Hepatocellular carcinoma （HCC） is a common malignant tumor with a high mortality rate， an insidious onset， and complex pathological mechanisms. In the tumor microenvironment， tumor-promoting immune cells protect tumor cells from immune attacks， while dysfunction of anti-tumor immune cells causes the inhibition of immune response， thereby leading to the continuous deterioration of cancer. In recent years， traditional Chinese medicine has shown good efficacy in the treatment of HCC， and it can inhibit the proliferation and metastasis of cancer cells by regulating immune cells. By analyzing related articles in China and globally， this article summarizes how immune cells affect the progression of HCC through the immunosuppressive pathway and how traditional Chinese medicine exerts an anti-HCC effect by regulating immune cells， in order to provide theoretical basis and reference for optimizing the treatment of HCC.

Hepatitis C is one of the main causes of liver cancer.With the application of direct-acting antiviral agents,more than 95%of patients can achieve the eradication of hepatitis C virus and obtain sustained virologic response(SVR).Effective antiviral therapy can change the natural course of hepatitis C and reduce the risk of liver cancer;however,some patients are still affected by age,sex,liver fibrosis,diabetes,hepatic steatosis,alcohol consumption,and genetic factors and become the high-risk population of liver cancer.Therefore,it is needed to further clarify and improve the identification and prediction of high-risk populations of liver cancer after SVR of hepatitis C.This article reviews the risk factors and predictive models for liver cancer after SVR in patients with hepatitis C,in order to provide a basis for identifying the high-risk population of liver cancer after SVR of hepatitis C in clinical practice.

Objective To evaluate the efficiency of fluorescent PCR melting curve method in early diag-nosis of fluoroquinolones (FQs) resistance in the patients with tuberculosis,and to analyze the situation and characteristics of FQs resistance,so as to provide a basis for the standardized diagnosis and treatment of rifam-picin resistance/multidrug resistant tuberculosis (RR/MDR-TB) and pre-extensively drug resistant tuberculo-sis (pre-XDR-TB).Methods A total of 1094 smear positive samples from the outpatients and inpatients of Guiyang Municipal Public Health Treatment Center from January 2021 to August 2022 were collected and conducted the Roche solid culture method and bacterial species identification.Finally,589 cases of tuberculosis conducted the phenotypic drug sensitivity test and fluorescent PCR melting curve method for detecting rifam-picin (RFP),isoniazid(INH),ethambutol(EMB) and FQs resistance.The phenotypic drug sensitivity test served as the standard to evaluated the diagnostic efficiency of the fluorescent PCR melting curve method;the relationship between the patients' FQs resistance and clinical characteristics was analyzed according to the phenotypic drug sensitivity results.Results The sensitivity,specificity,coincidence rate and Kappa value of fluorescence PCR melting curve method for detecting FQs drug resistance were 91.30％,97.69％,96.94％ and 0.86 respectively;the area under the curve (AUC) was 0.945,which was higher than 0.924,0.923 and 0.850 of RFP,INH and EMB.The drug resistance rate of FQs in the patients with RR/MDR-TB was 22.80％,the Kappa value of fluorescence PCR melting curve method for detecting the patients' FQs drug re-sistance was 0.83,the consistency was good,AUC was 0.936.There was no statistically significant difference in sensitivity,specificity and coincidence rate of FQs resistance in TB patients with different bacterial loads by fluorescence PCR fusion curve (P>0.05).The treatment type,history of anti-tuberculosis,pulmonary cavity and MDR-TB were related with FQs resistance (P<0.05).Conclusion The fluorescent PCR melting curve method has good diagnostic efficiency for FQs resistance in the patients with tuberculosis.

Objective:To investigate the effects of different doses of vitamin D diet early in life on airway inflammation in different endotypes of asthma mice models.Methods:In the Animal House of Shanghai General Hospital of Nanjing Medical University in June 2022, the BALB/c mice with 14 d pregnant were selected, the offspring mice were divided into vitamin D sufficient group and vitamin D deficient group by random number table method with 12 each. The mice in the vitamin D sufficient group were given a feed with sufficient vitamin D content, while the mice in the vitamin D deficient group were given a feed without vitamin D. At the age of 8 weeks, the mice were sensitized and stimulated with ovalbumin to establish a T2 type asthma model, while the mice were sensitized and stimulated with ovalbumin combined with ozone exposure to establish a non-T2 type asthma model, with 6 mice in each model. The level of serum 25 hydroxy vitamin D 3 was detected by enzyme-linked immunosorbent assay (ELISA) method. The lung tissue was stained with HE to evaluate the inflammatory response score and calculate the eosinophils density and neutrophils density. In bronchoalveolar lavage fluid (BALF), the expression levels of interleukin (IL)-4, IL-6, IL-10 and IL-17A, the inflammatory cell count (total cell count, neutrophil count and eosinophil count) were detected. Results:The 25 hydroxy vitamin D 3 in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly lower than that in vitamin D sufficient group: (8.12 ± 1.72) μg/L vs. (26.63 ± 2.54) μg/L and (6.86 ± 1.65) μg/L vs. (23.81 ± 3.09) μg/L, and there was statistical difference ( P<0.01). The inflammatory response score in non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in non-T2 type asthma mice of vitamin D sufficient group: (2.58 ± 0.49) scores vs. (1.83 ± 0.21) scores, and there was statistical difference ( P<0.05), there was no statistical differences in inflammatory response score in T2 type asthma mice between two groups ( P>0.05). The neutrophils density and eosinophils density in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly higher than those in vitamin D sufficient group, T2 type asthma mice: (20.30 ± 1.95) cells/100 μm vs. (12.58 ± 1.04) cells/100 μm and (5.25 ± 0.62) cells/100 μm vs. (3.15 ± 0.35) cells/100 μm; non-T2 type asthma mice: (53.48±5.19) cells/100 μm vs. (33.80 ± 2.74) cells/100 μm and (3.00 ± 0.29) cells/100 μm vs. (2.17 ± 0.21) cells/100 μm, and there were statistical differences ( P<0.01 or <0.05). The BALF total cell count in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in vitamin D sufficient group, the BALF eosinophil count in T2 type asthma mice of vitamin D deficient group was significantly higher than that in T2 type asthma mice of vitamin D sufficient group, the BALF neutrophil count in non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in T2 type asthma mice of vitamin D sufficient group, and there were statistical differences ( P<0.01); there was no statistical difference in BALF neutrophil count in T2 type asthma mice between two groups ( P>0.05); there was no statistical difference in BALF eosinophil count in non-T2 type asthma mice between two groups ( P>0.05). The BALF total cell count and neutrophil count in non-T2 type asthma mice of both groups were significantly higher than those in T2 type asthma mice, but the BALF eosinophil count in T2 type asthma mice was significantly higher non-T2 type asthma mice, and there were statistical differences ( P<0.05). The BALF IL-4, IL-6 and IL-17A in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly higher than those in vitamin D sufficient group, the BALF IL-10 was significantly lower than those in vitamin D sufficient group, and there were statistical differences ( P<0.01 or <0.05). In vitamin D deficient group, the BALF IL-4 in non-T2 type asthma mice was significantly lower than that in T2 type asthma mice, the BALF IL-6 and IL-17A were significantly higher than those in T2 type asthma mice, and there were statistical differences ( P<0.05); in vitamin D sufficient group, the BALF IL-6 and IL-17A in non-T2 type asthma mice were significantly higher than those in T2 type asthma mice, and there were statistical differences ( P<0.05). Conclusions:Vitamin D deficiency is involved in different mechanisms of airway inflammation in T2 type asthma and non-T2 type asthma, and this effect may be more obvious for non-T2 type asthma.

ObjectiveTo investigate whether cytotoxic T lymphocyte （CTL）－derived exosomes can downregulate HBx expression and inhibit hepatic stellate cell （HSC） activation. MethodsThe supernatants of HepG2， HepGA14， and CTL cells were collected to extract exosomes， which were referred to as NC－exo， HBV－exo， and CTL－exo， respectively）. Transmission electron microscopy was used to observe their morphology， and Western Blot was used to measure the expression of the markers of exosomes CD63 and TSG101. NC－exo， HBV－exo， and CTL－exo labeled by BODIPY dye were mixed with HBV－exo at different ratios and were then co－cultured with HSC LX－2 （HSC－LX2）. A fluorescence microscope was used to observe whether exosomes could enter LX－2 cells， and an fluorescence microscope was used to observe cell morphological changes； quantitative real－time PCR （qPCR） was used to measure the expression of the activated biomarkers such as transforming growth factor－β1 （TGF－β1）， ɑ－smooth muscle actin （ɑ－SMA）， and collagen type I （Collagen I） in LX－2 cells. CTL－exo was added to the HepGA14 culture system； then qPCR was used to measure the mRNA expression level of HBV DNA， cccDNA， and HBx in exosomes in HepGA14 cells， and Western Blot was used to measure the protein expression level of HBx in exosomes. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe exosomes were all microcysts with a double－layer membrane structure and were circular or elliptical in shape， with the expression of the signature proteins CD63 and TSG101， and the vesicles had a diameter of 50－100 nm. The fluorescence microscope showed that exosomes could enter LX－2 cells， and HSC were enlarged with extended cell processes. The results of qPCR showed that there were significant differences in the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes between the NC－exo， HBV－exo， NC－exo+HBV－exo， and Con groups （F=444.678， 417.144， and 571.508， all P<0.05）. After the intervention of HepGA14 cells with CTL－exo， qPCR results showed that compared with the control group， there were significant reductions in the expression levels of HBV DNA and cccDNA in HepGA14 cells （all P<0.05）， the relative mRNA expression level of HBx in exosomes （P<0.05）， and the protein expression level of HBx （P<0.05）. CTL－exo and HBV－exo were mixed at different ratios （2∶1， 5∶1， 10∶1） and were then used for the intervention of LX－2 cells， and qPCR results showed that the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes in LX－2 cells gradually decreased with the increase in the ratio of CTL－exo between groups （P<0.05）. ConclusionCTL－exo can downregulate the protein expression of HBx in HBV－exo to inhibit HSC activation， suggesting that CTL－exo has an anti－hepatitis B liver fibrosis effect.

BACKGROUND: After major liver resection, the volume status of patients is still undetermined. However, few concerns have been raised about postoperative fluid management. We aimed to compare gut function recovery and short-term prognosis of the patients after laparoscopic liver resection (LLR) with or without inferior vena cava (IVC) respiratory variability-directed fluid therapy in the anesthesia intensive care unit (AICU). METHODS: This randomized controlled clinical trial enrolled 70 patients undergoing LLR. The IVC respiratory variability was used to optimize fluid management of the intervention group in AICU, while the standard practice of fluid management was used for the control group. The primary outcome was the time to flatus after surgery. The secondary outcomes included other indicators of gut function recovery after surgery, postoperative length of hospital stay (LOS), liver and kidney function, the severity of oxidative stress, and the incidence of severe complications associated with hepatectomy. RESULTS: Compared with patients receiving standard fluid management, patients in the intervention group had a shorter time to anal exhaust after surgery (1.5 ± 0.6 days vs. 2.0 ± 0.8 days) and lower C-reactive protein activity (21.4 [95% confidence interval (CI): 11.9-36.7] mg/L vs. 44.8 [95%CI: 26.9-63.1] mg/L) 24 h after surgery. There were no significant differences in the time to defecation, serum concentrations of D -lactic acid, malondialdehyde, renal function, and frequency of severe postoperative complications as well as the LOS between the groups. CONCLUSION: Postoperative IVC respiratory variability-directed fluid therapy in AICU was facilitated in bowel movement but elicited a negligible beneficial effect on the short-term prognosis of patients undergoing LLR. TRIAL REGISTRATION ChiCTR-INR-17013093.
Humans ; Hepatectomy ; Vena Cava, Inferior/surgery* ; Liver ; Laparoscopy ; Fluid Therapy

The prevalence and recurrence rate of depressive disorder are high, while the recognition and cure rate are low. Early intervention can improve the quality of life of patients with depression. In clinical practice, it has been found that psychological treatments can effectively improve the symptoms and prognosis of depression.Cognitive behavior therapy(CBT) has been widely used in the treatment of depression, however, its mechanisms are still unclear. In this paper, the neuroimaging studies of patients with depression before and after CBT were summarized, and the structural or functional changes of different brain regions in patients with depression before and after CBT were described. The findings suggest that CBT improved depressive symptoms by increasing gray matter volume, activation level, and functional connectivity strength in the dorsolateral prefrontal cortex, reducing activation levels in the amygdala and parahippocampal gyrus, and restoring abnormal brain network activity or functional connectivity. Larger gray matter volume in anterior cingulate gyrus and higher activation levels in hippocampus and amygdala before treatment can effectively predict the effect of CBT in depressed patients. In the future, machine learning could be combined with brain imaging data to more accurately predict the effectiveness of CBT in treating depression.

Objective:To analyze the epidemiological characteristics of geriatric hip fractures.Methods:This study retrospectively analyzed the clinical characteristics of 2 054 elderly patients with hip fracture aged 60 years and over who were admitted to Beijing Hospital from January 2011 to December 2020.The epidemiological characteristics of geriatric hip fractures were analyzed from the aspects of age, gender, fracture type, length of stay, surgical method and surgical complications.Results:The total number of hip fractures patients admitted from 2011 to 2020 showed a general upward trend in quantity.Among them, there were 1 177 femoral neck fractures(57.3%, 1 177/2 054), and 877 intertrochanteric femoral fractures(42.7%, 877/2 054)with statistical differences in the distribution of fracture types between patients at different ages( χ2=61.727, P<0.001). A total of 1 839 patients chose surgical treatment, accounting for 89.5% of the total number of patients.Artificial femoral head arthroplasty was the most common operation mode for patients with femoral neck fractures(783 cases, 75.4%).534 patients with intertrochanteric femoral fractures(66.8%)were treated with closed reduction and femoral intramedullary nailing.There was a statistically significant difference in operation modes among different fracture types( χ2=1 480.800, P<0.001). The length of hospital stay in patients with femoral neck fracture was(14.2±8.3)days, which was significantly longer than in patients with femoral neck fracture(13.2±10.9)days( t=2.417, P=0.016). There was no significant difference in the time from admission to operation between the two groups[(5.7±3.5)days vs.(5.4±3.3)days]( t=1.954, P=0.051). Among all the comorbidities of hip fracture patients, the top 5 diseases were cardiovascular system diseases(2 001 cases, 97.4%), nervous system diseases(1 105 cases, 53.8%), endocrine system diseases(814 cases, 39.6%), skeletal and muscular system diseases(623 cases, 30.3%), digestive system diseases(472 cases, 23.0%).1 485 patients(72.3%)had 3 or more comorbidities. Conclusions:Hip fractures in the elderly have some epidemiological distribution characteristics in terms of age, gender, length of hospitalization, injury mechanism and comorbidities, which is conducive to further improve the prevention and treatment strategies for hip fractures and promote the rational allocation of medical resources.

Objective To investigate the influencing factors for ribavirin (RBV)-induced hemolytic anemia in the treatment of chronic hepatitis C, and to provide a reference for the early prediction of ribavirin-related hemolytic anemia in clinical practice. Methods A total of 49 patients with chronic hepatitis C who attended or were hospitalized in Hebei Petrochina Central Hospital from January 2018 to July 2019 and received antiviral therapy with direct-acting antiviral agent (DAA) and RBV were enrolled, with a major allele of C allele and a minor allele of A allele at the rs1127354 locus of the inosine triphosphate pyrophosphatase (ITPA) gene, and the patients with AA and AC genotypes were compared with those with CC genotype. During treatment, RBV was reduced to 600 mg when hemoglobin (Hb) level was < 100 g/L and was withdrawn when Hb level was < 85 g/L. Routine blood test, liver function, liver stiffness measurement, HCV RNA, HCV genotype, and ITPA genotype were measured before antiviral therapy, and the routine blood test was performed at weeks 2, 4, 8, and 12 of treatment. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. Results A total of 49 patients were enrolled in this study, among whom 22 had chronic hepatitis C and 27 had liver cirrhosis, with a sustained virologic response (SVR) rate of 95.9%. The dose of RBV was reduced in 3 patients (2 in the AA/AC group and 1 in the CC group) due to anemia, and RBV was withdrawn in 3 patients (1 in the AA/AC group and 2 in the CC group); all these 6 patients had liver cirrhosis and finally achieved SVR. During the anti-HCV therapy with DAA+RBV, there was relatively mild RBV-related hemolysis, and the maximum reduction in Hb from baseline was compared between the patients with AA/AC genotype at ITPA rs1127354 and those with CC genotype, which showed no significant difference between the two groups ( Z =-0.18, P =0.87). Conclusion During the treatment with RBV+DAA, RBV is withdrawn or reduced for liver cirrhosis patients due to anemia, and no obvious statistical relation is observed between ITPA genotype and the maximum reduction in Hb from baseline. Therefore, detection of ITPA genotype before the application of RBV does not improve safety during treatment, and it is not recommended to perform conventional detection of ITPA gene polymorphisms.

Objective To further verify the ability of noninvasive diagnostic method for liver fibrosis in predicting liver fibrosis in chronic hepatitis C patients followed up after sustained virologic response (SVR) based on liver biopsy. Methods A prospective cohort study was performed for the chronic hepatitis C patients who attended Beijing YouAn Hospital, Capital Medical University, from October 2015 to December 2017, and all patients were followed up regularly after SVR and underwent liver biopsy. The diagnostic efficiency of the noninvasive diagnostic method for liver fibrosis was verified based on pathological results. The receiver operating characteristic (ROC) curve was used to evaluate the ability of LSM, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis, and STATA and R language were used to compare the area under the ROC curve (AUC). Results A total of 96 patients were successfully enrolled. The LSM after SVR was significantly lower than that at baseline, and LSM had a significantly larger AUC than APRI (0.89 vs 0.67, P < 0.05) and FIB (0.89 vs 0.69, P < 0.05) in the diagnosis of liver cirrhosis after SVR. LSM at a cut-off value of 7.95 kPa, and based on the best specificity, the diagnosis of liver cirrhosis could be considered when LSM was greater than 9.15 kPa, with a positive likelihood ratio of 5.91%; progressive liver fibrosis could be excluded based on LSM < 6.85 kPa, with a negative predictive value of 0.98. Follow-up time and antiviral regimen had no influence on the diagnostic ability of LSM. Conclusion The cut off value of LSM needs to be lowered to predict liver fibrosis after SVR in chronic hepatitis C patients.