Liver fibrosis and cirrhosis are the common outcomes of various chronic liver diseases after progression,and studies have shown that liver fibrosis and early liver cirrhosis can be reversed.Compound traditional Chinese medicine prescriptions have a marked therapeutic effect in reversing liver fibrosis and early liver cirrhosis,and their mechanism of action remains unclear.By reviewing related articles in China and globally,this article summarizes the six main phenotypic mechanisms involved in the efficacy of compound traditional Chinese medicine prescriptions,i.e.,inhibiting liver inflammation and regulating liver immune response,regulating hepatic stellate cell activation and extracellular matrix(ECM)generation,promoting ECM degradation,reversing hepatic sinusoidal capillarization,regulating hepatocyte regeneration,and regulating gut microbiota,and in addition,this article also analyzes the advances and shortcomings in current studies on each phenotype.Future studies on compound traditional Chinese medicine prescriptions should focus on experimental exploration and rescue experiments to verify the above phenotypes and further explore the upstream and downstream signaling pathways with a marked effect.This article aims to help clarify the direction and ideas of studies on the therapeutic mechanism of compound traditional Chinese medicine prescriptions,in order to provide a basis for clarifying the scientific essence of compound traditional Chinese medicine prescriptions.

OBJECTIVE To investigate the improvement effects of 3，5，6，7，8，3′，4′-heptamethoxyflavone （HMF） of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group， model group， positive control group （Raceanisodamine tablet， 1 mg/kg）， HMF low-dose， medium-dose and high-dose groups （0.3， 0.6， 0.9 mg/kg）， with 7 rats in each group. Except for the normal group， the other groups were modeled by internal and external composite factors. After successful modeling， the rats in each group were given the corresponding drug or normal saline， once a day， for 14 days. The general behavioral states such as dietary intake， water intake and mental state of the rats were observed， and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin （HE） staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected， and the expression of aquaporins （AQP3） in the gastric tissue of rats was determined. RESULTS Compared with the normal group， the dietary intake and water intake of the model group rats were significantly decreased （P＜0.01）， the fecal water content rate， salivary flow rate， plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly （P＜0.01）. Gastric tissue injury invaded the mucosal muscle layer， resulting in mucosal muscle layer rupture； pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group， the dietary intake and water intake of rats were increased in HMF groups； fecal water content rate， salivary flow rate， plasma content of aldosterone， the expression of AQP3 in gastric tissue were decreased， most of the above differences were statistically significant （P＜0.05 or P＜0.01）. The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer， the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Objective:To measure the morphological parameters of distal tibiofibular syndesmosis in healthy adults using multi-slice CT (MSCT) so as to provide a reference for the diagnosis of distal tibiofibular syndesmosis injury.Methods:The ankle MSCT imaging data in 110 normal adults were retrieved from the image report database of Cangzhou People′s Hospital from May 2019 to May 2021, including 56 males and 54 females; aged 18-60 years [(38.2±11.0)years]. There were 51 patients with imaging on the right ankle and 59 on the left ankle. Picture archiving and communication system (PACS) was used to measure parameters at 10 mm above the articular surface of the distal tibia on MSCT, including the anterior tibiofibular space (L1), posterior tibiofibular space (L2), middle tibiofibular space (L3), depth of fibula in notch (L4), distance of anterior tibiofibular edge (L5), distance of posterior tibiofibular edge (L6), anterior tibiofibular syndesmosis angle (A1), and fibular rotation angle (A2), and the measurements were compared by sex, age and side. The positive rate of "tibiofibular line" was observed. The morphological classification of distal tibiofibular syndesmosis was performed.Results:There was no significant difference in L1-L6, A1 and A2 among different age and side (all P>0.05). No significant difference was found in L4, L5, A1 and A2 between males and females ( P>0.05), but L1, L2, L3 and L6 were larger in males than in females ( P<0.05 or 0.01). The positive rate of "tibiofibular line" was 80.4% (45/56) in males compared to 74.1% (40/54) in females ( P>0.05), 77.2% (44/57) in the youth compared to 77.4% (41/53) in the middle-aged, and 78.0% (46/59) in the left ankle compared to 76.5% (39/51) in the right ankle (all P>0.05). Morphological classification of distal tibiofibular syndesmosis was crescent in 61 patients (55.5%), trapezoid in 14 (12.7%), I-shaped in 3 (2.7%), M-shaped in 17 (15.5%), V-shaped in 10 (9.1%), Г-shaped in 5 (4.5%). Conclusions:When L1, L2, L3 and L6 are used as references in the diagnosis of adult distal tibiofibular syndesmosis injury, gender factors rather than age or side factors should be considered. Males have wider distal tibiofibular space than females, with the fibula more forward. The "tibiofibular line" has a high positive rate and is not affected by gender, age or sides, providing a new idea for the diagnosis of distal tibiofibular syndesmosis injury and anatomical reduction. There are many variations in the morphology of distal tibiofibular syndesmosis, so it is easy to be misdiagnosed as the separation of distal tibiofibular syndesmosis on X-ray, which should be noted.

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Chyle leak or chyle ascites is a specific form of lymphatic leakage after radical laparoscopic colorectal cancer surgery,the incidence of which has been reported in the literature to be 1％-6.5％,leading to the development of hydropower imbalance,malnutrition,impaired immune function,prolonged hospital stay and even an impact on oncological prognosis.Different surgical sites,number of lymph nodes dissected,duration of surgery,prognostic nutritional index,metastasis of the main lymph nodes,operator and age are risk factors for postoperative chyle leak in colorectal cancer.It usually occurs 4-8 days after surgery and is characterized by a sudden increase of drainage after eating which is milky,odourless and tasteless,and may be combined with abdominal pain,bloating and increased body temperature.After prolonged chyle leak,patients may develop water-electrolyte disturbance,malnutrition and hypoproteinemia.The chyle test is useful in the qualitative diagnosis of chyle leak and can be performed to detect triglyceride concentrations.Conservative treatment is the preferred treatment strategy for chyle leak,and if conservative treatment fails,surgery may be considered.Knowledge of the distribution pattern of colorectal lymphatic drainage and precise control of lymph node dissection are key measures to prevent chyle leak after laparoscopic colorectal cancer surgery.

The treatment strategy for colon cancer with liver metastasis has always been a great challenge for clinical surgeons.Single treatment method such as surgical resection or systemic chemotherapy can no longer meet the treatment needs of such patients.With the extensive development of the multi-disciplinary team(MDT)for colorectal cancer based on surgery,more and more patients with advanced colorectal cancer have obtained better treatment effects and survival benefits.A case of descending colon cancer with huge hepatic metastasis diagnosed and treated by a multi-disciplinary team was reported,aiming to provide reference for clinical practice.

Stage T4 colon cancer is divided into two categories:tumor penetrating the visceral peritoneum(T4a)and tumor directly invading or attaching to adjacent organs or structures(T4b).Treatment of T4 colon cancer requires technically demanding surgical procedures,including total resection of adjacent infiltrating organs or structures,and is characterized by a high incidence of postoperative complications and a high rate of positive surgical margin microscopy.It has been found that taking laparoscopic surgery for T4 colon cancer may decrease long-term survival and increase the rate of peritoneal metastasis,but taking laparoscopic surgery for colon cancer also has the potential advantages in increasing perioperative benefits and improving the prognosis.With the upgrade of laparoscopic equipment and the improvement of surgeons'surgical skills,more and more surgeons have adopted laparoscopic surgery to treat T4 colon cancer.Currently,the oncologic safety of laparoscopic surgery for T4 colon cancer has not been effectively evaluated.Therefore,this article reviews the advantages,risks,and the choice of treatment strategies for laparoscopic surgery for T4 colon cancer,taking into account the current status and progress of domestic and international studies.

Objective:To evaluate the hip C-arm fluoroscopy at primary position in internal fixation of femoral neck fracture.Methods:A retrospective study was conducted of the 69 patients with femoral neck fracture who had been treated from August 2015 to August 2018.They were divided into a primary position group ( n=35) subjected to C-arm hip fluoroscopy at primary position under symmetry traction of bilateral lower limbs for reduction of femoral neck fracture and a control group ( n=34) subjected to C-arm hip fluoroscopy at frog’s position on the healthy side for traction and reduction of the injured hip. The 2 groups were compared in terms of fluoroscopy frequency, times of resetting guide pin, intraoperative blood loss and total operation time. Results:The 2 groups were comparable due to insignificant significances between them in the preoperative general data like gender, age, fracture type, injury cause, or interval from injury to operation ( P>0.05). Compared with the control group, the primary position group showed less intraoperative fluoroscopy (7.2 times ± 0.5 times versus 16.1 times ± 1.2 times), fewer times of resetting guide pin (2.1 times ± 0.31 times versus 4.7 times ± 0.8 times), less intraoperative blood loss (96.8 mL ± 18.6 mL versus 198.1 mL ± 13.2 mL), and shorter total operation time (1.2 h ± 0.2 h versus 1.6 h ± 0.3 h). All the differences were statistically significant ( P<0.05). Conclusions:C-arm hip fluoroscopy at primary position may protect the stability after fracture reduction because bilateral lower limbs are under symmetrical traction and the hip position needs no alteration. Operation of C-arm fluoroscopy is easy and convenient and produces clear images. Therefore, this new mode of fluoroscopy has advantages of less intraoperative fluoroscopy and guide pin resetting, leading to significantly reduced intraoperative blood loss, ineffective operation time and anesthesia time.