Computer-aided design to enhance the stability of aldo-keto reductase KdAKR.

The aldo-keto reductase (AKR) KdAKR from Kluyvermyces dobzhanskii can reduce t-butyl 6-chloro-(5S)-hydroxy-3-oxohexanoate ((5S)-CHOH) to t-butyl 6-chloro-(3R,5S)-dihydroxyhexanoate ((3R,5S)-CDHH), which is the key chiral intermediate of rosuvastatin. Herein, a computer-aided design that combined the use of PROSS platform and consensus design was employed to improve the stability of a previously constructed mutant KdAKRM6 . Experimental verification revealed that S196C, T232A, V264I and V45L produced improved thermostability and activity. The "best" mutant KdAKRM10 (KdAKRM6 -S196C/T232A/V264I/V45L) was constructed by combining the four beneficial mutations, which displayed enhanced thermostability. Its T50 15 and Tm values were increased by 10.2 and 10.0°C, respectively, and half-life (t1/2 ) at 40°C was increased by 17.6 h. Additionally, KdAKRM10 demonstrated improved resistance to organic solvents compared to that of KdAKRM6 . Structural analysis revealed that the increased number of hydrogen bonds and stabilized hydrophobic core contributed to the rigidity of KdAKRM10 , thus improving its stability. The results validated the feasibility of the computer-aided design strategy in improving the stability of AKRs.

Antinociceptive iridoid glycosides from the aerial parts of Paederia foetida.

Two previously undescribed iridoid glycosides, 6'-O-trans-feruloyl-(4S,6R)-3,4-dihydro-3ß-ethoxypaederoside (1) and 6'-O-trans-caffeoyl-(4S,6R)-3,4-dihydro-2'-O-3α-paederoside (2), were isolated from the 90% EtOH extract of the air dried aerial parts of Paederia Foetida. Structural elucidation of all the compounds was performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. The two isolated iridoid glycosides were tested in vivo for their antinociceptive properties. As a result, 2 showed potent antinociceptive effect and its ID50 value (53.4 µmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.

Outcomes of Salvage Surgery Versus Non-Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma After Conversion Therapy with Transcatheter Arterial Chemoembolization Combined with Lenvatinib Plus Anti-PD-1 Antibody: A Multicenter Retrospective Study.

BACKGROUND: Combination treatment with transcatheter arterial chemoembolization (TACE), lenvatinib, and anti-programmed death-1 (anti-PD-1) antibodies (triple therapy) has a high rate of tumor response and converted resection for initially unresectable hepatocellular carcinoma (uHCC) patients. This study aimed to assess the outcomes of salvage surgery in uHCC patients after conversion therapy with triple therapy. METHODS: uHCC patients who met the criteria for hepatectomy after receiving triple therapy as first-line treatment were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) rates in patients who received salvage surgery (SR group) and those who did not (non-SR group) were compared. RESULTS: Of the 144 patients assessed, 91 patients underwent salvage surgery and 53 did not. The OS rates in the SR group were significantly better than those in the non-SR group. The 1- and 2-year OS rates in the SR group were 92.0% and 79.9%, respectively, whereas those in the non-SR group were 85.5% and 39.6 %, respectively (p = 0.007); however, there was no significant difference in the PFS rates. Upon further stratification, OS and PFS were significantly better in the SR group than in the non-SR group in patients who were assessed as partial responses (PR), while there was no significant difference in patients who were assessed as complete response (CR). CONCLUSIONS: Salvage surgery is recommended and is associated with a favorable prognosis for uHCC patients who were assessed as PR after conversion therapy, however it may not be necessary for uHCC if CR was achieved.

Transcatheter arterial chemoembolisation combined with lenvatinib plus camrelizumab as conversion therapy for unresectable hepatocellular carcinoma: a single-arm, multicentre, prospective study.

Background: The synergistic effect of locoregional therapy in combination with systemic therapy as a conversion therapy for unresectable hepatocellular carcinoma (uHCC) is unclear. The purpose of this study was to evaluate the efficacy and safety of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and camrelizumab (TACE + LEN + CAM) as conversion therapy for uHCC. Methods: This single-arm, multicentre, prospective study was conducted at nine hospitals in China. Patients (aged 18-75 years) diagnosed with uHCC, an Eastern Cooperative Oncology Group performance score (ECOG-PS) of 0-1 and Child-Pugh class A received camrelizumab (200 mg, every 3 weeks) and lenvatinib (bodyweight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day) after TACE treatment. Surgery was performed after tumour was assessed as meeting the criteria for resection. Patients who did not meet the criteria for surgery continued to receive triple therapy until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR) according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and safety. Secondary endpoints included the surgical conversion rate, radical (R0) resection rate, and disease control rate (DCR). This study was registered with Chinese Clinical Trial Registry (ChiCTR2100050410). Findings: Between Oct 25, 2021, and July 20, 2022, 55 patients were enrolled. As of the data cutoff on June 1, 2023, the median follow-up was 13.3 months (IQR 10.6-15.9 months). The best tumour response to triple therapy was complete response (CR) in 9 (16.4%) patients, partial response (PR) in 33 (60.0%) patients, stable disease (SD) in 5 (9.1%) patients, or progressive disease (PD) in 7 (12.7%) patients. The ORR was 76.4% (42/55, 95% CI, 65.2-87.6%), and the DCR was 85.5% (47/55, 95% CI, 76.2-94.8%) per mRECIST. Twenty-four (43.6%) of the 55 patients suffered from grade 3-4 treatment-related adverse events (TRAEs). No grade 5 TRAEs occurred. A total of 30 (30/55, 54.5%) patients were converted to resectable HCC and 29 (29/55, 52.7%) patients underwent resection. The R0 resection rate was 96.6% (28/29). The major pathologic response (MPR) and pathologic complete response (pCR) rates in the surgery population were 65.5% (19/29) and 20.7% (6/29), respectively. Only one patient developed a Clavien-Dindo IIIa complication (abdominal infection). No Clavien-Dindo IIIb-V complications occurred. The median OS and median PFS were not reached. Interpretation: The triple therapy (TACE + LEN + CAM) is promising active for uHCC with a manageable safety. Moreover, triple therapy has good conversion efficiency and the surgery after conversion therapy is feasible and safe. To elucidate whether patients with uHCC accepting surgical treatment after the triple therapy can achieve better survival benefits than those who receive triple therapy only, well-designed randomised controlled trials are needed. Funding: This study was funded by the Natural Science Foundation of Fujian Province, China (2022J01691) and the Youth Foundation of Fujian Province Health Science and Technology Project, China (2022QNA035).

Outcomes of Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma Converted by Transcatheter Arterial Chemoembolization Combined with Lenvatinib plus Anti-PD-1 Antibodies: A Multicenter Retrospective Study.

Introduction: The actual rate of conversion surgery and its prognostic advantages remain unclear. This study aimed to assess the outcomes of salvage surgery after conversion therapy with triple therapy (transcatheter arterial chemoembolization [TACE] combined with lenvatinib plus anti-PD-1 antibodies) in patients with initially unresectable hepatocellular carcinoma (uHCC). Methods: Patients with initially uHCC who received at least one cycle of first-line triple therapy and salvage surgery at five major cancer centers in China were included. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) rates after salvage surgery. The secondary endpoints were perioperative complications, 90-day mortality, and pathological tumor response. Results: Between June 2018 and December 2021, 70 patients diagnosed with uHCC who underwent triple therapy and salvage surgery were analyzed: 39 with Barcelona Clinic Liver Cancer (BCLC) stage C, 22 with BCLC stage B, and 9 with BCLC stage A disease. The median interval between the start of triple therapy and salvage surgery was 4.3 months (range, 1.7-14.2 months). Pathological complete response and major pathological response were observed in 29 (41.4%) and 59 (84.3%) patients, respectively. There were 2 cases of perioperative mortality (4.3%) and 5 cases of severe perioperative complications (7.1%). With a median follow-up of 12.9 months after surgery (range, 0.3-36.8 months), the median OS and RFS were not reached. The 1- and 2-year OS rates were 97.1% and 94.4%, respectively, and the corresponding RFS rates were 68.9% and 54.4%, respectively. Conclusion: First-line combination of TACE, lenvatinib, and anti-PD-1 antibodies provides a better chance of conversion therapy in patients with initially uHCC. Furthermore, salvage surgery after conversion therapy is effective and safe and has the potential to provide excellent long-term survival benefits.

The changes of neuroactivity of Tui Na (Chinese massage) at Hegu acupoint on sensorimotor cortex in stroke patients with upper limb motor dysfunction: a fNIRS study.

BACKGROUND: Tui Na (Chinese massage) is a relatively simple, inexpensive, and non-invasive intervention, and has been used to treat stroke patients for many years in China. Tui Na acts on specific parts of the body which are called meridians and acupoints to achieve the role of treating diseases. Yet the underlying neural mechanism associated with Tui Na is not clear due to the lack of detection methods. OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) was used to explore the changes of sensorimotor cortical neural activity in patients with upper limb motor dysfunction of stroke and healthy control groups during Tui Na Hegu Point. METHODS: Ten patients with unilateral upper limb motor dysfunction after stroke and eight healthy subjects received Tui Na. fNIRS was used to record the hemodynamic data in the sensorimotor cortex and the changes in blood flow were calculated based on oxygenated hemoglobin (Oxy-Hb), the task session involved repetitive Tui Na on Hegu acupoint, using a block design [six cycles: rest (20 seconds); Tui Na (20 seconds); rest (30 seconds)]. The changes in neural activity in sensorimotor cortex could be inferred according to the principle of neurovascular coupling, and the number of activated channels in the bilateral hemisphere was used to calculate the lateralization index. RESULT: 1. For hemodynamic response induced by Hegu acupoint Tui Na, a dominant increase in the contralesional primary sensorimotor cortex during Hegu point Tui Na of the less affected arm in stroke patients was observed, as well as that in healthy controls, while this contralateral pattern was absent during Hegu point Tui Na of the affected arm in stroke patients. 2. Concerning the lateralization index in stroke patients, a significant difference was observed between lateralization index values for the affected arm and the less affected arm (P < 0.05). Wilcoxon tests showed a significant difference between lateralization index values for the affected arm in stroke patients and lateralization index values for the dominant upper limb in healthy controls (P < 0.05), and no significant difference between lateralization index values for the less affected arm in stroke patients and that in healthy controls (P = 0.36). CONCLUSION: The combination of Tui Na and fNIRS has the potential to reflect the functional status of sensorimotor neural circuits. The changes of neuroactivity in the sensorimotor cortex when Tui Na Hegu acupoint indicate that there is a certain correlation between acupoints in traditional Chinese medicine and neural circuits.

Study protocol of a randomized controlled trial for the synergizing effects of rTMS and Tui Na on upper limb motor function and cortical activity in ischemic stroke.

Upper limb motor dysfunction after stroke is a serious threat to the living quality of patients and their families. Recovery of upper limb motor function after stroke largely relies on the activation and remodeling of neural circuits. rTMS (repetitive transcranial magnetic stimulation) has been proved to promote the reconstruction of neural synapses and neural circuits. However, there are still a large number of patients who cannot fully recover and leave behind varying degrees of dysfunction. Considering the systemic pathology after stroke, in addition to focal brain injury, stroke can also cause extensive dysfunction of peripheral organs. The rehabilitation strategy for stroke should combine the treatment of primary brain lesions with the intervention of secondary systemic damage. The aim of this trial is to verify the efficacy of rTMS synergize with Tui Na (Chinese Massage) on upper limb motor function after ischemic stroke, and to explore the mechanism of activation and remodeling of sensorimotor neural circuits with functional near-infrared spectroscopy. Ninety patients will be randomly assigned to either rTMS + Tui Na + conventional rehabilitation group (the experimental group) or rTMS + conventional rehabilitation group (the control group) in 1:1 ratio. Intervention is conducted five sessions a week, with a total of twenty sessions. The primary outcome is Fugl-Meyer Assessment, and the secondary outcomes include Muscle Strength, Modified Ashworth Assessment, Modified Barthel Index Assessment, motor evoked potentials and functional near-infrared spectroscopy. There are four time points for the evaluation, including baseline, 2 weeks and 4 weeks after the start of treatment, and 4 weeks after the end of treatment. This study is a randomized controlled trial. This study was approved by Institutional Ethics Committee of Shanghai Third Rehabilitation Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (approval No. SH3RH-2021-EC-012) on December, 16th, 2021. The protocol was registered with Chinese Clinical Trial Registry (ChiCTR2200056266), on February 3th, 2022. Patient recruitment was initiated on February 10th, 2022, and the study will be continued until December 2023.

Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence: A multicenter retrospective study.

Background: Early recurrence is common after surgical resection (SR) for hepatocellular carcinoma (HCC) with high risk of recurrence and is associated with poor prognosis. The combinations of lenvatinib (LEN), anti-PD-1 antibodies (PD-1) and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. It is unknown whether triple therapy for neoadjuvant treatment of resectable HCC with high risk of recurrence is effective. This article aimed to compare the outcomes of surgery alone and neoadjuvant combination treatment with triple therapy before SR in patients with HCC with high risk of recurrence. Methods: A retrospective study was conducted on patients diagnosed with HCC with high risk of recurrence who received treatment with or without triple therapy. The records of 24 patients in the triple therapy group and 76 patients in the surgery-alone group were analyzed. Propensity score matching (PSM) was performed to minimize the influence of potential confounders. Results: One hundred patients were enrolled. In the triple therapy group, 8 (33.3%) and 12 (50.0%) patients had complete and partial responses, respectively, as assessed by an investigator. Before PSM, the overall survival (OS) rates for the triple therapy group at 6, 12, 18, and 24 months were 100.0%, 100.0%, 100.0%, and 85.7%, respectively, compared with corresponding 92.1%, 73.7%, 53.9%, and 48.7% for the surgery-alone group (P<0.001). The disease-free survival (DFS) rates were 82.2%, 66.95%, 48.8%, and 48.8% for the triple therapy and 41.92%, 28.34%, 27.05%, and 22.99% for the surgery-alone group (P=0.003). After PSM, DFS and OS were significantly longer in the triple therapy group than in the surgery-alone group (DFS, p=0.019; OS, p=0.003). Conclusions: Neoadjuvant combination treatment before SR had a high rate of tumor response and provided significantly better postoperative survival outcomes than surgery alone in patients with HCC with high risk of recurrence.

Multifunctional Ionic Fullerene Additive for Synergistic Boundary and Defect Healing of Tin Perovskite to Achieve High-Efficiency Solar Cells.

A series of new ionic fullerene derivatives (C60-RNH3-X; X = Cl, Br, or I) were designed especially for using as additives for tin perosvkite (TPsk, with chemical formula of FA0.98EDA0.01SnI3) to form TPsk-C60-RNH3-X bulk heterojunction (BHJ) films. Inverted tin-perovskite solar cells (TPSCs) based on BHJ TPsk-C60-RNH3-Br absorber achieved the highest power conversion efficiency up to 11.74% with very high FF of 73%, without current hysteresis and stable in a glovebox. The designed spherical ionic fullerene halide additive, sitting in the grain boundaries of the TPsk film, can not only improve the quality of the TPsk film and change the valence band energy to match better with the PEDOT:PSS hole transporter but also be a carrier transporting connector between tin-perovskite grains, the defects/traps passivation/healing agent by interacting with Sn2+ ions and filling the halogen vacancies. The functions of the ionic fullerene halide additive were revealed with XRD patterns, SEM images, element mapping, UPS spectra, infrared spectra, AFM, and SCLC data. Being able to passivate newly generated defects during device operation or sitting on the shelf is an important step to improve the long-term stability of TPSCs. If a passivation agent can move dynamically during cell operation or storage to heal the defects of perovskite, the instability problem of TPSCs can be alleviated. The spherical ionic fullerene halide could be one of the ideal passivation agents satisfying this purpose.

[The distribution of Mas-related G protein-coupled receptor A in cerebrospinal fluid-contacting nucleus of normal rats and its up-regulation in neuropathic pain].

This study was aimed to observe the distribution of Mas-related G protein-coupled receptor A (MrgA) in cerebrospinal fluid (CSF)-contacting nucleus of normal rats and its expression in neuropathic pain, and to provide morphological evidence for CSF-contacting nucleus to participate in neuropathic pain. The model of neuropathic pain with chronic constriction injury (CCI) of the sciatic nerve was made in Sprague-Dawley rats. The thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured. The expressions of MrgA in the CSF-contacting nucleus were examined by double labeling with immunofluorescent staining. The results showed that on the 5th, 7th, 10th and 14th days, the values of MWT and TWL in CCI group were all lower than those in sham group (P < 0.05). MrgA was found to be distributed in CSF-contacting nucleus of normal rats; and the expression was markedly up-regulated in rats at the peak of neuropathic pain. Our data suggest that CSF-contacting nucleus may participate in neuropathic pain through the MrgA-mediated signaling pathway.

Contact fracture test of monolithic hybrid ceramics on different substrates for bruxism.

OBJECTIVES: To determine the minimum thickness required for a monolithic hybrid ceramic crown on different substrates (soft vs stiff) used in posterior dentition for bruxism. METHODS: 80 polymer-infiltrated ceramic networks Vita Enamic (PICN VE) disc specimens with four different occlusal thicknesses (0.8, 1.2, 1.6 and 2.0 mm), were produced using a computer-aided design/manufacturing system, and cemented on a stiff (zirconia) or soft (polyamide) substrate of 4-mm thickness. The ten specimens, in soft or stiff groups, were subjected to compressive loading by a MTS machine until fracture or maximum load (4500 N) was reached. The unbroken specimens were examined using optical coherence tomography. Eight axisymmetric finite element models and eight 3D models comprising the four different occlusal thicknesses and two substrates under different vertical loads and sliding movements were constructed. The maximum principal stress was selected to evaluate the stress distribution in this study. RESULTS: The fracture resistance of the specimens was significantly different between the two substrates (P < 0.001). Fracture resistance was positively associated with specimen thickness (r = 0.597 and 0.896 for the soft and stiff substrate respectively). Specimens on the soft substrate had lower fracture loads, whilst cone cracks were observed in unbroken samples on different soft/stiff substrate prior to final fracture. The finite element analysis confirmed that samples on the stiff substrate had lower maximum principal stress values than those on the soft substrate. For the maximum principal stress not to exceed the flexural strength of PICN VE, a stiff substrate and minimum thickness of 2.0 mm are required for the prostheses. SIGNIFICANCE: A minimum 2.0 mm thick, stiff substrate was needed for bruxism as shown by the effect of high/large chewing force on the posterior dentition of monolithic PICN VE crowns.

Antimicrobial limonoids from the seeds of Cipadessa cinerascensa.

Phytochemical investigation on the 90% EtOH extract of the seeds of Cipadessa cinerascensa led to the isolation of three new limonoids, cinerascenoids A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the limonoids were in vitro evaluated for their antimicrobial activities against six pathogenic microorganisms. Limonoids 1 and 2 exhibited some activities against three Gram negative bacteria with MIC values less than 60 µg/ml.

Exploring the Mystery of Osteoarthritis using Bioinformatics Analysis of Cartilage Tissue.

BACKGROUND: Osteoarthritis (OA) is a kind of chronic disease relating to joints, which seriously affectsthe daily life activities of the elderly and can also lead to disability. However, the pathogenesis of OA is still unclear, which leads to limited treatment and the therapeutic effect far from people's expectations. This study aims to filter out key genes in the pathogenesis of OA and explore their potential role in the occurrence and development of OA. METHODS: The dataset of GSE117999 was obtained and analyzed in order to identify the differentially expressed genes (DEGs), hub genes and key genes. We also identified potential miRNAs which may play a major role in the pathogenesis of OA, and verified their difference in OA by real-time quantitative PCR (RT-qPCR). DGldb was found to serve as an indicator to identify drugs with potential therapeutic effects on key genes and Receiver Operating Characteristic (ROC) analysis was used for identifying underlying biomarkers of OA. RESULTS: We identified ten key genes, including MDM2, RB1, EGFR, ESR1, UBE2E3, WWP1, BCL2, OAS2, TYMS and MSH2. Then, we identified hsa-mir-3613-3p, hsa-mir-548e-5p and hsamir- 5692a to be potentially related to key genes. In addition, RT-qPCR confirmed the differential expression of identified genes in mouse cartilage with or without OA. We then identified Etoposide and Everolimus, which were potentially specific to the most key genes. Finally, we speculated that ESR1 might be a potential biomarker of OA. CONCLUSION: In this study, potential key genes related to OA and their biological functions were identified, and their potential application value in the diagnosis and treatment of OA has been demonstrated, which will help us to improve the therapeutic effect of OA.

Colorectal cancer-associated fibroblasts promote metastasis by up-regulating LRG1 through stromal IL-6/STAT3 signaling.

Cancer-associated fibroblasts (CAFs) have been shown to play a strong role in colorectal cancer metastasis, yet the underlying mechanism remains to be fully elucidated. Using CRC clinical samples together with ex vivo CAFs-CRC co-culture models, we found that CAFs induce expression of Leucine Rich Alpha-2-Glycoprotein 1(LRG1) in CRC, where it shows markedly higher expression in metastatic CRC tissues compared to primary tumors. We further show that CAFs-induced LRG1 promotes CRC migration and invasion that is concomitant with EMT (epithelial-mesenchymal transition) induction. In addition, this signaling axis has also been confirmed in the liver metastatic mouse model which displayed CAFs-induced LRG1 substantially accelerates metastasis. Mechanistically, we demonstrate that CAFs-secreted IL-6 (interleukin-6) is responsible for LRG1 up-regulation in CRC, which occurs through a direct transactivation by STAT3 following JAK2 activation. In clinical CRC tumor samples, LRG1 expression was positively correlated with CAFs-specific marker, α-SMA, and a higher LRG1 expression predicted poor clinical outcomes especially distant metastasis free survival, supporting the role of LRG1 in CRC progression. Collectively, this study provided a novel insight into CAFs-mediated metastasis in CRC and indicated that therapeutic targeting of CAFs-mediated IL-6-STAT3-LRG1 axis might be a potential strategy to mitigate metastasis in CRC.

Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study.

BACKGROUND: Lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) exerted promising effects on unresectable hepatocellular carcinoma (uHCC). We assessed the safety and clinical efficacy of triple therapy [LEN+PD-1+transcatheter arterial chemoembolization (TACE)] in uHCC. METHODS: uHCC patients with an ECOG PS score of 0-1 and Child-Pugh class A who underwent triple therapy were included. The primary endpoint was objective response rate (ORR) based on mRECIST. Secondary endpoints were conversion rate to liver resection and treatment-related adverse events. RESULTS: Between November 2018 and December 2020, 62 uHCC patients who underwent triple therapy at four major cancer centers in China were analyzed, including 35 in BCLC-C, 21 in BCLC-B, and 6 in BCLC-A. With a median follow-up of 12.2 months (range, 7.6-33.3 months), the investigator and blinded independent central review-assessed ORR were 80.6% and 77.4%, respectively. A total of 33 patients (53.2%) reached the standard of conversion to resectable HCC and 29 patients underwent resection. The median interval between start of triple therapy and resection was 123 days (range, 55-372 days). Pathological complete response and major pathological response were observed in 16 and 24 patients, respectively. Median overall survival and progression-free survival were not reached. Treatment-related adverse events occurred in 74.2% of the patients (grade ≥3, 14.5%; grade ≥4, 4.8%). CONCLUSION: Combination of LEN, PD-1 and TACE showed a high rate of tumor response and convert resection in uHCC patients, with manageable toxicity.

Accurate Placement of Cannulated Screws in Femoral Neck Fractures: Screw and Guide Wire Combined Technique.

Cannulated screw fixation is widely used in the treatment of femoral neck fractures. During surgery, we often face the situation that a guide wire needs to be adjusted because of poor positioning in the femoral neck. It is difficult to adjust the direction of the guide wire in the neck of the femur due to its elasticity. This study developed a practical technique to adjust the guide wire to the correct position. When the direction of insertion of the guide wire has deviated, first, measure the length of the guide wire. Second, select the appropriate cannulated screw based on the measurement, and screw the cannulated screw in along the direction of the guide wire to Ward's triangle. Then return the guide wire to the front of the cannulated screw. At this time, the cannulated screw can be used as a built-in guide, and a screwdriver can be used to fine-tune the position of the screw to the optimal direction under the X-ray guidance. Finally, the cannulated screw is screwed in in this direction until it passes through the Ward triangle area, and the guide wire is inserted. This technique can help doctors insert a guide wire more quickly and accurately, reducing intraoperative injury and the operation time.