[Full-cycle, multidisciplinary and systematic management of citrin deficiency].

Professor Takeyori Saheki's team at Kagoshima University, Japan, published a paper in Nature Genetics in June 1999, pinpointing the pathogenic gene for adult-onset type Ⅱ citrullinemia as SLC25A13 and naming the protein product encoded by this gene as citrin. Over the past 25 years, the researches have made positive progress on the pathophysiological mechanism, clinical phenotype, molecular diagnosis, treatment, and prognosis of citrin deficiency (CD) as an autosomal recessive genetic disease. Currently, three age-dependent clinical phenotypes of CD have been found, namely neonatal intrahepatic cholestasis caused by citrin deficiency, failure to thrive and dyslipidemia caused by citrin deficiency, and adult-onset type Ⅱ citrullinemia. Although relevant internal medicine drugs are being researched and developed while liver transplantation has been used for the treatment of CD patients, scientific dietary therapy remains the foundation, core, and key for the management of this disease. Furthermore, CD management involves the full life cycle of patients, requiring the joint efforts of basic and clinical medicine as well as systematic articulation at multi-levels, such as the parents, family, and society. By full-cycle, multidisciplinary, and systematic management, it is an achievable goal for CD patients to learn, work, and live in a healthy manner.

[Safety and efficacy analysis of a varicose vein sealant kit in the treatment of great saphenous vein dysfunction].

Objective: To investigate the safety and efficacy of a varicose vein sealant kit in the treatment of great saphenous vein dysfunction. Methods: It was a randomized controlled trial. A total of 180 patients with great saphenous vein dysfunction were enrolled prospectively, and scheduled for surgical treatment in 9 hospitals, including the Second Affiliated Hospital of Naval Medical University, Shanghai Oriental Hospital Affiliated to Tongji University, Xuanwu Hospital Capital Medical University, the First Hospital of Hebei Medical University, Ganzhou People's Hospital, Shanxi Bethune Hospital, the Second Affiliated Hospital of Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, and Zhongshan Hospital Affiliated to Xiamen University, from June to October 2022. Using a random number table method, the subjects were divided into an experimental group and a control group, with 90 cases in each group. The patients of experimental group received treatment with varicose vein sealant kit, while the patients of control group received radiofrequency ablation. The main outcome measure was the complete closure rate of the great saphenous vein in both groups of patients 3 months after surgery. The secondary outcome measures were the complete closure rate of the great saphenous vein in both groups of patients immediately after surgery and 6 months after surgery, the operation time for closing the main trunk of the great saphenous vein, pain score, venous clinical severity score (VCSS), Aberdeen varicose veins questionnaire (AVVQ) at different times before and after surgery, and the incidence of complications in both groups of patients. The non inferiority threshold for the two treatment methods is set at "-10.00%". Results: A total of 177 patients were ultimately enrolled. There were 89 cases in the experimental group, including 38 males and 51 females, with a median age [M (Q1, Q3)] of 59.7(49.6, 66.7) years, and 88 cases in the control group, including 30 males and 58 females, with a median age of 57.2(46.9, 65.9) years. A total of 174 patients completed a 3-month follow-up, and 167 patients completed a 6-month follow-up. The closure time of the main saphenous vein in the experimental group was (22.1±11.1) min, which was longer than the control group, which was (18.7±9.8) min (P=0.031). The complete closure rate of the great saphenous vein immediately after surgery in both the experimental group and the control group was 100%. The complete closure rates of the great saphenous vein at 3 months after surgery were 98.8% (85/86) and 98.9% (87/88), respectively. The lower limit of the 95%CI for the difference between the two groups was -3.19%, which was greater than the non-inferiority threshold of -10.00% (non-inferiority P<0.001). The complete closure rates of the great saphenous vein at 6 months after surgery were 97.6% (81/83) and 100% (84/84), the lower limit of the 95%CI for the difference between the two groups was -5.71%, which was greater than the non-inferiority threshold of -10.00% (non-inferiority P<0.001). The immediate pain scores after complete anesthesia awakening of the experimental group and the control group were both 1.0 (0, 2.0), with no statistically significant difference (P=0.365). The incidence of bruising in the experimental group and the control group one week after surgery was 61.2% (52/85) and 67.1% (57/85), respectively, with no statistically significant difference (P=0.181). There was no statistically significant difference in VCSS and AVVQ scores between groups before surgery and at 1, 3, and 6 months after surgery (all P>0.05). There was no statistically significant difference in the incidence of complications such as deep vein thrombosis, phlebitis, pain, and subcutaneous hematoma in the lower limbs 3 months after surgery (all P>0.05). Conclusion: The varicose vein sealant kit is safe and effective in treating great saphenous vein dysfunction, and can achieve a complete closure rate of great saphenous vein that is not inferior to traditional radiofrequency ablation.

[Detection of colorectal advanced neoplasms among the cancer screening population in urban areas of Henan Province and analysis on its influencing factors].

Objective: To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors. Methods: A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results: A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio (OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion: The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.

Cortisol secretion autonomy associated with weight loss outcome after laparoscopic sleeve gastrectomy: a prospective cohort study in Asian patients.

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is a widely recognized effective bariatric surgery. However, variable weight loss outcomes post-surgery remained a clinical challenge. Currently, there is no established consensus on the factors influencing weight loss failure following LSG. This study aimed to explore the association between preoperative cortisol secretion autonomy and postoperative weight loss in obese patients undergoing LSG. PATIENTS AND METHODS: A cohort of 181 patients with simple obesity (BMI ≥ 28 kg/m2) who underwent LSG and were followed up for one year was analyzed. Weight loss was measured by the percentage of excess weight loss (%EWL), and cortisol secretion autonomy was evaluated using a 1 mg dexamethasone suppression test (DST). Regression models were used to analyze the correlation between preoperative 1 mg DST results and %EWL one year after laparoscopic sleeve gastrectomy (LSG). RESULTS: Cortisol secretion autonomy was significantly lower in the %EWL ≥ 75% group and higher in the %EWL < 75% group, showing a negative correlation with %EWL (R = -0.336, p = 0.001). Logistic regression analysis indicated that high cortisol secretion autonomy was significantly correlated with %EWL < 75% after LSG. The likelihood of %EWL being < 75% was 10.47 times greater in patients with high cortisol secretion autonomy compared to those with low cortisol secretion autonomy (odds ratio 10.472, confidence interval: 1.660-66.048, p = 0.012). CONCLUSIONS: Cortisol secretion autonomy emerges as an independent predictor of weight loss outcomes in Asian patients undergoing LSG. This finding suggests the potential for cortisol secretion autonomy to inform preoperative assessments and personalized treatment strategies in bariatric surgery.

[Intermittent exotropia complicated with spasm of the near reflex: a case report].

A 21-year-old female patient presented to the Ophthalmology Department of Yunnan University Affiliated Hospital with complaints of "bilateral blurred vision accompanied by diplopia for 3 weeks". The patient's main symptoms included intermittent visual blurring, diplopia, headaches, and ocular discomfort. Ocular examination revealed intermittent exotropia, sometimes accompanied by esotropia or orthotropia, along with signs of pupillary constriction and pseudomyopia. Based on the clinical presentation, a diagnosis of intermittent exotropia complicated by spasm of the near reflex (SNR) was made. The patient underwent bilateral exotropia surgery, which corrected the ocular alignment and resolved the symptoms and signs of SNR postoperatively.

[Clinicopathological characteristics of gangliogliomas with anaplastic morphology].

Objective: To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity. Methods: Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling. Results: Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation. Conclusions: AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

[Recognition of unilateral auditory neuropathy in children].

Objective: This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN. Methods: A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children's Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software. Results: (1) The UAN group (77.8%) had a significantly higher rate of ABR wave IIIL than the SSD group (20.9%) (P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN (P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ²=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) (Fisher's exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type (P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups (P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ²=6.695, P=0.015). Conclusions: Compared to children with SSD, the occurrence of wave IIIL on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.

[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

[Computer-vision-based artificial intelligence for detection and recognition of instruments and organs during radical laparoscopic gastrectomy for gastric cancer: a multicenter study].

Objective: To investigate the feasibility and accuracy of computer vision-based artificial intelligence technology in detecting and recognizing instruments and organs in the scenario of radical laparoscopic gastrectomy for gastric cancer. Methods: Eight complete laparoscopic distal radical gastrectomy surgery videos were collected from four large tertiary hospitals in China (First Medical Center of Chinese PLA General Hospital [three cases], Liaoning Cancer Hospital [two cases], Liyang Branch of Jiangsu Province People's Hospital [two cases], and Fudan University Shanghai Cancer Center [one case]). PR software was used to extract frames every 5-10 seconds and convert them into image frames. To ensure quality, deduplication was performed manually to remove obvious duplication and blurred image frames. After conversion and deduplication, there were 3369 frame images with a resolution of 1,920×1,080 PPI. LabelMe was used for instance segmentation of the images into the following 23 categories: veins, arteries, sutures, needle holders, ultrasonic knives, suction devices, bleeding, colon, forceps, gallbladder, small gauze, Hem-o-lok, Hem-o-lok appliers, electrocautery hooks, small intestine, hepatogastric ligaments, liver, omentum, pancreas, spleen, surgical staplers, stomach, and trocars. The frame images were randomly allocated to training and validation sets in a 9:1 ratio. The YOLOv8 deep learning framework was used for model training and validation. Precision, recall, average precision (AP), and mean average precision (mAP) were used to evaluate detection and recognition accuracy. Results: The training set contained 3032 frame images comprising 30 895 instance segmentation counts across 23 categories. The validation set contained 337 frame images comprising 3407 instance segmentation counts. The YOLOv8m model was used for training. The loss curve of the training set showed a smooth gradual decrease in loss value as the number of iteration calculations increased. In the training set, the AP values of all 23 categories were above 0.90, with a mAP of 0.99, whereas in the validation set, the mAP of the 23 categories was 0.82. As to individual categories, the AP values for ultrasonic knives, needle holders, forceps, gallbladders, small pieces of gauze, and surgical staplers were 0.96, 0.94, 0.91, 0.91, 0.91, and 0.91, respectively. The model successfully inferred and applied to a 5-minutes video segment of laparoscopic gastroenterostomy suturing. Conclusion: The primary finding of this multicenter study is that computer vision can efficiently, accurately, and in real-time detect organs and instruments in various scenarios of radical laparoscopic gastrectomy for gastric cancer.

[Interpretation of global lung cancer statistics].

Lung cancer remains one of the leading cause of global cancer-related mortality, posing a significant burden of disease. Tobacco exposure stands as the foremost risk factor for lung cancer. Since the 1960, global efforts have gradually been implemented to control tobacco exposure, consequently reducing tobacco exposure levels within populations. This shift in exposure levels may have altered the epidemiological characteristics of lung cancer globally. This study aims to describe global lung cancer incidence data across five dimensions: age, gender, region, stage at diagnosis, and survival status, using global cancer registry data and relevant research findings. The objective is to elucidate the current epidemiological features of lung cancer worldwide, providing a scientific basis for lung cancer prevention and control. Furthermore, this study offers corresponding measures and recommendations for lung cancer prevention and control, aligning with the three-tiered cancer prevention strategy. Findings indicate that the incidence and mortality burden of lung cancer is significantly higher among the elderly population (aged 65 years and above) compared to the working-age population (aged 15-64 years). The aged-standardized incidence rate of lung cancer remains higher in males than in females, but the overall aged-standardized incidence rate of lung cancer in males shows a declining trend, while that in females shows an increasing trend. Regions with high and very high human development index (HDI) exhibit a substantially higher incidence and mortality burden of lung cancer compared to regions with low and very low HDI. Japan ranks highest in the diagnosis of stage Ⅰ lung cancer, with a diagnosis rate of 38.6%. Its age-standardized 5-year net survival rate is relatively high at 32.9%. Despite improvements in the survival status of lung cancer in certain countries like China and Japan, the overall prognosis for lung cancer remains pessimistic. Given the current epidemiological characteristics of lung cancer, reinforcing tobacco control measures and reducing female-specific lung cancer risk factors stand as significant goals for primary prevention. Promoting low-dose computed tomography screening for high-risk population, minimizing false-positive rates in lung cancer screening, and promoting medical system reforms and standardized treatment constitute principal measures for secondary and tertiary lung cancer prevention, respectively.

[Real-time localization for port-implanted catheter tip by echocardiographic guidance].

The clinical data of 23 patients undergoing real-time echocardiography-guided infusion port implantation in the Breast Center of Tsinghua Changgung Hospital in Beijing from January to July 2021 were analyzed. The length of catheter insertion L1 was initially estimated using surface measurement method in all patients. Intraoperatively, transthoracic echocardiography was applied using the parasternal four-chamber view to visualize the catheter image within the right atrium, and the length of catheter insertion L2 was recorded under the guidance of echocardiography. Postoperatively, chest radiographs were taken in the upright position to observe the position of the catheter tip. According to chest CT scans, the ideal length (L) for catheter tip placement was calculated when it was located at the junction of superior vena cava and right atrium. Bland-Altman scatter plot analysis and linear regression fitting test were used on L1 and L2 respectively with L to evaluate the consistency. A total of 23 patients were included in this study, among which one case of left breast cancer patient undergoing breast-conserving surgery had difficulty in identifying the catheter tip position due to residual pleural effusion obscuring the imaging of the cardiac apex four-chamber view. In 22 patients, the results of intraoperative ultrasound imaging were good, including 1 case of catheter ectopic to azygos vein, and 21 cases of right atrial catheter could be detected by ultrasound. Statistical analysis showed that there was a good consistency between L1 and L, L2 and L, and the difference between them was d=0.28 cm (95%CI:-1.76-2.31 cm) and d=0.20 cm(95%CI:-0.84-1.23 cm), respectively, with no statistical significance (P>0.05). In the linear regression model, L2 and L had a higher fit than L1, and the difference was statistically significant (R²=0.954, P<0.001). This study found that real-time echocardiographic localization technique can be applied in adult port surgery to replace X-ray-guided real-time catheter tip detection and adjustment to the optimal position.

Remnant cholesterol is associated with hip BMD and low bone mass in young and middle-aged men: a cross-sectional study.

PURPOSE: Remnant cholesterol (RC) is a contributor to cardiovascular diseases, obesity, diabetes, and metabolic syndrome. However, the specific relationship between RC and bone metabolism remains unexplored. Therefore, we aimed to investigate the relationships of RC with hip bone mineral density (BMD) and the risk of low bone mass. METHODS: Physical examination data was collected from men aged < 60 years as part of the Kailuan Study between 2014 and 2018. The characteristics of the participants were compared between RC quartile groups. A generalized linear regression model was used to evaluate the relationship between RC and hip BMD and a logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for low bone mass. Additional analyses were performed after stratification by body mass index (BMI) (≥ or < 24 kg/m2). Sensitivity analyses were performed by excluding individuals who were taking lipid-lowering therapy or had cancer, cardiovascular diseases, or diabetes. RESULTS: Data from a total of 7,053 participants were included in the analysis. After adjustment for confounding factors, RC negatively correlated with hip BMD (ß = - 0.0079, 95% CI: - 0.0133, - 0.0025). The risk of low bone mass increased from the lowest to the highest RC quartile, with ORs of 1 (reference), 1.09 (95% CI: (0.82, 1.44), 1.35 (95%CI: 1.02, 1.77), and 1.43 (95% CI: 1.09, 1.89) for Q1, Q2, Q3, and Q4, respectively (P for trend = 0.004) in the fully adjusted model. Compared to RC < 0.80 mmol/l group, the risk of low bone mass increased 39% in RC ≥ 0.80 mmol/l group (P < 0.001). The correlation between RC and hip BMD was stronger in participants with BMI ≥ 24 kg/m2 group (ß = - 0.0159, 95% CI: - 0.0289, - 0.0029). The results of sensitivity analyses were consistent with the main results. CONCLUSION: We have identified a negative correlation between serum RC and hip BMD, and a higher RC concentration was found to be associated with a greater risk of low bone mass in young and middle-aged men.

[Current status of global colorectal cancer prevalence, prevention and control].

Objective: This paper provides a brief overview of the epidemiology of colorectal cancer in China and around the world, and discusses how to prevent colorectal cancer to reduce its disease burden. Method: Using the official database of GLOBOCAN 2020, the China Cancer Registry Annual Report compiled by the National Cancer Center, and data from CONCORD-3.Data management was performed by Microsoft Excel 2016 and R 4.2.1 Relevant graphs were generated using the ggplot2 package for result visualization. Result: An estimated 1 931 590 people were diagnosed with colorectal cancer worldwide in 2020 with an age-standardized incidence rate of 19.5 per 100 000. There were about 935 173 deaths caused by colorectal cancer internationally, with an age-standardized mortality rate of 9.0 per 100 000. Overall, colorectal cancer was the fourth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. In China, the age-standardized incidence rate and mortality rate of colorectal cancer was 17.3 per 100 000 and 7.8 per 100 000, respectively. Gender differences in trends were observed, with a decreasing trend in incidence and mortality among females and an increasing trend in incidence and mortality among males. The primary risk factors for colorectal cancer include age, genetic factors, gastrointestinal disorders, dietary habits, and lifestyle et al. Conclusions: Colorectal cancer poses a significant burden globally and in China. The occurrence of colorectal cancer is closely related to physiology, genetics, behavioral habits, lifestyle, and disease factors. To better control the colorectal cancer burden with the lowest cost, specific measures should be taken to reduce exposure to established risk factors. By combining the disease prevention and control strategies of tertiary prevention in China with the characteristic factors of colorectal cancer, the incidence and mortality of colorectal cancer may be effectively controlled.

[Clinical effect of modified vertical rectus abdominis myocutaneous flap in repairing skin and soft tissue defects after abdominoperineal resection for rectal cancer].

Objective: To investigate the clinical effect of the modified vertical rectus abdominis myocutaneous flap in repairing the skin and soft tissue defect after abdominoperineal resection for rectal cancer. Methods: This study was a retrospective observational study. From June 2019 to July 2022, five male patients with low rectal cancer who were conformed to the inclusion criteria were admitted to the Department of Basic Surgery of Xiangya Hospital of Central South University, with ages ranging from 65 to 70 years and the sizes of the perianal skin ulcers ranging from 5 cm×4 cm to 11 cm×9 cm, and all of them underwent abdominoperineal resection. The secondary skin and soft tissue defects in the perineum with an area of 8 cm×6 cm-14 cm×12 cm (with the depth of pelvic floor dead space being 10-15 cm) were repaired intraoperatively with transplantation of modified vertical rectus abdominis myocutaneous flaps with the skin area being 9 cm×7 cm-16 cm×12 cm, the volume of the muscle being 18 cm×10 cm×5 cm-20 cm×12 cm×5 cm, and the vessel pedicle being 18-20 cm in length. During the operation, most of the anterior sheath of the rectus abdominis muscle was retained, the flap was transferred to the recipient area through the abdominal cavity, the remaining anterior sheaths of the rectus abdominis muscle on both sides of the donor area were repeatedly folded and sutured, the free edge of the transverse fascia of the abdomen was sutured with the anterior sheath of the rectus abdominis muscle, and the donor area skin was directly sutured. After the operation, the survival of the transplanted myocutaneous flap was observed. The occurrence of complications in the perineal recipient area was recorded within 2 weeks after the operation. The recovery of the perineal recipient area and the abdominal donor area was observed during follow-up, and the occurrence of complications in the donor area of the abdomen as well as the recurrence of tumors and metastasis were recorded. Results: All transplanted myocutaneous flaps in 5 patients survived after surgery. One patient had dehiscence of the incision in the perineal recipient area 2 days after surgery, which healed after 7 d with intermittent dressing changes and routine vacuum sealing drainage treatment. In the other 4 patients, no complications such as incisional rupture, incisional infection, or fat liquefaction occurred in the perineal recipient area within 2 weeks after surgery. Follow-up for 6-12 months after discharge showed that the skin of the perineal recipient area had good color, texture, and elasticity, and was not bloated in appearance; linear scars were left in the perineal recipient area and the abdominal donor area without obvious scar hyperplasia or hyperpigmentation; no complications such as incisional rupture, incisional infection, intestinal adhesion, intestinal obstruction, or weakening of the abdominal wall strength occurred in the abdominal donor area, and the abdominal appearance was good with no localized bulge or formation of abdominal hernia; there was no local recurrence of tumor or metastasis in any patient. Conclusions: The surgical approach of using the modified vertical rectus abdominis myocutaneous flap to repair the skin and soft tissue defects after abdominoperineal resection for rectal cancer is relatively simple in operation, can achieve good postoperative appearances of the donor and recipient areas with few complications, and is worthy of clinical promotion.

[Clinical analysis of lung adenocarcinoma with epidermal growth factor receptor mutation transformed into sarcoma].

Objective: To analyze the clinical data of a case of lung adenocarcinoma with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) resistance transforming into sarcoma, and to conduct a literature review to improve the understanding of the resistance mechanism. Histological transformation is a unique form of acquired resistance of EGFR-TKIs in non-small cell lung cancer (NSCLC). Thereinto, the transformation of small cell carcinoma is more common, and the transformation of sarcoma is rarely reported. Methods: Clinicopathological data on the treatment process, pathological features, and clinical outcome of the patient with EGFR-TKIs-resistance lung adenocarcinoma transforming into sarcoma were collected. The literature was reviewed to analyze the pathogenetic mechanism for sarcomatoid carcinoma or sarcoma transformation after drug resistance of adenocarcinoma, as well as the clinical characteristics of the patients and the corresponding therapeutic schemes. Results: We reported a patient with lung adenocarcinoma who developed EGFR-T790M mutation after first-line treatment with icotinib and sarcoma transformation after second-line treatment with almonertinib. Chemotherapy, radioactive particle implantation, antiangiogenic therapy and immunotherapy were followed, but the results were unsatisfactory. There was no report of EGFR-TKIs-resistant lung adenocarcinoma transforming into sarcoma. Among the 14 reports of adenocarcinoma transforming into sarcomatoid carcinoma, 8 cases had EGFR mutation, 3 cases had ALK mutation, 2 cases had ROS1 mutation, and 1 case had no asscoiated sensitive mutation. The median survival of 14 patients with adenocarcinoma transforming to sarcomatoid carcinoma was only 3 months. Conclusions: Sarcoma transformation can be one of the forms of drug resistance in patients with lung adenocarcinoma with EGFR-TKIs. The prognosis of patients with adenocarcinoma after transformation into sarcoma is poor.

Clinicopathological and prognostic significance of PD-L1 and TIM-3 expression in medullary thyroid carcinoma: a retrospective immunohistochemistry study.

PURPOSE: Expression of the programmed death-ligand 1 (PD-L1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in medullary thyroid carcinoma (MTC) has been controversial and rarely reported. METHODS: Surgical specimens of 190 MTC patients who had initial curative-intent surgery were collected. Immunohistochemistry of PD-L1 and TIM-3 was performed using 22C3 pharmDx (Dako, Carpinteria, CA) and anti-TIM-3 (1:500, ab241332, Abcam). Stained slides were scored using a combined positive score (CPS) with a cutoff of ≥ 1. We established correlations between PD-L1 expression, TIM-3 expression, clinicopathological, and survival data. RESULTS: 13 cases (13/190, 6.84%) were positive for PD-L1 expression, and 42 cases (42/154, 27.27%) for TIM-3 expression. PD-L1 expression was correlated to TIM-3 expression (P = 0.002), but was not related to overall survival (OS) or progression-free survival (PFS). TIM-3 expression was correlated to perineural invasion (P = 0.040). Multivariate Cox analysis showed that lymphovascular invasion (LVI) was independently associated with OS. And tumor size, LVI, and lymph node metastases were significantly associated with PFS. Furthermore, the multivariate logistic analysis showed multifocal status, LVI, pathological T stage and lymph node metastasis were independent risk factors for biochemical recurrence/persistent disease. CONCLUSIONS: We demonstrated that PD-L1 and TIM-3 expression were not frequent in MTC and were not associated with survival prognosis. Our results should be considered when clinical trials of PD-L1 or TIM-3 blockades are implemented.

[Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation].

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.