Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

OBJECTIVE： To investigate the relationship between ATP-binding cassette subfamily B member 1 （ABCB1） polymorphism and tacrolimus-related adverse drug reactions in renal transplant patients during perioperative period. METHODS： Totally 170 patients who underwent renal transplantation from Nov. 2014 to Mar. 2018 in our hospital as well as were tested for their ABCB1 C1236T （rs1128503）， ABCB1 G2677T/A （rs2032582） and ABCB1 C3435T （rs1045642） genotype were selected in this study. χ2 test was used to compare the incidence of tacrolimus-related ADR among patients with different genotypes. The related adverse reactions included digestive tract reaction， pulmonary infection， renal dysfunction， abnormal liver function， elevated blood sugar， elevated blood lipid and decreased white blood cells. Logistic regression model was used to analyze the unit point risk. The main haplotypes of the above genes were analyzed by PHASE software， and their correlation with tacrolimus-induced ADR was analyzed. RESULTS： Among 170 patients， 21 cases （12.3％） of CC type， 78 cases （45.9％） of CT type and 71 cases （41.8％） of TT type were detected by ABCB1 C1236T （rs1128503）. ABCB1 G2677T/A （rs2032582） test showed that 25 cases （14.7％） were GG type， 95 cases （55.9％） were GA+GT type and 50 cases （29.4％） were AA+AT+TT type. ABCB1 C3435T （rs1045642） test showed that 57 cases （33.5％） were CC type， 82 cases （48.2％） were CT type and 31 cases （18.3％） were TT type. There was no significant difference in the incidence of digestive tract reaction， pulmonary infection， renal dysfunction， elevated blood sugar， elevated blood lipid and decreased white blood cells among patients with different ABCB1 genotypes （P＞0.05）. However， there was significant difference in the incidence of abnormal liver function between ABCB1 C1236T （rs1128503） and ABCB1 C3435T （rs1045642） genotypes （P＜0.05）. There was no significant difference in the incidence of abnormal liver function among ABCB1 G2677T/A （rs2032582） genotypes （P＝0.069）， but P was lower than 0.1. Logistic regression analysis showed that ABCB1 C1236T （rs1128503） CC genotype [OR＝4.959， 95％CI （1.700， 14.468）， P＝0.003]， ABCB1 G2677T/A （rs2032582） GG genotype [OR＝3.500， 95％CI （1.164， 10.524）， P＝0.026] and ABCB1 C3435T （rs1045642） CC genotype [OR＝3.033， 95％CI （1.012， 9.095）， P＝0.048] were risk factors for tacrolimus-related abnormal liver function. ABCB1 CGC haplotype was the main haplotype. There was significant difference in the incidence of abnormal liver function caused by tacrolimus between ABCB1 CGC haplotype and non-ABCB1 CGC haplotype （P＝0.002）， and it was also a risk factor for tacrolimus-related liver dysfunction [OR＝3.173， 95％CI（1.512， 6.656）， P＝0.002]. CONCLUSIONS： The abnormal liver function of ABCB1 CGC haplotype kidney transplantation patients is more likely to occur when tacrolimus is administered during the perioperative period.

Objective To explore the effect of preoperative simulation training on surgical indicators and postoperative infection in patients with intestinal obstruction. Methods From November 2015 to November 2016, 66 patients with intestinal obstruction who received routine nursing in the Second People's Hospital of Wuxi were selected as control group. From December 2016 to December 2017,66 patients with intestinal obstruction surgery who received preoperative simulation training in our hospital were selected. as observation group. The surgical indicators and postoperative infections were compared between the two groups. Results The incision pain time,first exhaust time,land time and the hospitalization time in the observation group were (2. 19 ± 1. 08) d,(1. 53 ± 0. 72) d, (5. 21 ± 0. 98)d,(9. 75 ± 1. 49)d,respectively,which were shorter than those in the control group (all P < 0. 05). The CRP levels at postoperative 1 d,3 d and 6 d in the observation group were (6. 36 ± 1. 57) mg/ L,(7. 36 ± 1. 21)mg/ L,(6. 38 ± 1. 19)mg/ L,respectively,the PCT levels were (0. 46 ± 0. 14)ng/ mL,(0. 60 ± 0. 11)ng/ mL, (0. 38 ± 0. 06) ng/ mL, respectively, which were all lower than those in the control group, the differences were statistically significant ( all P < 0. 05). Conclusion Preoperative simulation training for patients with intestinal obstruction surgery can effectively optimize the surgical indicators and improve postoperative infection,and it is worthy of popularizing and applying.

Objective To observe the anatomy of the radial proper digital arteries and their dorsal vessels of index fingers, and the relative position and orientation of them were summarized. To explore the surgical method and clinical appilication of the stepladder advancement flap pedicled with the radial proper digital artery of index finger in the finger tip defects. Methods From June, 2013 to June, 2016, 6 hand specimens were injected into the brachial artery with red latex to carry out the microanatomy of the index finger’s radial proper digital arteries and their dorsal vessels. And 1 vascular cast of hand specimen were observed the origin, number and oriention of the artery and its dorsal vessel. Ten cases with soft tissue defects of index finger in finger tip, were repaired with stepladder advance-ment flap pedicled with the radial proper digital artery. The evaluations and analysis were made in survival rate and finger's function by the postoperative regular consultations. Results There were 2 (4 hands) or 3 (2 hands) dorsal vessels in the proximal, and 2(6 hands) in middle segments of the radial proper digital arteries of index fingers in 6 hand specimens respectively. While the vascular cast of hand specimen showed that 3 dorsal vessels in the proximal, and 2 in the middle segments of the radial proper digital artery. Ten patients were performed the operation. The blood flow after the surgery were good and all flaps survived well. Followed-up time was 10-14 months. The color, feeling, contour and texture of flaps was good. The function of flexion and extension of the finger was good too, and no defor-mity of the purlicue. The resolution of static two points was 5.5-9.0 mm, averaged of 7.2 mm. Conclusion The stepladder advancement flap pedicled with the radial proper digital artery of index finger can extend the donor site. It is safe, reliable and effective, providing a alternation for the repair of the soft tissue defects of the index finger tip.

Objective To determine the outcome of the combined use of flaps transfer and ilizarov technique reconstruct the large soft tissue defects and bone lose in the lower leg.Methods Sixteen patients were identified from a retrospective review from July,2008 to July,2013,who suffered the large soft tissue defects and bone lose in the lower leg and underwent single-stage soft tissue and osseous reconstruction using the flap technique and Ilizarov method.There were 12 males and 4 females aged from 22 to 62 years old (average 42.6 years old).The size of soft tissue defect ranged from 8 cm×9 cm to 30 cm×20 cm.The length of the bone discrepancy ranged from 2 to 14 cm.According to the local condition of the lower leg and the size of the composite tissue defects,10 patients received the free flap covering,6 patients repaired by the saphenous neurocutaneous perforator flap (3 cases) and sural nerve neurocutaneous flap (3 cases).Daily monitoring the skin temperature postoperative.Distraction was commenced on postoperative day 10 to 14 at the rate of 1 mm/day and continued in 4 equal increments.Results The follow-up time ranged from 18 to 36 months.Sixteen flaps survived completed,only 1 flap was observed the venous congestion in postoperative day 2.The duration of ilizarov application ranged from 3.5 to 18.0 months.All patients achieved final union.All patients were satisfied with the outcome of the surgery.Conclusion The combined use of neurocutaneous flap and Ilizarov technique for reconstruction of large composite soft tissue defect in the lower leg.Significantly reduce patient treatment time,improving traction osteogenesis of long bones and the ability of resistance to infection.

Objective To explore the multi-modal MRI characteristics of breast cancers in dense breasts.Methods 120 patients with breast cancer shown on mammography underwent breast MRI,which were solitary and confirmed by pathological examination. According to the BI-RADS classification of breast,the 120 cases were divided into two groups including dense type breast and non-dense type one.The differences in morphological features,ADC values (b=1 000 s/mm2 )and time-signal intensity curve (TIC)of the lesions between two groups were analyzed and compared.Statistical analysis was performed using SPSS1 6.0.Results The breast cancers in dense breast were vulnerable to have a spiculated margin (44/68 in the dense breast group vs.1 6/52 in the non-dense breast group,P =0.000).The size of the lesion in dense breast (1.83 ±0.98)cm was bigger than that in non-dense breast (1.40±0.46)cm (P =0.005).The non-mass-like enhancement of the lesion in dense breast was much more than that in non-dense breast (P =0.000).In addition,the average ADC values of the lesion in dense breast (0.89±0.12)×10 -3 mm2/s were lower than in non-dense breast (0.95±0.10)×10 -3 mm2/s(P =0.01 6).Conclusion The breast cancer in the dense breast has different MRI findings in comparison with non-dense breast.

BACKGROUND:Dorsal digital block refers to the commonly used anesthesia for adults in smal or moderate hand injury surgeries, but in recent years, modified transthecal digital block technique is gradualy respected, which is favored with a rapid and good effect and fewer complications.
OBJECTIVE:To evaluate the clinical anesthetic outcomes of modified transthecal digital block and traditional dorsal digital block technique for the treatment of hand injury of adults in emergency by a prospective randomized controled study.
METHODS:Totaly 60 adult patients with hand injury were enroled and divided into two groups of modified transthecal digital block and traditional dorsal digital block randomly. Blocks were performed by one single surgeon. The operation time, local anesthetic dose, onset time of anesthesia, duration of anesthesia, success rate of anesthesia, visual analogue scale scores and complications were recorded.
RESULTS AND CONCLUSION:The anesthesia effects in the two groups were acceptable. There was no significant difference in the onset time of anesthesia, duration of anesthesia, success rate of anesthesia and complications between the two groups (P > 0.05). The operation time of anesthesia, local anesthetic dose, and visual analogue scale scores were significantly different between the two groups (P< 0.05). Modified transthecal digital block is more convenient and has less pain than the traditional root digital block, which is a safe and reliable anesthetic technique.

Objective To investigate the diagnosis and treatment of splenic space occupying lesions associated with comorbidity.Methods The clinical data of 5 patients from Jiangyin People' s Hospital and 9 patients from Wuxi People's Hospital from January 2002 to June 2012 were retrospectively analyzed.All the patients suffered from splenic space occupying lesions associated with comorbidity.Splenectomy or multi-visceral resection were selected according to the results of preoperative B sonography and computed tomography examination.Chemotherapy regimes were selected based on postoperative pathological examination.All the patients were followed up till June 2013.Results The symptoms of patients with splenic space occupying lesions were non-specific.The first symptoms of 4 patients were discomfort or distending pain of left upper abdomen,and the other 10patients had no symptoms.The coincidence rate of preoperative diagnosis was 10/14,and the coincidence rate of preoperative diagnosis for patients with malignant tumors was 2/5.Fourteen patients received preoperative B ultra-sonography,and 9 were definitively diagnosed.Nine patients received computed tomography,and 7 were definitively diagnosed.Of the 14 patients,right ovarian cancer,bilateral ovarian cancer and sigmoid colon cancer were correlated with solitary splenic metastasis,and the main lesions of the other 11 patients were not correlated with splenic space occupying lesions.The main lesions of patients with left colon carcinoma,type 2 diabetes and vascular tumor of the spleen,patients with renal carcinoma and splenic sclerosing hemangioma,and patients with hypertension,cholecystolithiasis and splenic lymphangioma were diagnosed simultaneously with the splenic space occupying lesions,and the main lesions of theother 11 patients were diagnosed separately with the splenic space occupying lesions.Ten patients underwent simple splenectomy and 4 patients received multi-visceral resection.Chemotherapy regimens were selected according to the type of main lesions for 5 patients who were diagnosed by pathological examinations.All the patients were recovered smoothly with no occurrence of severe infections.Two patients with splenic sarcoma had tumor metastasis at postoperative 6 months and 1 year,respectively.One patient with right ovarian cancer and solitary splenic metastasis had transverse colonic metastasis at postoperative 3 years.One patient with bilateral ovarian cancer and solitary splenic metastasis had peritoneal metastasis at postoperative 2 years.One patient with sigmoid colon cancer and solitary splenic metastasis died of peritoneal tumor recurrence at postoperative 4 years.One patient with left colon carcinoma,type 2diabetes and vascular tumor of the spleen survived for 6 years and was still sound and well.The other 9 patients with benign disease survived within the period of follow-up.Conclusions The definitive diagnosis for patients with splenic space occupying disease associated with comorbidity depends on the preoperative imaging examination and postoperative pathological examination.Surgical treatment is safe when operative contraindications are excluded.The prognosis of patients is determined by the progress of main lesions and the character of splenic space occupying lesions.

OBJECTIVE: To investigate the relationship between the promoter polymorphism of IL6 (-174G > C, -572G > C and -597G > A) and chronic rhinosinusitis (CRS). METHOD: The case-control study consisted of 123 patients with CRS and 239 controls from a Chinese Han population from Shanghai. The genotypes of the subjects were determined by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. Besides, the concentrations of the totle immunoglobulin E (TIgE) and eosinophilic cationic protein (ECP) in the blood were also determined. RESULT: The -174G > C and -597G > A polymorphisms were not detected in this study population. Significant differences in genotype and allele frequencies of -572C/G were observed between CRS patients and control groups. In CRS patients, the CC, CG, GG genotype frequencies were 69.1%, 29.3%, 1.6%, C, G allele frequencies were 83.7%, 16.3%. In control group, the genotype frequencies were 55.2%, 42.3%, 2.5%, the allele frequencies were 76.4%, 23.6%, respectively. The -572CC genotype was associated with an increased risk of developing CRS (P < 0.05, OR = 1.932, 95% CI, 1.205-3.097). There was no significant differences in the concentrations of the TIgE and ECP among each genotype. CONCLUSION IL-6 gene -572G > C polymorphism is associated with the susceptibility to CRS. CC genotype could be an independent risk factor.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; China ; Chronic Disease ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-6 ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors ; Sinusitis ; genetics ; Young Adult