Colorectal cancer(CRC)is one of the most common malignant tumors worldwide,and its incidence has been increasing in recent years,especially among young adults.Non-genetic factors,such as dietary habits,lifestyle and intestinal flora,play an important role in the development of CRC.Dietary factors have a close relationship with CRC development.Insufficient fiber intake and excessive consumption of red and processed meat are generally considered major high-risk factors for CRC,while vegetables and fruits are considered as beneficial factors.The roles of calcium supplements,vitamin D,dairy products,and different dietary patterns in the development of CRC are still controversial.Furthermore,obesity,smoking,alcohol consumption,and lack of physical exercise are also associated with the risk of CRC.The imbalance of intestinal flora is also believed to be associated with the development of CRC.Optimizing dietary habits and maintaining a healthy lifestyle can significantly reduce the risk of CRC.Non-steroidal anti-inflammatory drugs and estrogen supplementation may have beneficial effects in reducing the risk of CRC.For certain individuals at high risk,pharmacological intervention may serve as an effective preventive measure.

Biological clock is a pattern of rhythms in which organisms exhibit cycles approaching 24 h in order to adapt to periodic changes in the external environment.Gut microbiota is the sum of extremely large number of microorganisms parasitized in humans and animals.Disorders of the biological clock increase the risk of metabolic diseases,and the occurrence of these disorders is closely related to the interaction with the dysbiosis of the gut microbiota.With the deepening of the understanding of the brain-gut axis,targeting gut microbiota to ameliorate biological clock disorders and associated diseases has achieved major theoretical breakthroughs and was partially applied in clinical practice,including dietary interventions such as time restricted feeding,development of microbial-related products(probiotics and postbiotics),and fecal microbiota transplantation.This article reviews the research progress of intestinal flora and rhythmicity,as well as targeting intestinal flora for the treatment of biological clock disorders,so as to provide new ideas for the prevention and treatment of rhythm disorders and concurrent diseases.

Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

Objective:Exploring the clinical efficacy of using ultra-thin lobulated anterolateral thigh perforator flap(ALTPF) with retrograde separation of perforating vessels from the superficial and deep junction layer of the superficial fascia to repair large soft tissue defects in the foot.Methods:From August 2021 to November 2022, 8 patients (5 males and 3 females) were admitted to the Second Department of Hand and Foot Surgery, the Affiliated Central Hospital of Dalian University of Technology. The patients were 28 to 52 years old in age. The soft tissue defects were located in dorsal and plantar foot. At the plantar foot, the wound involved the weight-bearing area with explosion of bone, tendon or internal fixtures. The area of soft tissue defects was 6.0 cm × 5.0 cm - 16.0 cm × 8.0 cm, and the sizes of ALTPF were 8.0 cm ×5.5 cm - 18.0 cm × 8.5 cm. Preoperative high frequency CUD combined with CTA angiography were employed to locate the 2 flap perforator vessels. By keeping the perforator vessels at center and according to the soft tissue defect area and the wound shape, an ALTPF with a proper size and shape was designed in anterolateral thigh. The perforator were separated in the boundary layer between superficial and deep fascia, where it helped to obviously thin the flap. After the flap was harvested, it was further lobulated between the 2 perforators into 2 lobes after having confirmed the effective blood supply. Finally the lobulated ALTPF was transferred to covered the defect in foot. Cautions should be taken to ensure that the flap covered the weight-bearing area of foot. All the donor sites were directly sutured. Postoperative follow-up was conducted to observe the survival of flaps and the functional recovery of the reconstructed site, also to evaluate the clinical effect. Postoperative follow-up included outpatient visits and reviews over WeChat or telephone. Recovery of the ankle motor function was evaluated according to the American Orthopedic Foot and Ankle Societ (AOFAS) ankle-hind foot score scale.Results:All 8 ALTPF survived. Over 6 to 18 months (10.8 months in average) of follow-up, the transferred flaps had good blood supply, soft in texture, with good elasticity and thin in appearance. Appearance and function of donor sites recovered well, except 1 patient who had mild scar hyperplasia. The plantar flap had good abrasion resistance. No flap damage, bleeding or granulation tissue hyperplasia occurred when walking. The mean score of AOFAS ankle-hind foot score achieved 95.6.Conclusion:The application of ultra-thin lobulated ALTPF with retrograde separation of perforating vessels from the superficial fascia at the junction layer for repairing large soft tissue defects in the foot has good clinical efficacy.

Objective:To retrospectively analyze the treatment of 25 cases of lower necrotizing fasciitis.Methods:A total of 25 patients with lower limb necrotizing fasciitis (13 males and 12 females), with mean age 63 years old (48-75 years old) in Dalian Municipal Central Hospital from September 2016 to December 2020. After admission, the patient′s general physical condition was strictly evaluated, the relevant preoperative examination was improved, and the necrotizing fasciitis laboratory risk index (LRINEC) score was performed. In the absence of surgical contraindication, multiple debridement was performed, leaving the necrotic tissue removed for general bacterial culture and drug sensitivity test in parallel. After debridement, eight patients showed a large area of skin necrosis, and amputation was selected. The other 17 patients chose limb protection treatment after debridement, and adopted debridement and free skin grafting. After surgery, patients were encouraged to strengthen rehabilitation exercise to restore limb function to the maximum extent.Results:With followed up 0.6 to 3.0 years, with an average of 1.8 years. Methods include outpatient return visit, WeChat contact or telephone inquiry. The skin survived in 17 patients with mean healing time (27.5 ± 6.9) d. Eighteen patients were multiple bacterial infections and seven patients were single bacterial infections. All patients had no joint dysfunction caused by scar contracture, and reinfection in the skin grafting area.Conclusions:Necrotizing fasciitis requires early diagnosis and early treatment, with correct choice of treatment method is closely related to the patient′s prognosis.

Objective: To investigate the efficacy of modified Quyuan decoction in the treatment of Children upper airway cough symptom complex with syndrome of phlegm and heat accumulated in lung. Methods: Eighty-two Children with upper airway cough symptom complex who met the inclusion criteria were randomly divided into 2 groups with 41 in each group. In the control group, monteluster sodium chewing tablets were taken orally and budesonide suspension was inhaled. The observation group took modified Quyuan decoction on the basis of the control group. Both groups were treated continuously for 2 weeks and followed up for 6 months. The levels of interleukin (IL)-8 and IL-13 were detected by double-antibody-sandwich ELISA, and the symptoms and signs were scored before and after treatment, as well as the symptoms of phlegm, heat and stagnation of lung, cough and pharynx. The efficacy was evaluated and recurrence rate was recorded. Results: The total effective rate 95.12% (39/41) in the observation group was obviously higher than 75.61% (31/41) in the control group (χ²=4.783, P=0.029). After treatment, the serum level of IL-8 (51.61 ± 5.94 ng/L vs. 71.25 ± 7.99 ng/L, t=12.631) and IL-13 (27.62 ± 3.20 ng/L vs. 34.91 ± 4.01 ng/L, t=9.099) in the observation group were significantly lower than those in the control group (P<0.01). After treatment, the scores of cough, nasal obstruction, runny nose, nasal itching, expectoration, sneezing, secretion of posterior pharyngeal wall and pharyngeal mucosa in the observation group were all significantly lower than those in the control group (t values were 7.762, 6.831, 6.217, 6.944, 6.408, 6.212, 7.268, 7.109, all Ps<0.01). The scores of cough, expectoration, blood in sputum, chest pain, dry mouth and fever were significantly lower than those of the control group (t values were 9.439, 6.831, 6.982, 10.115, 12.031 and 10.443, all Ps<0.01). Scores of daytime and nighttime cough symptoms were significantly lower than those of the control group (t values were 7.012, 7.241, respectively, all Ps<0.01). The scores of pharyngeal pain, pharyngeal dryness and pharyngeal foreign body sensation were significantly lower than those of the control group (t values were 6.003, 6.106, 6.318, respectively, all Ps<0.01). In the 6 months' follow-up observation, the recurrence rate was 17.7% (3/17) in the observation group and 53.9% (7/13) in the control group, and the difference between the two groups was statistically significant (χ²=4.344, P=0.037). Conclusions The modified Quyuan decoction combined with conventional western medicine can improve the symptoms and signs of upper airway cough symptom complex of children with syndrome of phlegm and heat accumulated in lung.

Objective To investigate the clinical effect of free bilateral anterolateral femoral perforator flap in repairing large area soft tissue defects of foot and ankle. Methods From July, 2013 to December, 2017, 30 pa-tients (19 males and 11 females) with large soft tissue defects of ankle and foot were treated , aged 21-52 years. The defects were located in the middle and distal part of the foot and ankle, the wounds were all exposed with bone, ten-don or internal fixator, and the area of skin defect was 15 cm × 22 cm-19 cm× 28 cm. All of them were repaired by free bilateral anterolateral femoral perforator flaps. The perforating branch of bilateral flap was determined by CDU or DSA before operation. According to the area of skin defect and the shape of wound, an appropriate perforating branch flap was designed in the anterolateral thigh region. One perforating branch flap was used as the proximal series flap, the proximal vessel pedicle was anastomosed with the recipient region arteriovenous flap. The other perforating branch flap was used as the distal series flap, the artery and vein were anastomosed between the two flaps. The total area of the two flaps was 17 cm × 25 cm-23 cm × 32 cm. The survival of the flap and the functional recovery of the repair site were observed and the clinical effect was evaluated. Results There was no vascular crisis after operation, and the flaps survived. Followed-up for 5-28(mean, 13.5)months showed that the flap had good blood flow, soft texture and good elasticity, among which 4 cases were slightly bloated and improved after plastic operation. After operation, 26 cases were excellent (90-100 points), 4 cases were good (75-89 points), and the average score of AOFAS was 93.8 points. Conclusion The traffic accident of anterolateral perforating branch and the attention in the process of flap cutting and series were summarized.

Objective To investigate softening-hardness dissipating-binds effects of Fuzheng Huayu (reinforcing-healthy qi resolving-stasis)Tablet combined with anti-virus therapy on liver fibrosis, and relationship between these effects and regulation of pathway of miR-122-interleukin-10-reactive oxygen species(miR-122/IL-10/ROS).Methods The patients with chronic hepatitis and liver fibrosis(n=85)were chosen from Aug.2015 to Aug.2016,and then divided randomly into test group(n=45)and control group(n=40).The control group was treated with entecavir(0.5 mg/d)and monoammonium glycyrrhizinate(0.1 g/d),and test group, additionally with Fuzheng Huayu Tablet(4.5 g/d)for 48 weeks.After treatment,ISHAK fibrosis score was reviewed through routine pathology, and activities of serum superoxide dismutase(SOD)and ROS were detected by using ELISA.The expressions of miR-122 mRNA and IL-10 mRNA were detected by using RT-PCR, and content of serum inflammatory factors of liver fibrosis, including procollagen III N-terminal peptide(PCIIINP), type IV collagen(IV-C), hyaluronidase(HA)and laminin(LN),were detected by using immunoturbidimetry.Results ISHAK fibrosis score had no significant difference between 2 groups before treatment,and decreased in 2 groups after treatment,which was superior in test group to that in control group(P<0.05).The content of serum inflammatory factors of liver fibrosis all decreased in 2 groups after treatment,and the decreases of PCIIINP and HA were more significant in test group compared with control group(P <0.05).The activities of ROS and SOD had no difference in 2 groups before treatment,and ROS decreased in 2 groups after treatment.The inhibitory effect on ROS was better in test group than that in control group after treatment(P<0.05), and SOD increase was effectively relieved in test group after treatment(P <0.05).The expressions of miR-122 mRNA and IL-10 mRNA all decreased in 2 groups after treatment, which was more significant in test group compared with control group(P<0.05).Conclusion Fuzheng Huayu Tablet reduces directly the levels of collagen and HA, degrades abnormal deposition of extracellular matrix,and regulates dynamic balance of collagen,and it antagonizes effectively the genetic expressions of IL-10 and miR-122,relieves inflammatory disorders and controls progress of histology.

Vanishing bile duct syndrome (VBDS) manifests as progressive destruction and disappearance of the intrahepatic bile duct caused by various factors and cholestasis. VBDS associated with drug-induced liver injury (D-VBDS) is an important etiology of VBDS, and immune disorder or immune imbalance may be the main pathogenesis. According to its clinical symptoms, serological markers, and course of the disease, D-VBDS is classified into major form and minor form, and its clinical features are based on various pathomorphological findings. Its prognosis is associated various factors including regeneration of bile duct cells, number of bile duct injuries, level and range of bile duct injury, bile duct proliferation, and compensatory shunt of bile duct branches. This disease has various clinical outcomes; most patients have good prognosis after drug withdrawal, and some patients may experience cholestatic cirrhosis, liver failure, and even death. Due to the clinical manifestation and biochemical changes are similar to the primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), it need to identify by clinical physician.