BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Col la can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Co I la group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Col la gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Col la and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP＞5).The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network(pathway impact=0.428 57).(2)Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Col la group had different degrees of damage;the femoral head contour was irregular;the trabeculae in the subchondral bone of the femoral head were missing and disordered,and some cystic structures were visible.Compared with the model group,the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder.Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted,and the empty bone lacuna rate and adipocyte invasion were increased.Compared with the model group,the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced.(3)These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

Neurosyphilis is a group of clinical syndromes caused by treponema pallidum invading the central nervous system and causing varying degrees of damage to the brain parenchyma, brain (spinal) membrane or spinal cord. Cerebral syphilitic gumma is the rarest form of neurosyphilis, and its clinical manifestations lack specificity, which is easily confused with other intracranial space occupying lesions on imaging. In this article, a patient with cognitive dysfunction, intracranial hypertension, and imaging findings similar to multicentric glioma was diagnosed as cerebral syphilitic gumma by serology, cerebrospinal fluid test and brain histopathology. The symptoms basically disappeared after treatment with standard penicillin. This report aims to raise awareness of cerebral syphilitic gumma in order to reduce missed diagnosis and misdiagnosis.

Objective:To investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.Methods:The experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups. Results:① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05). Conclusions:Overactivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.

BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Col la can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Co I la group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Col la gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Col la and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP＞5).The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network(pathway impact=0.428 57).(2)Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Col la group had different degrees of damage;the femoral head contour was irregular;the trabeculae in the subchondral bone of the femoral head were missing and disordered,and some cystic structures were visible.Compared with the model group,the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder.Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted,and the empty bone lacuna rate and adipocyte invasion were increased.Compared with the model group,the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced.(3)These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

Neurosyphilis is a group of clinical syndromes caused by treponema pallidum invading the central nervous system and causing varying degrees of damage to the brain parenchyma, brain (spinal) membrane or spinal cord. Cerebral syphilitic gumma is the rarest form of neurosyphilis, and its clinical manifestations lack specificity, which is easily confused with other intracranial space occupying lesions on imaging. In this article, a patient with cognitive dysfunction, intracranial hypertension, and imaging findings similar to multicentric glioma was diagnosed as cerebral syphilitic gumma by serology, cerebrospinal fluid test and brain histopathology. The symptoms basically disappeared after treatment with standard penicillin. This report aims to raise awareness of cerebral syphilitic gumma in order to reduce missed diagnosis and misdiagnosis.

Objective:To investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.Methods:The experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups. Results:① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05). Conclusions:Overactivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.

Objective:To explore the value of radiomics and deep learning in predicting the efficacy of initial transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods:This was a cohort study. The imaging and clinical information of HCC patients treated with TACE in the Second Affiliated Hospital of Harbin Medical University from January 2015 to January 2021 were collected retrospectively. A total of 265 patients were divided into response group (175 cases) and non-response group (90 cases) according to the modified solid tumor efficacy evaluation criteria (mRECIST) 1 to 2 months after initial TACE. According to the proportion of 8∶2, the patients were randomly divided into training group (212 cases, 140 responders and 72 non-responders) and test set (53 cases, 35 responders and 18 non-responders). Univariate and multivariate logistic regression was used to screen clinical variables and construct a clinical model. The radiomics features were extracted from the preoperative CT images, and radiomics model was constructed after feature dimensionality reduction. Using the deep learning method, three residual network (ResNet) models (ResNet18, ResNet50 and ResNet101) were established, and their effectiveness was compared and integrated to build a deep learning model with best performance. Univariate and multivariate logistic regression was used to combine pairwise three models to establish the combined model. The receiver operating characteristic curve was used to evaluate the performance of the model to distinguish between TACE response and non-response groups.Results:In the test set, the area under the curve (AUC) of the clinical model and the radiomics model in the differentiation between response and non-response after TACE were 0.730 (95% CI 0.569-0.891) and 0.775 (95% CI 0.642-0.907). The AUC of ResNet18, ResNet50 and ResNet101 were 0.719, 0.748 and 0.533, respectively. The AUC for deep learning model obtained by integrating ResNet18 and ResNet50 was 0.806 (95% CI 0.665-0.946). After pairwise fusion, the combined deep learning-radiomics model showed the highest performance, with an AUC of 0.843 (95% CI 0.730-0.956), which was better than those of the deep learning-clinical model (AUC of 0.838, 95% CI 0.719-0.957) and the radiomics-clinical model (AUC of 0.786, 95% CI 0.648-0.898). Conclusions:The combined model of radiomics and deep learning has high performance in predicting the curative effect of TACE in patients with HCC before operation.

BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome