0.11,1.33±0.14,0.61±0.05,0.59±0.06,0.62±0.06 and 1.29±0.13,respectively.The above indexes in the control group were statistically different with those in the experimental-M,-H groups(all P＜0.05).Conclusion IB repairs bone microstructure and alleviates inflammation in diabetic osteoporosis rats by activating the Nrf2/HO-1 signaling pathway.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.