BACKGROUND:There are many studies focusing on keloid scars,but the pathogenesis is not fully understood.In recent years,there have been some new research advances in the pathogenesis of keloids,including transforming growth factor-β(TGF-β)/Smad signaling pathway,ischemic hypoxia,hypoxia-inducible factor 1(HIF-1),and mitogen-activated protein kinase(MAPK)pathway.The TGF-β/Smad pathway is now more clearly studied,and activation of the TGF-β/Smad pathway promotes the development of keloid scars. OBJECTIVE:To review the TGF-β/Smad signaling pathway and evaluate the main therapeutic strategies targeting this pathway,with the aim of contributing to the development of more effective clinical treatments. METHODS:PubMed and Web of Science,CNKI and WanFang databases were searched by computer for relevant literature published from January 2017 to April 2023 with the search terms of"keloid,fibroblasts,TGF-β/Smad,extracellular matrix,collagen,treatment measures"in English and Chinese.Seventy-two articles were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The mechanism of TGF-β/Smad signaling pathway in the occurrence and development of keloids is summarized:TGF-β1 and TGF-β2 are overexpressed in keloids,while TGF-β3 shows antifibrotic effects.Smad2/3 and Smad1/5/8 are combined with Smad4 to form a complex that enters the nucleus and plays a fibrotic role,while Smad6/7 can inhibit keloid hyperplasia.The TGF-β/Smad signaling pathway is currently the most clearly studied pathway in keloids,and there are many pathways targeted to inhibit the activation of this pathway,which can inhibit the occurrence and development of keloids to a greater extent.Currently,there is no single clinical gold standard treatment for keloids,and inhibition of the TGF-β/Smad pathway alone cannot completely inhibit the development of keloids.A comprehensive consideration of the association between all systemic systems and keloids is needed.Although many promising targets have been identified in the fibrosis cascade,more research is needed to translate this into targeted therapies in the clinic.

Objective:To explore the correlation between attempted suicide and childhood trauma as well as inflammatory cytokines levels in adolescents with depressive disorder.Methods:From January to December 2021, a total of 164 adolescents with depressive disorder were included and categorized into attempted suicide group ( n=108) and non-attempted suicide group ( n=56) according to whether they accompanied attempted suicide or not. The Chinese version of the suicide module of MINI 5.0, the childhood trauma questionnaire(CTQ), and the center for epidemiological studies depression scale (CES-D) were used to assess suicidal behavior, childhood trauma and depressive symptoms, while the plasma inflammatory cytokines levels were measured by electrochemiluminescence technology. The data were statistically analyzed by SPSS 23.0 software. Logistic regression was applied to analyze the independent influencing factors of attempted suicide and the predictive value of each independent risk factor for attempted suicide was assessed by receiver operating characteristic curve(ROC) curves. Results:The prevalence of attempted suicide was 65.9%(108/164) in adolescents with depressive disorder.The univariate analyses showed that the total CTQ score ((55.19±12.44), (45.50±12.11)) ( t=-4.771, P<0.001), CES-D total score ((40.75±10.26), (32.98±13.39)) ( t=-4.131, P<0.001), IL-6 level(1.87 (1.32, 2.69) pg/mL, 1.56 (1.05, 1.87) pg/mL)( Z=-3.102, P=0.002), IL-10 level (0.53 (0.38, 0.83) pg/mL, 0.47 (0.31, 0.69) pg/mL) ( Z=-2.100, P=0.036) and IL-17A level (2.20 (1.52, 3.65) pg/mL, 1.67 (1.25, 2.97) pg/mL) ( Z=-2.254, P=0.024) in plasma of patients in the attempted suicide group were significantly higher than those in non-attempted suicide group. Logistic stepwise regression analyses showed that CTQ total score, IL-6, IL-10, and IL-17A were risk factors for attempted suicide in adolescents with depressive disorder.The ROC showed that the total score of CTQ combined with IL-6 (AUC=0.782, 95% CI=0.709-0.855, P<0.001), the total score of CTQ combined with IL-10 (AUC=0.765, 95% CI=0.688-0.841, P<0.001), and the total score of CTQ combined with IL-17A (AUC=0.762, 95% CI=0.684-0.840, P<0.001) had a larger area under the curve, indicating better recognition and prediction ability for attempted suicide, with high sensitivity and specificity. Conclusion:The incidence of attempted suicide in adolescents with depressive disorder is high, and which is closely related to childhood trauma and the levels of inflammatory cytokines.

Neoadjuvant chemoradiotherapy is a part of the current standard treatment mode for locally advanced rectal cancer,which enables a certain proportion of patients to achieve complete tumor response,improving the surgical resection rate and anal retention rate,and then prolonging the disease-free survival period of patients.MRI is the preferred imaging examination to evaluate the efficacy of neoadjuvant therapy.With the development of functional MRI,quantitative parameters derived from different imaging principles can provide more biological information about tumors,improving the clinical application value of MRI.Multi-parameter MRI combining conventional MRI sequences and functional sequences can more comprehensively evaluate the efficacy of neoadjuvant therapy,which is conducive to developing individualized treatment plans for patients in clinical practice and realize precision medicine.

Objective To investigate whether 3D-guided cone-shaped segmentectomy can achieve comparable long-term outcomes with lobectomy for deep early-stage lung cancer with diameter≤2 cm. Methods We retrospectively screened patients with deep early-stage non-small cell lung cancer (NSCLC) with diameter≤2 cm who underwent lobectomy or segmentectomy in the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018. All pulmonary segmentectomy was performed using 3D-guided cone-shaped segmentectomy with segment or subsegment as the resection unit. Univariate and multivariate regression analyses were performed by Cox proportional hazard regression model. The patients who underwent segmentectomy and lobectomy were matched 1∶1 by propensity-score matching analysis. The oncological outcomes of two groups were compared. Results Our cohort was divided into a segmentectomy group (n=222) and a lobectomy group (n=127). The age, total nodule size, solid component size and proportion of pure solid nodule in the lobectomy group were significantly higher than those in the segmentectomy group. The median follow-up time was 49 months. Surgical margins were negative in all patients. The local recurrence rate of segmentectomy was 0.45%. The disease-free survival (DFS) rate and overall survival (OS) rate of patients in the segmentectomy group were significantly better than those in the lobectomy group (5-year DFS rate: 98.64% vs. 89.77%, P<0.001; 5-year OS rate: 99.55% vs. 92.10%, P<0.001). Multivariate regression analysis showed that the differences between two groups were not significant [DFS rate: HR=0.52. 95%CI (0.11, 2.59), P=0.427; OS rate: HR=0.08. 95%CI (0.00, 3.24), P=0.179] after adjusting for other factors. After propensity score matching, 77 patients were preserved in both segmentectomy group and lobectomy group, with the mean nodule size of 1.44 cm and 1.49 cm and the mean consolidation tumor ratio (CTR) of 0.46 and 0.52, respectively. There was no statistical difference in DFS rate (P=0.640) or OS rate (P=0.310) between the two groups. Conclusion 3D-guided cone-shaped segmentectomy can be an acceptable treatment for low-grade malignant NSCLC deep in lung parenchyma with diameter≤2 cm, and its oncology effect is not inferior to lobectomy.

Objective To analyze the mechanism that Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei(B.pseudomallei)mediates the formation of multinucleated giant cells(MNGCs)when host cells are infected by the bacterium.Methods The mutant strain(BPC006 Δhcp1)and complementation strain(BPC006 Δhcp1::hcp1)were constructed by homologous recombination and plasmid complement technology,respectively.After RAW264.7 cells were infected with B.pseudomallei,the localization of Hcp1 in host cells was analyzed by immunofluorescence staining.The localization was further verified by cytoplasmic-membrane isolation in 293T cells after transfecting pCDNA4.1-Hcp1.The biological significance and effect of Hcp1 were explored by the anti-Hcp1 polyclonal antibody blocking and the formation of MNGC was detected by Giemsa staining.Results Western blotting showed that BPC006 Δhcp1 could not express Hcp1,while BPC006 Δhcp1::hcp1 restored Hcp1 expression.The above results proved that the mutant and complement strains were successfully constructed.Both cellular immunofluorescence co-localization and cytoplasmic-membrane isolation experiments showed that Hcp1 localized to host cell membranes.Last but not least,compared with the control group,anti-Hcp1 polyclonal antibodies inhibited the formation of MNGC(P＜0.01).Conclusion Hcp1 protein in type Ⅵ secretion system of B.pseudomallei is able to translocate to the RAW264.7 cell membranes and plays an important role in the formation of MNGCs.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .

Objective To explore the correlation between contrast sensitivity and binocular visual function in indi-viduals with high myopia,aiming to understand how binocular visual function impacts contrast sensitivity in this popula-tion.Methods In this cross-sectional study,a total of 33 patients(66 eyes)with high myopia attending the Optometric Center of Tianjin Eye Hospital from March to December 2020 were included.They were measured for oculomotor parame-ters as well as binocular contrast sensitivity in photopic and scotopic conditions.According to the type of functional indica-tors to which the oculomotor parameters belong,they were divided into two groups:accommodation and vergence.The oculomotor parameters of accommodation include accommodative amplitude(AMP),monocular accommodative facility(MAF)and binocular accommodative facility(BAF);the oculomotor parameters of vergence include distance lateral pho-ria(DLP),near lateral phoria(NLP),positive fusional vergence(PFV),negative fusional vergence(NFV),and vergence facility(VF),among them,PFV includes the near and distance PFV breaking points and recovery points,and NFV includes the near and distance NFV breaking points and recovery points.Pearson bivariate correlation analysis was used to analyze the bivariate correlations between binocular contrast sensitivity and the oculomotor parameters of accommodation and ver-gence.In addition,canonical correlation analysis was used to analyze the associations between binocular contrast sensitivi-ty and accommodation and vergence indicators in patients with high myopia.Results The spherical equivalent refraction of the participants was(-9.51±2.71)D in the left eye and(-10.00±2.88)D in the right eye.The bivariate correlation analysis showed that among the oculomotor parameters of accommodation,the AMP of the left eye was negatively correla-ted with the contrast sensitivity at 18 c·d-1 under scotopic conditions(r=-0.406,P=0.019);among the oculomotor pa-rameters of vergence,the near PFV breaking point was positively correlated with the contrast sensitivity at 1.5 c·d-1(r=0.458)and3.0 c·d-1(r=0.441)under scotopic conditions(both P＜0.05),the near PFV recovery point was positively correlated with the contrast sensitivity at 3.0 c·d-1(r=0.351)and 6.0 c·d-1(r=0.396)under photopic conditions(both P＜0.05)and positively correlated with contrast sensitivity at 1.5 c·d-1(r=0.449),3.0 c·d-1(r=0.537)and 12.0 c·d-1(r=0.375)under scotopic conditions(all P＜0.05),and VF was positively correlated with contrast sensitivity at 1.5 c·d-1(r=0.358)under photopic conditions and 3.0 c·d-1(r=0.458)under scotopic conditions(both P＜0.05).Except for the above indicators,other oculomotor parameters of accommodation and vergence were not correlated with contrast sensitivity(all P＞0.05).Canonical correlation analysis showed that only the oculomotor parameters of vergence were correlated with the first pair of canonical correlation coefficients of contrast sensitivity under scotopic conditions(P=0.008)and the canonical correlation coefficient was 0.912.The oculomotor parameters of convergence U1 were mainly de-termined by NLP,near NFV recovery point,near PFV breaking point,and near PFV recovery point.Contrast sensitivity V,under scotopic conditions was mainly determined by contrast sensitivity at 1.5 c·d-1 and 6.0 c·d-1under scotopic condi-tions.The typical structural analysis showed that there was a strong positive correlation of U1 with near PFV breaking point and contrast sensitivity at 1.5 c·d-1 under scotopic conditions;there was a strong positive correlation of V1 with near PFV breaking point and contrast sensitivity at 1.5 c·d-1 under scotopic conditions.Conclusion There is an association be-tween vergence and contrast sensitivity under scotopic conditions among high myopia patients.Improving binocular visual function may enhance contrast sensitivity and overall visual quality in high myopia patients.

To investigate the evaluation and management of gastrointestinal fistula after upper gastrointestinal tunnel endoscopic surgery, a retrospective analysis was performed on 15 patients with gastrointestinal fistula after upper gastrointestinal tunnel endoscopic surgery, who were treated at the Endoscopy Center of Zhongshan Hospital, Fudan University from January 2012 to October 2022. All patients were treated successfully after comprehensive treatment. Three patients received metal clipping and gastric tube drainage; 10 patients received gastric tube drainage combined with jejunal nutritional tube placement, and 7 of them had gastric tube directly put into the fistula cavity; 2 patients received covered esophageal stent placement combined with jejunal nutritional tube placement. Five patients received wound tissue glue spraying; 2 patients underwent purse-string suture with nylon loops and metal clips after reduced fistula burned by hot biopsy forcep or argon plasma coagulation. The gastrointestinal fistula after tunnel endoscopic surgery is a complex postoperative complication, which needs early detection, careful evaluation and comprehensive treatment.

Objective:To understand the sales characteristics and salt iodine content in urban and rural salt market of Guizhou Province.Methods:In accordance with the "Guizhou Province 2020 Iodine Deficiency Disorders Monitoring Field Technical Guidance Work Program", 14 counties (cities, districts) from 88 counties (cities, districts) of 9 cities (states) in Guizhou Province were selected in August 2020. Each county (city, district) selected the urban area and a representative township, and at least 2 supermarkets were selected from the urban area, and 5 supermarkets or retail stores from the townships as the investigation sites, to collect the label information of all commercially available salt within the scope of investigation. At the same time, salt samples were collected after excluding the same brand, variety, and specification, and salt iodine was detected by redox titration.Results:A total of 107 labels of commercially available salt were collected, involving 21 brands, of which Biyuan brand had the largest number (53 samples, 49.5%) and the widest sales range, involving 12 counties (cities, districts). Salt producing areas came from 13 provinces, and the salt produced in Sichuan Province was the most widely distributed in the surveyed area (36 samples), followed by Chongqing Municipality (17 samples) and Hubei Province (16 samples). There were 19 brands (75 samples) and 7 brands (32 samples) of salt sold in urban and rural areas, respectively, and the main brand was Biyuan, accounting for 38.7% (29/75) and 75.0% (24/32), respectively. There were 8 brands (27 samples) and 16 brands (80 samples) of salt sold in retail stores and supermarkets, respectively, and the main brand was Biyuan, accounting for 66.7% (18/27) and 43.8% (35/80), respectively. Among 107 salt samples, it was found that the labeled iodine content did not meet the Guizhou Province salt iodization implementation standard (21 - 39 mg/kg), and only 39 samples (36.4%) had electronic anti-counterfeiting traceability codes on their labels. After excluding the same brand, variety, and specification, the median salt iodine of the 51 salt samples was 23.6 mg/kg, ranging from 19.2 to 38.1 mg/kg, and 21 - 39 mg/kg accounted for 96.1% (49/51).Conclusions:There are many salt brands sold in urban and rural areas in Guizhou Province, and the electronic traceability platform needs to be improved. Salt iodine is mainly distributed in the low-value area of the standard range, which brings potential risks to the sustainable and effective prevention and control of iodine deficiency disorders.

Objective : To analyze the correlation between Ki⁃67 expression and EGFR mutations in lung adenocarcinoma and reveal their prognostic roles. Methods : This study retrospectively screened lung adenocarcinoma patients who underwent surgical treatment between 2014 and 2020 in our department. Clinicopathological characteristics , Ki⁃67 expression and EGFR mutations were collected. The chi⁃square , Student ’s t ⁃test and ANOVA were used for the comparison of Ki⁃67 expression and EGFR mutations among the groups. The Spearman ’s rho was adopted to evaluate the correlation between Ki⁃67 expression and EGFR mutations. Finally , the Log⁃rank test was used to reveal the prognostic roles of Ki⁃67 expression and EGFR mutations in lung adenocarcinoma. Results : A total of 673 lung adenoca~rcinoma samples were enrolled in this study. The mean expression of Ki⁃67 was 21. 37 ± 20. 43 [ Median : 15(6 30)] . Among these subjects , 462 samples harbored EGFR mutations (68. 65% ) . The expression of Ki⁃67 was much higher in males and smokers , and was positively correlated with tumor size and lymph node metastasis. The frequency of EGFR mutations was higher in females and non⁃smokers , and was negatively correlated with tumor size and lymph node metastasis. Samples with EGFR mutations had a lower Ki⁃67 expression level than those without EGFR mutations ( 18. 82 ± 17. 75 vs 26. 97 ± 24. 45 , P < 0. 001) . Consistently , the frequency of EGFR mutations in samples with a lower expression level of Ki⁃67 was significantly higher than that in patients with a higher Ki⁃67 expression (74. 1% vs 57. 0% , P < 0. 001) . The Spearman ’s rho analysis indicated that a higher Ki-67 expression and EGFR wild type were significantly associated with a poorer prognosis of lung adenocarcinoma ( P <0. 05 ). The combined analysis of Ki-67 expression and EGFR mutations indicated that EGFR wild type patients with Ki-67 > 10 had a poorer prognosis than subjeets with Ki-67 <10 and EGFR mutations. What's more , the HR value was 4. 46 (95% CI: 1. 91 10. 73 , P < 0. 001) . Conclusion Ki⁃67 expression was significantly negatively correlated with EGFR mutations in lung adenocarcinoma. Ki⁃67 expression and EGFR mutations might have a combined effect on the prognosis of lung adenocarcinoma.