Aim To evaluate the efficacy of TFU as a precursor of 5-FU on the growth inhibition of human gastric carcinoma cell lines SGC-7901 and MKN-45.Methods In vitro experiments,cell growth inhibition was measured by MTT assay.The rates were compared in the presence and Absence of liver microsomal enzymes.The morphology of apoptotic cells was detected by observation with a fluorescence microscope after staining by using adridine orange/ethidium bromide solution.DNA fragmentation was analyzed by agarose gel electrophoresis and flow cytometry respectively.Western blot was employed to analyze the expression of Bcl-2 and Bax.The in vivo efficacy of TFU was assessed in nude mice bearing tumours.The specimens were re-moved and the in situ cell apoptosis detection kit was employed for TUNEL staining.Results Growth of SGC-7901 and MKN-45 cells was remarkably suppressed by treatment with TFU in the presence of liver microsomal enzymes in vitro,suggesting that TFU might be converted to 5-FU by the enzymes.Similar treatment of TFU induced apoptosis of the cells,which was deduced from typical apoptotic features such as morphology,the formation of characteristic ladder pattern of DNA migration and the accumulation of sub-G1 phase.Furthermore,a significant inhibition of Bcl-2 expression and the up-regulation of Bax were observed after treatment with TFU in the presence of liver microsomal enzymes.Growth of human gastric carcinoma cells was significantly delayed by oral administration of TFU with low side effects.Apoptosis in xenografts was also observed by means of TUNEL staining method.Conclusion Treatment of TFU in the presence of liver microsomal enzymes could promote the inhibition of gastric carcinoma cell proliferation.TFU might sustain release of 5-FU mediated by liver microsomal enzymes.Low dose of 5-FU might trigger the carcinoma cells apoptosis via regulation of Bax and Bcl-2.

This paper describes the inhibitory effects of antineoplaston A10 with using different dosages against the mouse S180, rats W256 and Bca - P6 and MGC cell (human) in nude mouse. When the administered dosage of oral formulation antineoplaston A10 was 4000mg ? kg-1 ? 24h-1 against the S180 for 10d . inhibitory rate was 32. 5%( P

Objective To investigate the abnormalities of brain gray matter volume in patients with clinically-confirmed essential tremor (ET)of the hands only.Methods We analyzed brain gray matter voxel of 1 7 patients (younger than 55 years)with ET of the hands only and 1 7 healthy controls matched in age,gender and education by optimized voxel-based morphometry (VBM).Results VBM showed marked expansion of the bilateral cerebella, occipital fusiform cortices,and precentral lobes (P uncorrected < 0.005 )in ET patients compared with the controls. Atrophy was only detected in left parietal lobe.We also found volume enlargement in the thalamus,midbrain,and melluda of the left side by region of interest (ROI )analysis (P uncorrected <0.005).Conclusion Patients with arm tremor show expansion of gray matter,which might represent the adaptive reorganizational compensation through the increased demand on the visuospatial control of skilled movements in ET patients with early-stage arm tremor. These morphological changes may help to assess early stage and distinguish subtype of ET.

Objective: To evaluate the short-term efficacy of Broström-Gould repair combined with Internal Brace artifi-cial ligament reinforcement under arthroscopy for anterior talofibular ligament injury in overweight and poor ligament quality popu-lation. Methods: A total of 12 patients with anterior talofibular ligament injury treated by arthroscopy were enrolled from October 2017 to May 2018, involving 7 males and 5 females aged from 16 to 57 years old (mean 32.4 years). Patients were with ankle insta-bility, and their BMI was 28.0-30.7 kg/m² (average, 28.8±0.91 kg/m²), among which there were 2 cases of poor ligament quality (Beighton score ≥4). The anterior tibiofibular ligament injury and the quality of the ligament stump were intraoperatively evaluated under arthroscopy. A 4.75 mm diameter anchor with Internal Brace artificial ligament was inserted into the fibula insertion site, and non-absorbable suture was placed at the talus under total arthroscopy. Firstly, the non-absorbable line on the anchor was per-formed under the standard Broström-Gould procedure to repair the anterior talofibular ligament, and the other end of the ligament was fixed near the distal end of the talus. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and foot and ankle ability measure (FAAM) was compared before and after surgery. Results: All the incisions were healed in the first stage after operation, and no operative complications such as infection occurred. All the 12 patients were followed up for 7 to 12 months (average 9.1 months). After 2 weeks, the patient began functional exercise and could walk with ankle braces. At the latest follow-up, the anterior drawer test was negative. The ankle-posterior foot score of AOFAS was increased from 61.3±7.9 (preopera-tive) to 85.0±6.0 (latest follow-up) (t=21.422, P< 0.01), and the FAAM score was increased from 57.5±10.1 (preoperative) to 86.3±4.8 (latest follow-up) (t=15.032, P< 0.01). AOFAS score was excellent in 1 case and good in 11 cases. The excellent and good rate was 100% (12/12). No complications such as infection and re-rupture occurred after operation. Conclusion For anterior talofibu-lar ligament injury patients with overweight or poor quality of ligament, the Broström-Gould procedure can be applied to strengthen under arthroscopic Internal Brace ligament without additional tendon reconstruction, which can also obtain good results.

OBJECTIVE: To investigate the available operation method of special type tracheobronchial foreign bodies removal. METHOD: Sixty one patients of special type tracheobronchial foreign bodies were extracted with some special instruments and methods depend on foreign body types. The features of operation on different kinds of foreign bodies were analyzed. RESULT: All patients were operated successfully by using foreign body hook (31 cases), pencil or writing screw brush extracted (11 cases), foreign body cage (13 cases), slender inverse claw esophagus foreign body clamp (3 cases) and so on. No complications and died cases were found. Only 5 patients were undertaken trachea incision before operation. CONCLUSION Suitable instruments and technique chose for every individual cases is the key to successful operation.
Adolescent ; Adult ; Aged ; Bronchi ; Bronchoscopy ; methods ; Child ; Child, Preschool ; Female ; Foreign Bodies ; surgery ; Humans ; Male ; Middle Aged ; Trachea ; Treatment Outcome ; Young Adult

Objective:To compare the efficacies of arthroscopic modified Brostr?m procedure combined with or without peroneal tendon debridement in the treatment of chronic lateral ankle instability (CLAI) concomitant with fibular tendinitis.Methods:A retrospective cohort analysis was conducted on the clinical data of 31 patients with CLAI concomitant with fibular tendinitis, who were treated in Beijing Tongren Hospital, Capital Medical University between March 2019 and December 2021. The patients included 17 males and 14 females, aged 16-57 years [(32.8±9.6)years]. The anterior drawer test and talar tilt test were positive in all patients preoperatively. Diagnosis was confirmed by physical examination and MRI, and calcaneofibular ligament rupture was excluded. Eleven patients received arthroscopic modified Brostr?m procedure combined with peroneal tendon debridement (modified Brostr?m procedure+tendon debridement group), and 20 underwent pure arthroscopic modified Brostr?m procedure (modified Brostr?m procedure group). The operation time, intraoperative blood loss and length of hospital stay were documented. The visual analogue score (VAS) in peroneal tendon area was assessed before operation and at postoperative 2, 6 and 12 weeks. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and foot and ankle outcome score (FAOS) were assessed before operation and at postoperative 6 and 12 weeks. The anterior drawer test was performed at the last follow-up. The foot and ankle ability measure (FAAM) score was assessed before operation and at the last follow-up. Postoperative wound healing and complications were also observed.Results:All the patients were followed up for 4-19 months [(11.3±3.5)months]. The operation time was (66.0±4.2)minutes in the modified Brostr?m procedure+tendon debridement group, which was significantly longer than (61.5±3.4)minutes in the modified Brostr?m procedure group ( P<0.05). There was no significant difference in intraoperative blood loss or length of hospital stay between the two groups (all P>0.05). Compared with the preoperation, the value of VAS was significantly lowered, and the values of AOFAS ankle-hindfoot score, FAOS and FAAM score were significantly increased at different postoperative timepoints (all P<0.01). No significant differences in the values of VAS, AOFAS ankle-hindfoot score, FAOS or FAAM score were seen between the two groups before operation (all P>0.05). The value of VAS was 3.0(3.0, 4.0) points in the modified Brostr?m procedure+tendon debridement group, being markedly different from 4.0(4.0, 4.0)points in the modified Brostr?m procedure group at 2 weeks postoperatively ( P<0.05). The value of VAS was 2.0(1.0, 3.0)points in the modified Brostr?m procedure+tendon debridement group, being markedly different from 3.0(2.3, 3.0)points in the modified Brostr?m procedure group at 6 weeks postoperatively ( P<0.05). At 12 weeks postoperatively, there was no significant difference in the value of VAS between the two groups ( P>0.05). There were no significant differences in the values of AOFAS ankle-hindfoot score and FAOS between the two groups at 6 or 12 weeks postoperatively (all P>0.05). The anterior drawer test was negative in all patients at the last follow-up. No significant difference was seen in the value of FAAM score between the two groups at the last follow-up ( P>0.05). All incisions were healed well in the first stage after operation, without the occurrence of joint infection, impaired joint motion, nerve injury or deep vein thrombosis. Conclusions:Arthroscopic modified Brostr?m procedure combined with or without peroneal tendon debridement can both improve the foot function in CLAI patients concomitant with fibular tendinitis. However, the combined treatment allows for early pain relief, without increasing the risk of complications, and can therefore contribute to a faster postoperative recovery.

OBJECTIVE: This paper used plantar pressure analysis equipment to discuss the plantar pressure distribution pattern and balance ability of patients with the knee joint injury under static standing. METHODS: Zebris FDM-S plantar pressure analysis equipment was used to collect plantar pressure data from subjects with the knee joint injury and healthy control subjects. We compared the pressure values in each region of pelma, and then assessing the balance ability of the subjects based on the trajectory of the overall pressure center movement. RESULTS: Compared with the healthy control group, patients with knee joint injury have a significantly lower pressure in the heel areas and a significantly higher pressure in the middle foot area. And the total pressure of the injured limb foot in the patient group is lower than that in the contralateral foot. In addition, there is a significant increase in the parameters of the balance ability index in the patient group. CONCLUSIONS The plantar pressure distribution pattern of patients with knee joint injury is different from that of normal people in static standing, and the balance ability is poor. Therefore, this method has a positive guiding significance in the evaluation and application of knee joint injury.
Biomechanical Phenomena ; Equipment Design ; Foot ; Gait ; Humans ; Knee Joint ; Pressure

Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130‒Cys141) to the RING domain of MEX3A through the conformational changes of βarr2. The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants βarr2^Y64A and βarr2^Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A. The truncated-βarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.