Interferon (IFN)-mediated pathways are a crucial part of the cellular response against viral infection. Type III IFNs, which include IFN-λ1, 2 and 3, mediate antiviral responses similar to Type I IFNs via a distinct receptor complex. IFN-λ1 is more effective than the other two members. Transcription of IFN-λ1 requires activation of IRF3/7 and nuclear factor-kappa B (NF-κB), similar to the transcriptional mechanism of Type I IFNs. Using reporter assays, we discovered that viral infection induced both IFN-λ1 promoter activity and that of the 3'-untranslated region (UTR), indicating that IFN-λ1 expression is also regulated at the post-transcriptional level. After analysis with microRNA (miRNA) prediction programs and 3'UTR targeting site assays, the miRNA-548 family, including miR-548b-5p, miR-548c-5p, miR-548i, miR-548j, and miR-548n, was identified to target the 3'UTR of IFN-λ1. Further study demonstrated that miRNA-548 mimics down-regulated the expression of IFN-λ1. In contrast, their inhibitors, the complementary RNAs, enhanced the expression of IFN-λ1 and IFN-stimulated genes. Furthermore, miRNA-548 mimics promoted infection by enterovirus-71 (EV71) and vesicular stomatitis virus (VSV), whereas their inhibitors significantly suppressed the replication of EV71 and VSV. Endogenous miRNA-548 levels were suppressed during viral infection. In conclusion, our results suggest that miRNA-548 regulates host antiviral response via direct targeting of IFN-λ1, which may offer a potential candidate for antiviral therapy.
3' Untranslated Regions ; Adult ; Antiviral Agents ; pharmacology ; therapeutic use ; Base Sequence ; Down-Regulation ; drug effects ; Female ; Hep G2 Cells ; Hepatitis B, Chronic ; drug therapy ; metabolism ; pathology ; Humans ; Interferon Regulatory Factor-3 ; metabolism ; Interferon Regulatory Factor-7 ; metabolism ; Interleukins ; antagonists & inhibitors ; genetics ; metabolism ; Leukocytes, Mononuclear ; metabolism ; Male ; MicroRNAs ; metabolism ; Middle Aged ; NF-kappa B ; metabolism ; Poly I-C ; pharmacology ; therapeutic use ; Promoter Regions, Genetic ; RNA Interference ; RNA, Small Interfering ; metabolism

Objective:To investigate the efficacy of robot-assisted femoral tunnel localization in reconstruction of the medial patellofemoral ligament (MPFL).Methods:A retrospective study was conducted to analyze the 36 patients who had been admitted to Department of Sports Medicine, The Fourth Hospital of Wuhan between January 2019 and January 2022 due to recurrent patellar dislocation. There were 15 males and 21 females; age: 23.5 (18.3, 29.0) years; number of dislocations: 2.5 (2.0, 3.0). They were stratified into 2 cohorts based on utilization of robot-assistance. In the observation group (17 cases), the femoral tunnel localization was robot-assisted in MPFL reconstruction; in the control group (19 cases), the femoral tunnel localization was guided by C-arm fluoroscopy in MPFL reconstruction. The 2 groups were compared in terms of operation time, frequency of guide wire placement, visual analogue scale (VAS) at postoperative 1 d, patellar tilt angle (PTA) and the disparity between actual femoral tunnel insertion and ideal tunnel insertion point (Sch?ttle point) at postoperative 1 to 3 d, and Lysholm knee score and International Knee Documentation Committee (IKDC) score at the last follow-up.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for 12.0 (10.3, 13.0) months. In the observation group, the operation time [(64.1±16.7) min], frequency of guide wire placement [1.0 (1.0, 2.0) times], VAS [2.5 (2.0, 3.0) points], and disparity between actual femoral tunnel insertion and ideal tunnel insertion point [(4.7±1.2) mm] were significantly better than those in the control group [(84.2±19.7) min, 3.0 (2.0, 4.0) times, 3.5 (3.0, 4.0) points, and (6.1±1.2) mm] ( P<0.05). There was no statistical difference between the 2 groups in PTA, Lysholm knee score or IKDC score ( P>0.05). Conclusions:The short-term clinical efficacy of robot-assisted femoral tunnel localization is satisfactory in MPFL reconstruction. Compared with the intraoperative C-arm fluoroscopy, robot-assisted localization can decrease the frequency of guide wire placement, enhance femoral tunnel accuracy and efficiency, and alleviate more postoperative pain for the patients.

Objective:To investigate the early clinical effect of fascia lata autograft bridging combined with the long head of biceps tendon transposition for treatment of irreparable massive rotator cuff tear.Methods:All of 31 cases of massive irreparable rotator cuff tear treated in our hospital from March 2016 to March 2020 were analyzed retrospectively. Among them, 17 cases (10 males, 7 females) were repaired with fascia lata autograft bridging under arthroscopy (patch group), the average age was 61.47±6.63 (ranging from 51 to 72) and 14 cases (4 males, 10 females) were repaired with fascia lata autograft bridging combined with the long head of biceps tendon transposition (combined group), the average age was 62.57±6.11 (ranging from 53 to 71). The operation time, intraoperative blood loss, postoperative complications, visual analogue scale (VAS) of pain before operation, at 1 week and 12 months after operation, Constant-Murley score of shoulder joint and American Association of shoulder and elbow Surgeons (ASES) score before operation, at 6 months and 12 months after operation were compared between the two groups. The outcome of rotator cuff healing was evaluated by MRI 1 year after operation.Results:All patients were followed up for 12-27 months (mean 18.33 ±6.8 months). There was no perioperative complication, and there was no significant difference in operation time between the two groups ( P>0.05) . The VAS score in the patch group was significantly higher than the combined group 1 week after operation ( t=2.09, P=0.048) , and there was no significant difference in VAS score 12 months after operation between the two groups. Constant-Murley score and ASES score in the combined group were significantly higher than the patch group at 6 months after operation ( t=5.23, P<0.001; t=4.45, P<0.001) , and there was no significant difference in Constant score and ASES score between the two groups at 12 months after operation. Constant score and ASES score in the two groups were significantly higher than those before operation. One year after operation, the MRI of the affected shoulder showed that the incidence of autograft patch thinning (Sugaya grade III) was 52.94%, the autograft patch structure failure rate (Sugaya grade IV and V) was 17.65% in the patch group, the autograft patch thinning rate (Sugaya grade III) was 35.71%, and the structural failure rate (Sugaya grade IV and V) was 7.14% in the combined group. The difference was statistically significant (χ 2=7.12, P=0.028) . Conclusion:Fascia lata autograft patch bridging combined with long head of biceps tendon transposition technique for treatment of irreparable massive rotator cuff tear has less pain 1 week after operation and better recovery of shoulder function half a year after operation. MRI showed better patch healing 1 year after operation.

OBJECTIVE: To explore the effect of chitosan (CS) hydrogel loaded with tendon-derived stem cells (TDSCs; hereinafter referred to as TDSCs/CS hydrogel) on tendon-to-bone healing after rotator cuff repair in rabbits. METHODS: TDSCs were isolated from the rotator cuff tissue of 3 adult New Zealand white rabbits by Henderson step-by-step enzymatic digestion method and identified by multidirectional differentiation and flow cytometry. The 3rd generation TDSCs were encapsulated in CS to construct TDSCs/CS hydrogel. The cell counting kit 8 (CCK-8) assay was used to detect the proliferation of TDSCs in the hydrogel after 1-5 days of culture in vitro, and cell compatibility of TDSCs/CS hydrogel was evaluated by using TDSCs alone as control. Another 36 adult New Zealand white rabbits were randomly divided into 3 groups ( n=12): rotator cuff repair group (control group), rotator cuff repair+CS hydrogel injection group (CS group), and rotator cuff repair+TDSCs/CS hydrogel injection group (TDSCs/CS group). After establishing the rotator cuff repair models, the corresponding hydrogel was injected into the tendon-to-bone interface in the CS group and TDSCs/CS group, and no other treatment was performed in the control group. The general condition of the animals was observed after operation. At 4 and 8 weeks, real-time quantitative PCR (qPCR) was used to detect the relative expressions of tendon forming related genes (tenomodulin, scleraxis), chondrogenesis related genes (aggrecan, sex determining region Y-related high mobility group-box gene 9), and osteogenesis related genes (alkaline phosphatase, Runt-related transcription factor 2) at the tendon-to-bone interface. At 8 weeks, HE and Masson staining were used to observe the histological changes, and the biomechanical test was used to evaluate the ultimate load and the failure site of the repaired rotator cuff to evaluate the tendon-to-bone healing and biomechanical properties. RESULTS: CCK-8 assay showed that the CS hydrogel could promote the proliferation of TDSCs ( P<0.05). qPCR results showed that the expressions of tendon-to-bone interface related genes were significantly higher in the TDSCs/CS group than in the CS group and control group at 4 and 8 weeks after operation ( P<0.05). Moreover, the expressions of tendon-to-bone interface related genes at 8 weeks after operation were significantly higher than those at 4 weeks after operation in the TDSCs/CS group ( P<0.05). Histological staining showed the clear cartilage tissue and dense and orderly collagen formation at the tendon-to-bone interface in the TDSCs/CS group. The results of semi-quantitative analysis showed that compared with the control group, the number of cells, the proportion of collagen fiber orientation, and the histological score in the TDSCs/CS group increased, the vascularity decreased, showing significant differences ( P<0.05); compared with the CS group, the proportion of collagen fiber orientation and the histological score in the TDSCs/CS group significantly increased ( P<0.05), while there was no significant difference in the number of cells and vascularity ( P>0.05). All samples in biomechanical testing failed at the repair site during the testing process. The ultimate load of the TDSCs/CS group was significantly higher than that of the control group ( P<0.05), but there was no significant difference compared to the CS group ( P>0.05). CONCLUSION TDSCs/CS hydrogel can induce cartilage regeneration to promote rotator cuff tendon-to-bone healing.
Rabbits ; Animals ; Rotator Cuff/surgery* ; Chitosan ; Hydrogels ; Rotator Cuff Injuries/surgery* ; Wound Healing ; Tendons/surgery* ; Collagen ; Stem Cells ; Biomechanical Phenomena

Objective: To analyze risk factors of anastomotic leakage after McKeown'sesophagectomy. Methods: The clinical data of 635 esophageal cancer patients, who underwent McKeown's esophagectomy at Cancer Hospital of Chinese Academy of Medical Sciences from January 2012 to December 2015, were retrospectively analyzed. The risk factors of cervical anastomotic leakage were identified through analysis of medical history, surgical procedure, tumor characteristics and vascular calcification. Results: Among all the 635 patients, anastomotic leakage occurred in 111 (17.5%)patients. Univariate analysis showed that the American Society of Anesthesiologists (ASA) risk class, prior thoracic surgery, upper digestive tract ulcer, COPD, hypertension, peripheral vascular disease, renal insufficiency, FEV1% predicted, DLCO% predicted, duration of surgery and calcification of descending aorta, celiac trunk and left postceliac arteries were associated with a statistically significant increase in risk of cervical anastomotic leakage (P<0.05 for all). Logistic regression analysis showed that ASA risk class, peripheral vascular disease, renal insufficiency and calcification of descending aorta and celiac trunk were independent risk factors of cervical anastomotic leakage after McKeown's esophagectomy (P<0.05 for all). Conclusions ASA risk class, peripheral vascular disease, renal insufficiency, calcification of descending aorta and celiac trunk are independent risk factors of cervical esophageal anastomotic leakage after McKeown's esophagectomy.

OBJECTIVETo explore the pattern of lymph node metastasis and evaluate the modes and extent of mediastinal lymph node dissection in patients with ≤ 3 cm, clinical stage I primary non-small cell lung cancer (NSCLC).

METHODSData of 270 eligible patients who underwent pulmonary resection with systematic lymph node dissection in our hospital between March 2012 and August 2013 were retrospectively analyzed in order to investigate the relationship between the clinicopathological features and lymph node metastatic patterns. Patients with multiple primary carcinomas or non-primary pulmonary malignancies and those who received any chemotherapy or radiotherapy or did not undergo systematic nodal dissection were excluded. The criteria of systematic nodal dissection included the removal of at least six lymph nodes from at least three mediastinal stations, one of which must be subcarinal. The data were analyzed and compared using Chi-square test.

RESULTSThe postoperative morbidity rate was 14.8% and no death occurred in this series. The imaging findings showed 34 cases of pure ground glass opacity lesions, 47 partial solid nodules, and 189 solid nodules. Apart from 34 p-GGO lesions, among the other 236 cases, ≤ 1 cm lesions were in 22 cases, 1 cm- ≤ 2 cm lesions in 138 cases, and >2 cm- ≤ 3 cm lesions in 76 cases based on radiologic findings. The pathological types included adenocarcinoma (n = 245), squamous cell carcinoma (n = 18) and other rare types (n = 7). The overall lymph node metastasis rate was 18.9% (51/270), and the incidence of lymph node involvement was 0(0/34) in cancers with p-GGO, 2.1% (1/47) in mixed solid nodules, 26.5% (50/189) in solid nodules, 18.2% (4/22) in nodules ≤ 1 cm, 14.5% (20/138) in 1 cm < nodules ≤ 2 cm, and 35.5% (27/76) in 2 cm < nodules ≤ 3 cm. The metastasis rates of non-specific tumor-draining region lymph nodes detected in the patients with positive and negative lobe-specific lymph node involvement were 20.0%-50.0% vs. 0-2.9% (P < 0.001).

CONCLUSIONSUsually NSCLC with p-GGO nodules has no lymph node metastasis, therefore, systematic nodal dissection may be not necessary. The larger the tumor size is, the higher the lymph node metastatic rate is for mixed or solid nodules. Intraoperative frozen-section examination of the lobe-specific lymph nodes should be performed routinely in patients with ≤ 2 cm stage I NSCLC, and systematic nodal dissection should be done if positive, but it may be not necessary if negative. However, the effectiveness of the systematic selective lymph node dissection still needs to be further confirmed.

Carcinoma, Non-Small-Cell Lung ; diagnosis ; surgery ; Humans ; Lymph Node Excision ; methods ; Lymph Nodes ; surgery ; Lymphatic Metastasis ; diagnosis ; Neoplasm Staging ; Retrospective Studies

OBJECTIVEVideo-assisted thoracoscopic (VATS) esophagectomy has been performed for more than 10 years in China. However, compared with the conventional esophagectomy via right thoracotomy, whether VATS esophagectomy has more advantages or not in the lymph node (LN) dissection and prevention of perioperative complications is still controversial and deserves to be further investigated. The aim of this study was to explore whether there are significant differences in this issue between the two surgical modalities or not.

METHODSThe results of lymph node dissection and perioperative complications as well as other parameters in the patients treated by VATS esophagectomy and those by conventional esophagectomy via right thoracotomy at our department from May 1, 2009 to July 30, 2013 were compared using SPSS 16.0 in order to investigate whether there was any significant difference between these two treatment modalities in the learning curve stage of VATS esophagectomy.

RESULTSOne hundred and twenty-nine cases underwent VATS esophagectomy between May 1, 2009 and July 30, 2013, and another part 129 cases with the same preoperative cTNM stage treated by conventional esopahgectomy via right thoracotomy were selected in order to compare the results of lymph node dissection and perioperative complications as well as other parameters between those two groups of patients. There were no significant differences in the sex, age, lesion locations and cTNM stage between these two groups. The total LN metastatic rate in the VATS esophagectomy group was 35.7% and that of the conventional esophagectomy group was 37.2% (P > 0.05). The total average number of dissected lymph nodes was 12.1 vs. 16.2 (P < 0.001). The average dissected LN stations was 3.2 vs. 3.6 (P = 0.038). The total average number of dissected LN along the left recurrent laryngeal nerve was 2.0 vs. 3.7 (P = 0.012). The total average number of dissected LN along the right recurrent laryngeal nerve was 2.9 vs. 3.4 (P = 0.231). However, there was no significant difference in the total average number of dissected LN in the other thoracic LN stations, and in the perioperative complications between the two groups. The total postoperative complication rate was 41.1% in the VATS group versus 42.6% in the conventional group (P = 0.801). The cardiopulmonary complication rate was 25.6% vs. 27.1% (P = 0.777). The death rate was the same in the two groups (0.8%). The VATS group had less blood infusion (23.2% vs. 41.8%, P = 0.001) and shorter hospital stay (15.9 days vs. 19.2 days, P = 0.049) but longer operating time (161.3 min vs. 127.8 min, P < 0.01).

CONCLUSIONSIn the learning curve stage of VATS esophagectomy, compared with the conventional esophagectomy, less LN number and stations can be dissected in the VATS group due to un-skillful VATS manipulation, especially it is more difficult in the LN dissection along the left recurrent laryngeal nerve. Therefore, it is more suitable to select patients with early esophageal cancer without obvious enlarged lymph nodes for VATS esophagectomy in the learning curve stage.

China ; Esophageal Neoplasms ; pathology ; surgery ; Esophagectomy ; adverse effects ; methods ; Humans ; Learning Curve ; Length of Stay ; Lymph Node Excision ; adverse effects ; methods ; statistics & numerical data ; Lymph Nodes ; Operative Time ; Postoperative Complications ; epidemiology ; Recurrent Laryngeal Nerve ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thoracotomy

BACKGROUNDIn order to minimize the injury reaction during the surgery and reduce the morbidity rate, hence reducing the mortality rate of esophagectomy, minimally invasive esophagectomy (MIE) was introduced. The aim of this study was to compare the postoperative outcomes in patients with esophageal squamous cell carcinoma undergoing minimally invasive or open esophagectomy (OE).

METHODSThe medical records of 176 consecutive patients, who underwent minimally invasive esophagectomy (MIE) between January 2009 and August 2013 in Cancer Institute & Hospital, Chinese Academy of Medical Sciences, were retrospectively reviewed. In the same period, 142 patients who underwent OE, either Ivor Lewis or McKeown approach, were selected randomly as controls. The clinical variables of paired groups were compared, including age, sex, Charlson score, tumor location, duration of surgery, number of harvested lymph nodes, morbidity rate, the rate of leak, pulmonary morbidity rate, mortality rate, and hospital length of stay (LOS).

RESULTSThe number of harvested lymph nodes was not significantly different between MIE group and OE group (median 20 vs. 16, P = 0.740). However, patients who underwent MIE had longer operation time than the OE group (375 vs. 300 minutes, P < 0.001). Overall morbidity, pulmonary morbidity, the rate of leak, in-hospital death, and hospital LOS were not significantly different between MIE and OE groups. Morbidities including anastomotic leak and pulmonary morbidity, inhospital death, hospital LOS, and hospital expenses were not significantly different between MIE and OE groups as well.

CONCLUSIONSMIE and OE appear equivalent with regard to early oncological outcomes. There is a trend that hospital LOS and hospital expenses are reduced in the MIE group than the OE group.

Aged ; Carcinoma, Squamous Cell ; surgery ; Esophageal Neoplasms ; surgery ; Esophagectomy ; methods ; Female ; Humans ; Laparoscopy ; Length of Stay ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Thoracoscopy ; Treatment Outcome

Objective: The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods: We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results: The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% (P<0.001) and 3-year DFS were 72.0%, 44.7%, 17.6% (P<0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3-year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7% of the negative group (both P<0.001). The 3-year OS and DFS of pathologic stage Ⅰ, Ⅱ, ⅢA, ⅢB and Ⅵ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3% (P<0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3% (P<0.001), respectively.The operation-related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS (P<0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.