Purpose/Significance To use multimodal data analysis method to mine medical Q&A data in online healthcare platforms and predict whether patients will adopt online doctors'responses.Method/Process First,numerical,categorical,textual,and visual data related to doctor-patient Q&A are obtained from online healthcare platforms,and three datasets of acute disease,chronic disease and mixed disease are constructed according to disease types.Then,normalization,one-hot encoding,Med-BERT,and convolutional neural network are used respectively to process numerical,categorical,textual,and visual data.Finally,a gradient boosting decision tree is used to predict whether patients will adopt online doctors'responses.Result/Conclusion Doctors'profile pictures can improve the prediction effect of online doctor response adoption,and multimodal data mining can effectively predict the response adoption.

Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Objective To explore the application value of polidocanol foam combined with absolute ethanol in the treatment of lower extremity venous malformation(VM)in children.Methods The clinical data of 20 children with lower extremity VM were analyzed retrospectively.All of these children were diagnosed with VM of lower extremity by MRI and were treated with digital subtraction angiography(DSA)guided percutaneous sclerotherapy.Different hardening agents were selected according to the classification,the size of the lesion range and the flow rate during the operation.The VM with small lesions range,shallow location and slower velocity were treated with polidocanol foam only,while the VM with larger lesion range and faster velocity were combined treated with abso-lute ethanol.Clinical symptoms and MRI were used to evaluate the curative effect one month after operation.Results Twenty chil-dren received sclerotherapy.After the treatment,15 cases were cured,3 cases showed significantly effective,and 2 cases were effec-tive.Some of the children had pain and swelling of different degrees within 48 hours after operation,who were given symptomatic treatment,and the symptoms disappeared in the short time.The skin of the lesion ulcerated in one case and the ulceration healed after treatment.Conclusion Polidocanol foam combined with absolute ethanol is safe and effective in the treatment of lower extremity VM in children,and the combination can improve the curative effect and reduce the occurrence of postoperative complications.

Objective To explore the clinical application value of interventional embolization in the treatment of giant infant parotid hemangioma.Methods The clinical data of 17 cases of giant infant parotid hemangioma were analyzed retrospectively.All childrens were performed relevant preoperative examination and CT enhancement examination,with no absolute contraindications for the treat-ment.Interventional embolization was performed under static aspiration compound anesthesia,propranolol was given orally on the same postoperative day.One month after surgery,the clinical effect was evaluated according to the clinical symptoms and ultrasound examination.Results A total of 18 interventional embolization were performed on 17 childrens,who were followed up for 6 months after surgery.The tumor body shrank by more than 80％,after treatment,the child had a symmetrical facial face,no soft tissue rupture,and normal skin color with no impairment of the parotid gland and facial nerve function.Conclusion Interventional embolization is safe and effective in the treatment of giant infant parotid hemangioma,and can become one of the preferred treatment methods for giant infant parotid hemangioma.

Objective To explore the efficacy and safety of TACE combined with propranolol for treating giant infantile hepatic hemangioma(IHH).Methods Ten infants with giant IHH who underwent TACE combined with propranolol were retrospectively enrolled.The technical success rate,complications and recurrence were recorded.The therapeutic effect was evaluated according to clinical symptoms and changes of IHH volume before and 6 months after TACE.Results Totally 15 times of TACE were successfully performed in 10 infants,with technical success rate of 100%.Bleomycin-lipiodol emulsion+poly(vinyl alcohol)(PVA)+coil embolization were performed in 3 cases,while bleomycin-lipiodol emulsion+PVA embolization were performed in 7 cases.Complications of TACE included subcutaneous hematoma around the puncture site in 1 case and transient hypothermia within 24 h after TACE in 2 cases,all alleviated after symptomatic treatments.No other complication occurred.Six months after the last TACE,significantly effective was observed in 9 cases(9/10,90.00%),while effective was noticed in 1 case(1/10,10.00%),with total therapeutic effective rate of 100%.No serious complication such as gallbladder necrosis,liver necrosis,death,nor recurrence of hepatic hemangioma occurred during follow-up.Conclusion TACE combined with propranolol was effective and safe for treating giant IHH.

Objective:To explore the locations of the lumbosacral nerve roots by use of the magnetic stimulation.Methods:Thirty healthy subjects were studied. The projections of the right L 2 to S 1 intervertebral foramina on their body surfaces were determined manually with ultrasound assistance. Magnetic stimulation was applied to different nerve root segments to induce compound muscle action potentials (CMAP) in the vastus medialis, tibialis anterior, and gastrocnemius muscles of the lower limbs. The changes in latency, amplitude, and motor threshold were observed. Results:Magnetic stimulation on the L 2-L 3 segment resulted in a significant direct excitation of the vastus medialis. That on the L 5-S 1 segment evoked a significant direct excitatory effect on the tibialis anterior and gastrocnemius, with a motor threshold below 40%, an amplitude exceeding 1mV, and many effective responses. However, during the magnetic stimulation on the L 4 segment, the amplitude of the vastus medialis was above 1mV, with no significant differences in the number of effective responses among the muscle groups. Moreover, there was a stepwise change in the latency of effective muscle responses to magnetic stimulation at different segments. The CMAP latencies of 12+ ms for the tibialis anterior and 13+ ms for the gastrocnemius indicated activation of the L 5 and L 4 nerve roots, respectively, while those of 6+ ms, 7+ ms, and 8+ ms for the vastus medialis suggested activation of the L 4, L 3, and L 2 nerve roots, respectively. Conclusions:Based on the responses (CMAP latency, amplitude and motor threshold) of the vastus medialis, tibialis anterior and gastrocnemius to magnetic stimulation at different L 2 to S 1 segments, the spinal nerve root segments responsible for innervation can be inferred.

Humans ; Prognosis ; Multiple Myeloma/diagnosis* ; Neoplasm Staging ; Hematopoietic Stem Cell Transplantation ; Patients ; Retrospective Studies

OBJECTIVE: To investigate the effectiveness of sequential plate internal fixation in the correction of Madelung deformity after ulnar osteotomy and shortening. METHODS: The clinical data of 13 patients with Madelung deformity admitted between September 2015 and July 2021 were retrospectively analyzed. There were 5 males and 8 females with an average age of 18.3 years ranging from 17 to 23 years. The disease duration ranged from 12 to 24 months, with an average of 17 months. Three cases had a clear history of trauma. All patients had external radial deviation deformity and limited movement of the ulnar deviation, and the ulnar impact pain was significant during ulnar deviation movement; 9 patients had limited wrist joint supination movement, and the supination movement was normal. In the first stage, ulnar osteotomy and shortening combined with external fixator were used to correct wrist deformity in 13 patients. After operation, bone transfer was performed 6 times per day, with adjustments made every 4 hours, which was 1 mm per day. After the osteotomy was in place, the ulnar plate internal fixation was performed to reconstruct the ulnar stability in the second stage. The Cooney wrist joint score was used to assess the pain, function, range of motion, flexion and extension range of motion, and grip strength of the wrist joint before operation and before the removal of internal fixator. The subjective feeling and appearance satisfaction of patients were recorded. RESULTS: After the second-stage operation, all the 13 patients were followed up 10-22 months, with an average of 15 months. The deformity of wrist joint disappeared after operation, and the flexion, extension, and ulnar deviation were basically normal. There was no complication such as ulnar impingement sign, nonunion or infection. Wrist function, pain, and range of motion were significantly improved after operation, except for 1 patient who had no significant improvement in rotation and pain. The ulnar internal fixator was removed at 10-18 months after the second-stage operation. The scores of pain, function, range of motion, flexion and extension range of motion, and grip strength in the Cooney wrist score before removal of internal fixator significantly improved when compared with those before operation ( P<0.05). Subjective and appearance satisfaction of patients were excellent in 9 cases, good in 3 cases, and fair in 1 case. CONCLUSION Ulnar osteotomy and shortening with sequential plate internal fixation for correction of Madelung deformity, with mild postoperative pain, can effectively avoid bone nonunion, improve wrist joint function, and have significant effectiveness.
Male ; Female ; Humans ; Adolescent ; Retrospective Studies ; Ulna/surgery* ; Osteochondrodysplasias ; Radius Fractures/surgery* ; Wrist Joint/surgery* ; Osteotomy ; Range of Motion, Articular ; Treatment Outcome

BACKGROUND: Hyaluronic acid dermal fillers are composed of cross-linked viscoelastic particles with high biocompatibility. The performance of the fillers is determined by the viscoelastic properties of particles and the connecting force between particles. However, the relationships among the properties of fillers, the interaction of the gels and the surrounding tissue are not clear enough.METHOD: Four kinds of typical dermal filler were selected in this research to reveal the interaction between the gels and cells. A series of analytical tools was applied to characterize the structure and physicochemical properties of the gel, as well as observing their interaction with the surrounding tissues in vivo and discussing their internal mechanism.RESULT: The large particles internal the gel and the high rheological properties endow the Restylane2 with excellent support. However, these large-size particles have a significant impact on the metabolism of the local tissue surrounding the gel. Juvéderm3 present gel integrity with the high cohesiveness and superior support. The rational matching of large and small particles provides the Juvéderm3 with supporting capacity and excellent biological performance. Ifresh is characterized by small-size particles, moderate cohesiveness, good integrity, lower viscoelasticity and the superior cellular activity located the surrounding tissues. Cryohyaluron has high cohesion and medium particle size and it is prominent in cell behaviors involving localized tissues. Specific macroporous structure in the gel may facilitate the nutrients delivering and removing the waste. CONCLUSION It’s necessary to make the filler both sufficient support and biocompatibility through the rational matching of particle sizes and rheological properties. Gels with macroporous structured particle showed an advantage in this area by providing a space inside the particle.