Objective To investigate the clinical efficacy of Xiaqi Decoction(mainly composed of Poria,Pinelliae Rhizoma Praeparatum,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Armeniacae Semen Amarum,Citri Grandis Exocarpium,Paeoniae Radix Alba,Polygoni Multiflori Radix,and Moutan Cortex)on patients with stage Ⅲ-Ⅳ colorectal cancer accompanied by cancer-related fatigue(CRF)after chemotherapy.Methods Sixty patients with stage Ⅲ-Ⅳ colorectal cancer accompanied by CRF after chemotherapy who admitted to Guangdong Second Traditional Chinese Medicine Hospital from January 2023 to March 2024 were randomly divided into chemotherapy group and Xiaqi Decoction group according to the random number table method,with 30 patients in each group.The chemotherapy group was given chemotherapy regimen of Avastin+mFOLFOX6/FOLFIRI,and Xiaqi Decoction group was given Xiaqi Decoction orally on the basis of treatment for the chemotherapy group.Two weeks constituted a course of treatment,and two consecutive courses of treatment were performed.Before and after treatment,the two groups were observed in the changes of Revised Piper Fatigue Scale(PFS-R)scores,EORTC Quality of Life Questionnaire-Core 30(QLQ-C30)scores,Patient-Generated Subjective Global Assessment(PG-SGA)scores,Karnofsky Performance Status(KPS)scores,poor appetite scores,and serum levels of interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and interleukin 1β(IL-1β)were observed.After treatment,the clinical efficacy and safety between the two groups of patients were evaluated.Results(1)After two courses of treatment,the total effective rate of the Xiaqi Decoction group was 86.21%(25/29)and that of the chemotherapy group was 62.07%(18/29),and the intergroup comparison(tested by chi-square test)showed that the efficacy of Xiaqi Decoction group was significantly superior to that of chemotherapy group(P<0.05).(2)In the second and fourth weeks of chemotherapy,the PFS-R scores for evaluating the degree of fatigue of patients in the two groups were increased when compared with those in the day before chemotherapy(P<0.05),but the PFS-R scores in Xiaqi Decoction group were significantly lower than those in the chemotherapy group after chemotherapy(P<0.01).(3)In the second and fourth weeks of chemotherapy,the QLQ-C30 scores for evaluating the quality of life in the chemotherapy group was decreased when compared with that one day before chemotherapy(P<0.05),whereas the QLQ-C30 scores in the Xiaqi Decoction group showed no obvious changes when compared with that one day before chemotherapy(P>0.05).The intergroup comparison showed that the QLQ-C30 scores of the Xiaqi Decoction group were all significantly higher than those of the chemotherapy group after chemotherapy(P<0.01).(4)The evaluation of nutritional status showed that in the fourth week of chemotherapy,PG-SGA score and poor appetite score in the two groups as well as KPS score in Xiaqi Decoction group were increased when compared with those one day before chemotherapy(P<0.05),while the KPS score in the chemotherapy group was decreased when compared with that one day before chemotherapy(P<0.05).The intergroup comparison showed that PG-SGA score and poor appetite score of Xiaqi Decoction after chemotherapy were lower than those of the chemotherapy group,and the KPS score was higher than that of the chemotherapy group,the differences being statistically significant(P<0.05 or P<0.01).(5)In the chemotherapy group,the serum inflammatory factor levels of TNF-α and IL-6 in the second week of chemotherapy and the serum TNF-α,IL-1β and IL-6 levels in the fourth week of chemotherapy were all increased when compared with those one day before chemotherapy(P<0.05).In the Xiaqi Decoction group,the serum TNF-α,IL-1β,and IL-6 levels were all decreased when compared with those one day before chemotherapy,and significant differences were shown in the serum IL-6 level in the second week of chemotherapy and in the serum levels of IL-1β and IL-6 in the fourth week of chemotherapy when compared with those one day before chemotherapy(P<0.05).The intergroup comparison showed that serum TNF-α,IL-1β,and IL-6 levels in the Xiaqi Decoction group after chemotherapy were significantly lower than those in the chemotherapy group(P<0.05 or P<0.01).Conclusion Xiaqi Decoction is effective on relieving the clinical symptoms and enhancing the efficacy of patients receiving chemotherapy for stage Ⅲ-Ⅳ colorectal cancer.It can inhibit the expression of inflammatory factors,relieve the CRF and improve the nutritional status and the quality of life of the patients,with higher safety.

Objective To observe the therapeutic effect and mechanism of Xiaqi Decoction for mice with chemotherapy-induced cancer-related fatigue(CRF)in colon cancer.Methods The successfully constructed chemotherapy-induced CRF mouse model of colon cancer was randomly divided into the model control group and the Xiaqi Decoction group,with 10 mice in each group,and a blank control group was also set up.After each group was given the corresponding intervention,the mice exhaustive swimming time was determined,the tumor size was measured,the tumor inhibition rate was calculated,and the serum levels of inflammatory factors such as tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6 and other safety indicators such as alanine aminotransferase(ALT),aspartate aminotransferase(AST)and blood ureanitrogen(BUN)were detected by enzyme-linked immunosorbent assay(ELISA),the protein expression levels of Toll-like receptor 4(TLR4)and nuclear factor κB(NF-κB)p65 in the epithelial cells of tumor lumps(or axillary tissues)were detected by Western Blot.Results(1)Before treatment,the exhaustive swimming time of mice in the model control group was significantly less than that of the blank control group(P<0.01);after 28 days of treatment,the exhaustive swimming time of mice in the Xiaqi Decoction group was significantly longer than that of the model control group(P<0.01),and it was time-dependent.(2)The tumor size of mice in the Xiaqi Decoction group was gradually decreased from 4-28 days of treatment,and the tumor inhibition rate was 68.96%after 28 days of treatment.(3)The serum levels of TNF-α,IL-1β and IL-6 in the model control group were significantly higher than those in the blank control group(P<0.01);and the serum levels of TNF-α,IL-1β and IL-6 in the Xiaqi Decoction group were significantly lower than those in the model control group(P<0.05).(4)The serum levels of ALT,AST and BUN in the model control group were higher than those in the blank control group(P<0.05 or P<0.01);the serum levels of ALT,AST and BUN in the Xiaqi Decoction group were lower than those in the model control group(P<0.05).(5)The protein expression levels of TLR4 and NF-κB p65 in tumor epithelial cells of the model control group were higher than those of the blank control group(P<0.01);the protein expression levels of TLR4 and NF-κB p65 in tumor epithelial cells of the Xiaqi Decoction group were lower than those of the model control group(P<0.01).Conclusion Xiaqi Decoction can effectively promote physical recovery,and inhibit tumor growth in mice with chemotherapy-induced CRF of colon cancer,and its mechanism may be related to the inhibition of TLR4 and NF-κB p65 expression,thus to reduce the inflammatory response,with certain degree of safety.

Objective To observe the application effect of the H2H model in rehabilitation nurs-ing for patients undergoing radical mastectomy.Methods A total of 294 patients who underwent rad-ical mastectomy were enrolled as study subjects and randomly divided into conventional group and H2H group using a simple randomization method(coin toss),with 147 patients in each group.The conventional group received routine nursing interventions,while the H2H group received nursing in-terventions based on the H2H model.At 1 week and 3 months post-intervention,shoulder joint func-tion[assessed using the Constant-Murley Shoulder Function Score(CMS)],nutritional indicators(serum albumin,hemoglobin)levels,self-management efficacy[assessed using the Self-care Self-ef-ficacy Scale(SUPPH)],and quality of life[assessed using the Functional Assessment of Cancer Therapy-Breast(FACT-B)]were observed and compared between the two groups.Results At 3 months post-intervention,the pain,daily living activities,range of motion,and muscle strength scores in the CMS were higher than those at 1 week post-intervention in both groups,with the H2H group showing higher scores than the conventional group,and the differences were statistically signifi-cant(P＜0.05).At 3 months post-intervention,the albumin and hemoglobin levels were lower than those at 1 week post-intervention in both groups,but the H2H group had higher levels than the con-ventional group,and the differences were statistically significant(P＜0.05).At 3 months post-inter-vention,the positive attitude,self-decision-making,and self-stress reduction scores in the SUPPH were higher than those at 1 week post-intervention in both groups,with the H2H group showing higher scores than the conventional group,and the differences were statistically significant(P＜0.05).At 3 months post-intervention,the scores for physical well-being,social/family well-being,emotional well-being,functional well-being,and the breast cancer-specific module in the FACT-B were higher than those at 1 week post-intervention in both groups,with the H2H group showing higher scores than the conventional group,and the differences were statistically significant(P＜0.05).Conclu-sion The application of the H2H model in rehabilitation nursing for patients after radical mastecto-my can promote the recovery of shoulder joint function,improve nutritional status,and enhance self-management efficacy and quality of life.

As a supplement to randomized controlled trials， observational studies can provide evidence for the effectiveness of traditional Chinese medicine （TCM） treatment measures. They can also study influencing factors of diseases， etiology， and prognosis. However， there is a confounding effect due to the lack of randomization， which seriously affects the causal inference between the study factors and the outcome， resulting in confounding bias. Therefore， identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory， confounding factors can be categorized into measured and unmeasured confounding factors. In addition， attention must be paid to identifying confounding factors and intermediate variables， as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors， measured confounding factors can be controlled by stratification， multifactor analysis， propensity scores， and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods， difference-in-difference methods， and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups， and confounding bias can be reduced. In addition， methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM， observational studies of TCM face unique challenges in identifying and controlling confounding factors， including the ever-changing TCM treatment measures received by patients， the often-overlooked confounding effects in the four diagnostic information of TCM， and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues， providing a methodological basis for conducting higher-quality TCM observational studies， so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.

Objective To compare the differences in lipid metabolism between platinum-resistant and platinum-sensitive ovarian cancer patients at stage Ⅲ-Ⅳ,to analyze the differential intestinal flora using 16S rRNA sequen-cing,and to explore the associations among intestinal flora,lipid metabolism characteristics and platinum resistance in ovarian cancer.Methods Patients diagnosed with ovarian cancer at stage Ⅲ-Ⅳ through surgical pathology were selected,including a platinum-resistant group(11 cases)and a platinum-sensitive group(11 cases).The differences in lipid metabolism between the two groups were compared.The differences in gut microbiota between the two groups were investigated using fecal 16S rRNA sequencing.The association among gut microbiota,lipid metabolism characteristics,and platinum resistance in ovarian cancer was analyzed.Results Significant differ-ences were observed in lipid metabolism-related indicators[total cholesterol(TC),high-density lipoprotein choles-terol(HDL-C),non-high-density lipoprotein cholesterol(n-HDL),low-density lipoprotein cholesterol(LDL-C),apolipoprotein(B)]between the two groups,with higher levels in the platinum-resistant group.The Shannon in-dex(P=0.008 3)and Simpson index(P=0.008 2)both showed higher diversity of gut microbiota in platinum-resistant ovarian cancer patients compared to the platinum-sensitive group.However,based on OTUs species clus-tering and relative abundance statistics,certain bacterial abundances differed significantly between the groups.Spe-cies such as Parabacteroides,Akkermansia,Blautia,Lachnoclostridium,Fusicatenibacter,and Megamonas had sig-nificantly higher abundances in the platinum-sensitive ovarian cancer group,and Akkermansia(a lipid metabolism-related bacterial group)was the most prevalent.Conclusion The platinum-resistant group of ovarian cancer ex-hibits significantly higher levels of lipid metabolism and gut microbiota diversity compared to the platinum-sensitive group.This suggests that the increase in lipid metabolism levels and fecal microbiota diversity may be associated with the development of platinum resistance.However,certain microbial taxa are reduced in abundance in the plat-inum-resistant group,such as the distinct Akkermansia genus(a lipid metabolism-related microbial community),which may serve as one of the factors inducing platinum-resistance in ovarian cancer.

Objective To investigate the expression levels of serum high-mobility group box 1(HMGB1),soluble CD163(sCD163),and prostaglandin E2(PGE2)in patients with hepatitis B virus-related chronic-on-acute liver failure(HBV-ACLF),and to evaluate the value of the three indicators used alone or in combination in predicting prognosis.Methods A total of 76 patients with HBV-ACLF who were hospitalized in Department of Infectious Diseases,The First Affiliated Hospital of Xinxiang Medical University,from July 1,2022 to September 30,2023 were enrolled,and according to the 28-day prognosis,they were divided into survival group with 48 patients and death group with 28 patients.General data were collected,Model for End-Stage Liver Disease(MELD)score was calculated,and ELISA was used to measure the serum levels of HMGB1,sCD163,and PGE2.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.The Spearman rank correlation test was used to analyze the correlation of HMGB1,sCD163,and PGE2 with MELD score;the receiver operating characteristic(ROC)curve was used to analyze the value of HMGB1,sCD163,and PGE2 used alone or in combination in predicting the prognosis of HBV-ACLF patients.Results There were significant differences between the two groups in total bilirubin,white blood cell count,the percentage of neutrophils,procalcitonin,serum amyloid A,interleukin-6,serum sodium,and serum creatinine(all P＜0.05).Compared with the survival group,the death group had significantly higher serum levels of HMGB1(Z=-2.997,P=0.003)and sCD163(Z=-2.972,P=0.003),a significantly higher MELD score(t=-6.997,P＜0.001),and a significantly lower serum level of PGE2(Z=-4.909,P＜0.001).The Spearman rank correlation test showed that HMGB1 and sCD163 were positively correlated with MELD score(r=0.431 and 0.319,both P＜0.05),while PGE2 was negatively correlated with MELD score(r=-0.412,P＜0.05).The ROC curve analysis showed that HMGB1,sCD163,and PGE2 used alone had an area under the ROC curve(AUC)of 0.717,0.716,and 0.856,respectively,while the combination of the three indicators had the highest predictive value,with an AUC of 0.930,a sensitivity of 0.778,and a specificity of 0.920.Conclusion Serum HMGB1,sCD163,and PGE2 used alone or in combination have a good reference value in predicting the prognosis of HBV-ACLF patients,and the combination of the three indicators has the highest predictive value,which holds promise for further observation and research.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Objective:To investigate the changes in total radioactivity in patient body with differentiated thyroid carcinoma (DTC) after 131I treatment and the factors influencing its metabolism. Methods:The clinical data from 218 patients after DTC treatment in the Department of Nuclear Medicine, the Second Affiliated Hospital of Air Force Medical University from September 2021 to April 2022 were retrospectively analyzed. Based on administrated 131I dose, 171 patients were divided into low-dose group (≤ 3.7 GBq) and 47 into high-dose group (>3.7 GBq) . A whole body dynamic radiation monitoring system was used to measure the in vivo residual activity of 131I 24, 48 and 72 h after 131I administration and to explore their influencing factors. Results:24, 48 and 72 h after adimination of 131I, the residual activity of 131I in the low-dose group patients was significantly lower than in the high-dose group patients ( t= -7.46, -3.31, -2.01, P<0.05) . The discharge compliance rate at 24 and 48 h in the low-dose group was significantly higher than that in the high-dose group (21.0% vs. 4.3%, 98.2% vs. 89.4%, χ2 = 7.23, 5.91, P<0.05) , and all patients could meet the discharge criteria at 72 h. Univariate analysis showed that the residual 131I activity at 24 and 48 h was dependent on age, body mass index (BMI) , basal metabolism rate (BMR) and thyroid stimulating hormone (TSH) . As have been shown by multiple linear regression analysis, in the low-dose group, the older age, the higher BMR and the higher TSH level at 24 h tended to the higher 131I residual activity in the body. At 48 h, the higher BMI and the higher TSH level lead to the higher 131I residual activity in patient body. Meanwhile, in the high-dose group, the higher age and BMR at 24 h, tended to the higher in vivo131I residual activity. The influencing factors were analyzed in terms that 131I residual activity reaching 400 MBq in patient body at 24 and 36 h. The result showed that at 24 h the lower TSH level leaded to the lower 131I residual activity in patient body. At 36 h, the younger age, the lower TSH level, and the smaller 131I treatment dose tended to the lower in vivo131I residual activity. Conclusions:Age, BMI, BMR and TSH levels are the influencing factors for the change in total activity in patient body after 131I treatment of DTC. Radiation dose assessment based on the above indicators can provide a reference for adjusting the length of hospitalization time.

Objective:To investigate the characteristics of natural killer (NK) cell subsets and function in methicillin-resistant staphylococcus aureus (MRSA) sepsis, and to assess the influence of matrix metalloproteinase (MMP) to NK cell function in MRSA sepsis patients.Methods:Twenty-one MRSA sepsis patients who were hospitalized in our department between January 2017 and June 2018 were enrolled. Eleven healthy individuals were served as healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated. NK cell subsets were investigated by flow cytometry. NK cell function was assessed by measuring CD107a, CD69, and CD16 expression in co-culture system between PBMCs and different target cells. MMP mRNA was semi-quantified by real-time PCR in purified NK cells. The influence of NK cell function was assessed by measuring CD107a expression in co-culture system between NK cells with MMP inhibitor stimulation and target cells.Results:There was no significant difference of total NK cell percentage between healthy controls and MRSA sepsis patients ( P>0.05). CD56brightCD16 -NK [(5.36±1.02)% vs (4.30±0.89)%] and CD56 -CD16 +NK [(24.04±2.92)% vs (9.70±1.54)%] percentage was elevated ( P<0.05), while CD56dimCD16 +NK percentage [(71.22±13.03)% vs (87.64±7.05)%, P<0.01] was reduced in MRSA sepsis. NK cells recognized and killed target cells via different receptors upon activation. CD107a [(33.55±3.84)% vs (25.34±6.20)%] and CD69 percentage [(14.96±1.47)% vs(18.80±1.49)%] was decreased ( P<0.0001), while CD16 MFI was increased [(247.1±50.31) vs (189.4±57.54), P<0.01] in MRSA sepsis patients in comparison with healthy controls. MMP-1/2/3/9 mRNA relative levels were elevated in purified NK cells from MRSA sepsis patients ( P<0.01). Inhibition of MMP in NK cells from MRSA sepsis patients promoted CD107a percentage [(33.67±8.03)% vs (25.87±6.23)%, P=0.018]. Conclusions:NK cell subsets imbalance and exhaustion is existed in MRSA sepsis, which might be due to the MMP-induced down-regulation of antibody-dependent cell-mediated cytotoxicity.

Objective To investigate the expression of liver kinase B1 (LKB1) and phosphatase and tensin homology deleted on chromosome ten (PTEN) in hepatocellular carcinoma (HCC) and their relationship with pathological characteristics and prognosis of HCC.Methods hnmunohistochemistry was used to detect expression of LKB1 and PTEN in 115 HCC cases.The relationship between clinicopathologic factors and the expressions was analyzed.Results The positive expression rate of LKB1 and PTEN was 10.4％ (12/115) and 28.7％ (33/115) respectively.The coexpression ratio of LKB1 and PTEN was 5.2％ (6/115).LKB1 and PTEN double deletion rate was 66.1％,with the latter most often found in those ≥ 50 years of age group (x2 =7.968,P =0.001),middle low differentiation HCC group (x2 =11.297,P =0.025) and vascular tumor thrombus group (x2 =6.797,P =0.011).The 5 year survival rates of LKB1 and PTEN protein coexpression and double deletion patients were 100％ and 36.5％ (x2 =10.969,P =0.004),respectively.Multivariate COX regression analysis showed that vascular tumor thrombus,PTEN deletion and LKB1/PTEN double deletion were independent risk factors for the prognosis of HCC.Condusions Double deletion of LKB1/PTEN protein is one of the independent factors that affect the survival time of HCC patients.