Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; HSP70 Heat-Shock Proteins ; blood ; Humans ; Lead ; toxicity ; Male ; Occupational Exposure

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

OBJECTIVETo analyze the Millard II technique for correcting secondary deformities of unilateral cleft lip.

METHODSThe Millard II technique was used to correct secondary deformities of unilateral cleft lip in 42 patients from March of 2003 to September of 2004. Dissection was made between the alar cartilage and skin, and the alar cartilage was suspended.

RESULTSThe postoperative follow-ups with 3 approximately 6 months revealed good results of the symmetrical nostrils and philtrums, prolonged columella nasi, good-shaped cupid's bow, and invisible scar.

CONCLUSIONSThe Millard II technique could be an ideal method to correct secondary deformities of unilateral cleft lip. Releasing and suspending alar cartilage spontaneously at the same time can correct nasal deformity adequately.

Adolescent ; Adult ; Child ; Child, Preschool ; Cleft Lip ; etiology ; surgery ; Female ; Humans ; Male ; Nose ; abnormalities ; Nose Deformities, Acquired ; surgery ; Postoperative Complications ; surgery ; Reconstructive Surgical Procedures ; methods ; Young Adult

OBJECTIVETo explore the method of constructing tissue-engineered skin using melanocytes and bone marrow mesenchymal stem cells (BMSCs) in vivo.

METHODSMelanocytes were isolated from human foreskin. BMSCs were isolated from human bone marrow. Both of them were co-cultured at a ratio of 1:10, and then were implanted into the collagen membrane to construct the tissue-engineered skin, which was applied for wound repair in nude mice. The effectiveness of wound repair and the distribution of melanocytes were evaluated by morphological observation, in vivo 4,6-diamidino-2-phenylindole, dihydrochloride (DAPI) fluorescent staining tracing, HE staining, S-100 immunohistochemistry, and transmission electron microscopy.

RESULTSThe wounds were satisfactorily repaired among the nude mice. The melanocytes were distributed in the skin with normal structure, as confirmed by DAPI fluorescent staining tracing, HE staining, S-100 immunohistochemistry, and transmission electron microscopy.

CONCLUSIONMelanocytes and BMSCs, after proper in vitro culture at an appropriate ratio, can construct the tissue-engineered skin with I type collagen membrane.

Animals ; Bone Marrow Cells ; cytology ; Cells, Cultured ; Coculture Techniques ; Collagen Type I ; Humans ; Melanocytes ; cytology ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Nude ; Skin ; injuries ; Skin, Artificial ; Tissue Engineering

OBJECTIVETo explore the plastic surgical repairment of the large wound of endometriosis in the abdominal wall.

METHODSince March 2003 to December 2004, 6 patients were treated with abdominoplasty and V-Y plasty for the wounds of the endometriosis in the abdominal wall.

RESULTSThe endometriotic foci were removed thoroughly with pretty abdominal contour. No complications were observed.

CONCLUSIONAbdominoplasty and V-Y plasty are good methods to repair the wounds of the endometriosis in the abdominal wall.

Abdominal Wall ; surgery ; Adult ; Cesarean Section ; adverse effects ; Endometriosis ; etiology ; surgery ; Female ; Follow-Up Studies ; Humans ; Pregnancy ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps

OBJECTIVETo compare the efficacy difference in the treatment of supraspinous ligament injury between floating acupuncture at Tianying point and the conventional warm needling therapy.

METHODSNinety patients were randomized into a floating acupuncture group and a warm needling group, 45 cases in each one. In the floating acupuncture group, the floating needling technique was adopted at Tianying point. In the warm needling group, the conventional warm needling therapy was applied at Tianying point as the chief point in the prescription. The treatment was given 3 times a week and 6 treatments made one session. The visual analogue scale (VAS) was adopted for pain comparison before and after treatment of the patients in two groups and the efficacy in two groups were assessed.

RESULTSThe curative and remarkably effective rate was 81.8% (36/44) in the floating acupuncture group and the total effective rate was 95.5% (42/44), which were superior to 44.2% (19/43) and 79.1% (34/43) in the warm needling group separately (P < 0.01, P < 0.05). VAS score was lower as compared with that before treatment of the patients in two groups (both P < 0.01) and the score in the floating acupuncture group was lower than that in the warm needling group after treatment (P < 0.01). Thirty-six cases were cured and remarkably effective in the floating acupuncture group after treatment, in which 28 cases were cured and remarkably effective in 3 treatments, accounting for 77.8 (28/36), which was apparently higher than 26.3 (5/19) in the warm-needling group (P < 0.01).

CONCLUSIONThe floating acupuncture at Tianying point achieves the quick and definite efficacy on supraspinous ligament injury and presents the apparent analgesic effect. The efficacy is superior to the conventional warm-needling therapy.

Acupuncture Points ; Acupuncture Therapy ; methods ; Adolescent ; Adult ; Aged ; Female ; Humans ; Longitudinal Ligaments ; injuries ; Male ; Middle Aged ; Pain Management ; Treatment Outcome ; Young Adult

Objective To analyze the current status of physical activities for children with intellectual disabilities based on ICF, to discuss the effects of physical activities on the health, and the approaches and its precautions.Methods The theory and method of ICF had been adopted. Literature review and theoretical research methods were implemented.Results In the way of participating physical activity, children with intellectual disabilities would improve not only their physical fitness, but also their mood and quality of life, and reduce their health risks.Conclusion Children with intellectual disabilities faced barriers in physical activities. It recommended to develop policies and provide support and guidance services to promote their participation of physical activities. It is necessary to develop policies to encourage children with intellectual disabilities to participate in community-based physical activities and provide adaptive facility and equipment, guidance and supportive services.

Objective To estimate the diagnostic value of cytology, DNA-ICM(DNA-image cytometry),cytology combined with DNA-ICM for pancreatic malignancy,and to explore the cut-off value for DNA-ICM. Methods Patients with suspicious pancreatic malignancy were retrospectively identified. In total,145 EUS-FNA specimens acquired from 140 separate patients were examined by cytology and DNA-ICM. Diagnostic values among cytology, DNA-ICM and the combination of the techniques in detecting pancreatic malignancy were compared. Results Compared with cytology, DNA-ICM had a lower sensitivity (63.0% VS 82.4%)and accuracy(69.7% VS 85.5%). After combining the techniques, the diagnostic value for pancreatic malignancy significantly improved compared with that by cytology(0.941 VS 0.912, P=0.007 0)or DNA-ICM only(0.941 VS 0.815, P<0.000 1). By using the Youden index, the cut-off value for DNA-ICM to detect pancreatic malignancy was one cell with DI(DNA index)≥2.5. Notably,with this standard, the sensitivity and accuracy of DNA-ICM significantly increased to 72.3% and 77.2%, and those of the combined techniques increased to 91.6% and 93.1%, respectively. Conclusion Automated DNA-ICM is an objective and effective method for pancreatic malignancy. Although DNA-ICM has a lower diagnostic value than that of conventional cytology, an improved value was obtained after combining the techniques.

In order to investigate the effects of different terms of inhaled nitric oxide (NO) preconditioning with low concentration on the activations of Toll-like receptor 2 and 4 (TLR2/4) in the lung ischemia-reperfusion (IR) injury in mice, we divided the male C57BL mice into five groups: sham (S) group, IR group, NO 1-min preconditioning group (15 ppm NO inhalation for 1 min before ischemia, NO 1-min), NO 10-min preconditioning group (15 ppm NO inhalation for 10 min before ischemia, NO 10-min), NO 60-min preconditioning group (15 ppm NO inhalation for 60 min before ischemia, NO 60-min). The changes of partial pressure of oxygen in artery (PaO2), left lung wet-to-dry weight ratio (W/D), and myeloperoxidase (MPO) in the injured lung were measured in every group at 6th h of reperfusion after 60 min of left lung ischemia. The changes of TLR2/4 activations and plasma TNF-α were measured in this procedure in additional mice. As compared with IR group, PaO2 increased, MPO and W/D decreased evidently after reperfusion in NO 10-min group. The changes in NO 60-min group were similar to those in NO 10-min group. There was no difference between NO 1-min and IR group. In NO inhalation group, the expressions levels of TLR2/4 mRNA and proteins were diminished, TNF-α concentrations were decreased, and the lung injuries were ameliorated effectively. We concluded that short term inhalation of NO protected lung IR injury. But the protective effect of NO was not increased with extension of inhaled NO. Inhaled NO could inhibit the activations of TLR2/4 in the lung after IR injury. TLR signal pathway might contribute to the effect of protection with NO in this model.
Administration, Inhalation ; Animals ; Dose-Response Relationship, Drug ; Lung ; drug effects ; metabolism ; Lung Injury ; metabolism ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide ; administration & dosage ; Reperfusion Injury ; metabolism ; prevention & control ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 4 ; metabolism ; Treatment Outcome

OBJECTIVETo establish HPLC fingerprints of Liuwei Dihuang condensed pills.

METHODDikma Diamonsil C18 column (4.6 mm x 250 mm, 5 microm) was adopted, with acetonitrile (containing 0.05% phosphoric) -water (containing 0.05% phosphoric) as the mobile phase. The column temperature was set at 40 degrees C, and the flow rate was 1.0 mL x min(-1). The detection wavelength was 276 nm (0-10 min), 236 nm (10-40 min) and 276 nm (40-60 min). The sample size was 20 microL. Chromatographic peaks were identified by Q-TOF-MS-IDA-MS/MS method.

RESULTGood precision, stability and repeatability were proved. Q-TOF-MS-IDA-MS/ MS method was adopted for qualitative determination of eighteen chromatographic peaks. Ten batches of Liuwei Dihuang condensed pills were determined with the method, and their similarities were above 0. 96.

CONCLUSIONThe study lays a foundation for the overall quality evaluation of Liuwei Dihuang condensed pills.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; standards ; Quality Control ; Tablets ; analysis