Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective:To develop and validate a nomogram model for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on preoperative enhanced computed tomography imaging features and clinical data.Methods:The clinical data of 210 patients with HCC undergoing surgery in the Second Affiliated Hospital of Anhui Medical University from May 2018 to May 2022 were retrospectively analyzed, including 172 males and 38 females, aged (59±10) years old. Patients were randomly divided into the training group ( n=147) and validation group ( n=63) by systematic sampling at a ratio of 7∶3. Preoperative enhanced computed tomography imaging features and clinical data of the patients were collected. Logistic regression was conducted to analyze the risk factors for HCC with MVI, and a nomogram model containing the risk factors was established and validated. The diagnostic efficacy of predicting MVI status in patients with HCC was assessed by receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) of the subjects in the training and validation groups. Results:The results of multifactorial analysis showed that alpha fetoprotein ≥400 μg/ml, intra-tumor necrosis, tumor length diameter ≥3 cm, unclear tumor border, and subfoci around the tumor were independent risk factors predicting MVI in HCC. A nomogram model was established based on the above factors, in which the area under the curve (AUC) of ROC were 0.866 (95% CI: 0.807-0.924) and 0.834 (95% CI: 0.729-0.939) in the training and validation groups, respectively. The DCA results showed that the predictive model thresholds when the net return is >0 ranging from 7% to 93% and 12% to 87% in the training and validation groups, respectively. The CIC results showed that the group of patients with predictive MVI by the nomogram model are highly matched with the group of patients with confirmed MVI. Conclusion:The nomogram model based on the imaging features and clinical data could predict the MVI in HCC patients prior to surgery.

Long non-coding RNA (lncRNA) is a type of non-coding RNA with the more than 200 nucleotides. Several lncRNAs have been identified as the potential targets for cancer therapy. LncRNA00067110 is one of the differentially expressed genes in the transcriptome profiles of melanoma B16-F10 cells compared to normal mice melanocytes. To investigate whether lncRNA00067110 regulates the proliferation, apoptosis and melanogenesis of B16-F10 cells, the calcium-binding tyrosine phosphorylation regulated protein (Cabyr) target gene was predicted by LncTar and verified by dual luciferase activities. The regulating function of lncRNA00067110 was investigated by the analysis of transcriptome profiles and to detect the proliferation, apoptosis and melanin production of B16-F10 cells transfected by the overexpression plasmids of lncRNA00067110. The results showed that the relationship of lncRNA00067110 targeting Cabyr, the mRNA and protein levels of proliferation (MEK/ERK/MNK/CREB) and melanogenesis-related genes (TYR family and CREB) were significantly down-regulated, while the mRNA and protein levels of apoptosis-related genes (AKT and Bcl-2) were up-regulated in B16-F10 cells with lncRNA00067110 overexpression. The transcriptome profile of B16-F10 cells with lncRNA00067110 overexpression showed that 17 genes were differentially expressed, among which Cabyr was up-regulated. Furthermore, the effect of lncRNA00067110 on the phenotypes of cell proliferation and apoptosis were verified. The results suggested that lncRNA00067110 might be a novel target for the treatment of melanoma by targeting Cabyr, which regulate the expression of related genes to inhibit the proliferation and melanogenesis, as well as to induce the apoptosis of B16-F10 cells.

The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1β, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.
Animals ; Aporphines ; Diet, High-Fat/adverse effects* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/genetics*

OBJECTIVE: To study effects of postoperative regular training of core muscle strength guided by the concept of enhanced recovery after surgery (ERAS) on the rehabilitation of elderly patients with osteoporotic lumbar vertebral compression fracture after vertebroplasty (PVP) and kyphoplasty(PKP). METHODS: Ninety-four elderly patients with osteoporotic lumbar compression fractures who underwent PKP or PVP from January 2016 to January 2018 and met inclusion criteria were divided into observation group and control group. All the patients were treated with routine anti osteoporosis therapy after operation. There were 47 patients in the observationgroup, including 18 males and 29 females, with an average age of (62.62±3.21) years old;in the control group, there were 47 cases, including 17 males and 30 females, with an average age of (62.38±2.84) years old. The patients in the control group were trained by traditional way, and the patients in observation group were instructed to conduct regular training of core muscle strength according to ERAS concept. The patients were followed up for 1, 3 and 6 months after operation. Patients' conditions were quantitatively evaluated according to Barthel scale, JOA low back pain score and Oswestry Disability Index, and the differences in treatment effects between two groups were statistically analyzed and compared. RESULTS: All the patients were followed up, and the Barthel scale, JOA low back pain score and Oswestry Disability Index score of the observation group were all better than those of the control group on the 1st and the 3rd months after surgery( CONCLUSION Early regular core strength training has a positive effect on early functional recovery and improvement of life ability after PKP or PVP for elderly patients with osteoporotic lumbar compression fractures, which is in line with the concept of accelerated rehabilitation surgery.
Aged ; Enhanced Recovery After Surgery ; Female ; Fractures, Compression/surgery* ; Humans ; Kyphoplasty ; Male ; Middle Aged ; Osteoporotic Fractures/surgery* ; Spinal Fractures/surgery* ; Treatment Outcome ; Vertebroplasty

Objective:To investigate the clinicopathological characteristics of primary gastrointestinal stromal tumors (GIST) with PDGFRα mutation and analyze the prognosis of different subtypes.Methods:From Jun 2010 to Jun 2019, the clinicopathological data of 35 patients with primary PDGFRα mutation GIST, who underwent surgical therapy in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were analyzed retrospectively.Results:The main symptoms was abdominal pain (28 cases, 80%), followed by abdominal mass (6 cases, 17%), and hemafecia (1 case, 3%). 31 primary lesions (89%) were located in the stomach and 4 (11%) in other than stomach. 13 cases (37%) were of epithelioid cells, 14 cases (40%) were of spindle cells and 8 cases (23%) were of mixed cells. 27 cases (77%) were CD117 positive , 28 cases (80%) CD34 positive , and 30 cases (86%) were DOG-1 positive. 19 cases (54%) had D842V mutation and 16 cases (46%) had non-D842V mutation. Complete surgical resection was performed in all patients, with no perioperative death. The 3-year recurrence-free survival rate of the D842V mutation group was lower than that of the non-D842V mutation group (84% vs. 100%, P=0.045). Conclusions:The mutation rate of PDGFRα gene was low, mostly derived from the stomach. PDGFRα mutation GIST presents inert biological behavior and the overall prognosis was good.

OBJECTIVE: From the perspective of clinical application to analyze the effectiveness and reliability of CPC/PMMA bone cement in percutaneous kyphoplasty (PKP) for the treatment of elderly patients with osteoporotic thoracolumbar fractures. METHODS: A retrospective analysis was performed on 62 patients with osteoporotic compression fracture of single-vertebral thoracic or lumbar segment who underwent PKP surgery and had a bone density less than or equal to -3.0 SD from February 2016 to December 2016. Among them, 23 patients were in CPC/PMMA group, with an average age of (77.6±2.2) years old, 39 patients in PMMA group, with an average age of (77.1±1.1) years old. The indexes between two groups were compared, including the visual analogue scale (VAS), height ratio of anterior vertebra (AVHR), local Cobb angle, cement leakage, new adjacent vertebral fracture(NAVF). RESULTS: There were no significant difference in gender, age, follow-up time and preoperative VAS, AVHR, local Cobb angle between two groups (>0.05), at the 1 day after operation, VAS, AVHR, local Cobb angle in all patients got obvious improvement (<0.05), which was no significant difference at 1 day after operation and final follow-up (>0.05). At the same time, there was no statistically significant difference in the incidence of new adjacent vertebral fracture and cement leakage (>0.05). The pain in both groups continued to improve at follow up after operation (<0.05), the local Cobb angle increased (<0.05) and AVHR decreased slightly (<0.05). However, the images of conventional methods (X-ray or CT) could not find signs about CPC degeneration and new bone ingrowth. CONCLUSION CPC/PMMA composite bone cement is safe and reliablein PKP for treatment of elderly patients with osteoporotic thoracolumbar fractures, which can effectively relieve pain and maintain vertebral body stability. It has the same curative effect as PMMA bone cement. It was worthy to research more in future, although no direct evidences support the CPC/PMMA composite bone cement can reduce the incidence of adjacent vertebral fracture, CPC degeneration or new bone ingrowth.
Aged ; Bone Cements ; Dinucleoside Phosphates ; Fractures, Compression ; Humans ; Kyphoplasty ; Osteoporotic Fractures ; Polymethyl Methacrylate ; Reproducibility of Results ; Retrospective Studies ; Spinal Fractures ; Treatment Outcome ; Vertebroplasty

Objective:To explore the feasibility and clinical efficacy of gelatin sponge packing in reducing bone cement leakage in percutaneous kyphoplasty (PKP).Methods:A retrospective case-control study was conducted in data of 171 patients (171 vertebrae) with monosegmental lumbar osteoporosis compressive fracture treated by PKP from January 2015 to December 2018 in Sichuan Orthopedic Hospital. There were 66 males and 105 females, with the age of (67.9±6.7)years (range, 60-87 years). There were 22 patients with T 10 fracture, 28 with T 11 fracture, 37 with T 12 fracture, 34 with L 1 fracture, 32 with L 2 fracture and 18 with L 3 fracture. A total of 80 patients were pre-filled with gelatin sponge before injection (Group A), and 91 patients were not filled with gelatin sponge before injection (Group B). The operation time, amount of bone cement, and rate of bone cement leakage were recorded. The change of anterior vertebral height, Cobb angle, visual simulation score (VAS) and Oswestry disability index (ODI) were compared before operation and at postoperative 1 day, 3 months, 6 months, 12 months. Results:All patients were followed up for 1-12 months [(12.8±0.6)months]. The operation time in Group A and B was (48.3±1.2)minutes and (42.3±1.3)minutes ( P<0.05). The amount of bone cement in Group A and B was (5.4±0.8)ml and (5.6±0.7)ml ( P>0.05). The incidence of bone cement leakage in Group A and B was 11% (9/80) and 26% (24/91) ( P<0.05). There was no significant difference between the two groups in the anterior height of injured vertebrae, change of Cobb angle, VAS and ODI before and after operation ( P>0.05). Conclusion:Gelatin sponge can reduce the rate of bone cement leakage in PKP for the treatment of thoracolumbar osteoporosis compressive fracture, and has similar effect with PKP in correcting kyphosis, alleviating pain and improving life quality.

Objective:At present, the modified NIH classification commonly used in clinical practice is still insufficient for assessing the risk of postoperative recurrence in some patients with intermediate-high risk gastrointestinal stromal tumors (GIST). Through exploring risk factors for recurrence of intermediate-high risk GIST, this study establishes a predictive model for recurrence with more convenience and more precision in order to guide adjuvant therapy for intermediate-high risk GIST patients.Methods:A retrospective case-control study was carried out. Clinical and pathological data of 432 GIST patients who did not receive preoperative targeted treatment, underwent complete resection in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2005 to June 2018, and were diagnosed as intermediate- or high-risk based on modified NIH classification by postopertive pathology, were retrospectively analyzed. Cox regression model was used to idenitify independent risk factors of recurrence, and a recurrence risk scoring model was established. The receiver operating characteristic curve (ROC curve), consistency index (C-index) and calibration curve were used to evaluate the accuracy of the scoring model in predicting the recurrence of moderate-risk and high-risk GIST patients.Results:Among 432 GIST patients, 332 were diagnosed as high-risk and 100 as moderate-risk; 237 were males and 195 females with average age of (57.4±12.4) years. Of 432 patients, 211 cases (48.8%) had fibrinogen (FIB) >3.5 g/L; 85 cases (19.7%) had platelet to lymphocyte ratio (PLR)>272.5; 122 cases (28.2%) had neutrophil to lymphocyte ratio (NLR) > 4.2; 102 cases (23.6%) had systemic inflammatory reaction index (SIRI)> 2.7; 198 cases (45.8%) had tumor long diameter >8 cm and 108 cases (25.0%) had mitotic counts > 8/50 HPF. Cox multivariable analysis showed that FIB (HR=1.789, 95% CI: 1.058-3.027, P=0.030), PLR (HR=1.862, 95% CI: 1.067-3.249, P=0.029), SIRI (HR=1.790, 95% CI: 1.039-3.084, P=0.036), tumor long diameter (HR=1.970, 95% CI: 1.105-2.925, P=0.017) and mitotic counts (HR=2.187, 95% CI:1.211-3.950, P=0.009) were independent risk factors for recurrence in patients with middle-risk and high-risk GIST. These 5 factors were included in the risk scoring model, which was given a weight score of 58 points, 62 points, 58 points, 63 points, and 78 points, respectively. Patients with a total score of ≤ 78 points were classified as moderate-risk recurrence (group I), those of 78 to 136 points as high-risk recurrence (group II) and those of >136 points as very high-risk recurrence (group III). ROC curve showed that the area under the curve (AUC) of the scoring model was 0.730 and the C-index was 0.724 (95% CI:0.687-0.787). The calibration curves and the Kaplan-Meier curves of patients in the three groups revealed that this model had a good predictive accuracy. Conclusions:For intermediate-risk and high-risk GIST patients, the preoperative FIB >3.5 g/L, PLR > 272.5 and SIRI > 2.7 are independent risk factors of recurrence after surgery. The recurrence risk scoring model established by combining tumor long diameter, mitotic counts, FIB, PLR and SIRI can effectively predict the risk of postoperative recurrence and metastasis in moderate-risk and high-risk GIST patients.