A middle-aged female with abnormal liver function indicators was admitted to hospital with obstructive jaundice. Urine protein of the patient was positive, and the color turned green during the retest with sulfosalicylic acid, which was relatively rare. According to the laboratory examination and other auxiliary diagnosis of the patient, the cause of the discoloration was found to be obstructive jaundice induced by choledochal adenocarcinoma, which impeded the excretion of copper ions through the bile of the patient. Copper enters the urine through the circulation of the bile, causing an increase in urinary copper. This provides a theoretical basis for the discovery of this phenomenon in clinical tests.

BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance

Objective:To investigate the safety and effectiveness of cytoreductive nephrectomy and tumor thrombectomy in patients with metastatic renal cancer with renal vein or inferior vena cava tumor thrombus.Methods:From February 2015 to May 2019, 56 cases of metastatic renal cell carcinoma with venous tumor thrombus were analyzed retrospectively, including 44 male (78.6%) and 12 female (21.4%)cases, and the average age was (59.2±10.7)(22-82). The clinical presentations covered local symptoms in 26 cases (46.4%), systemic symptoms in 8 cases (14.3%), both local symptoms and systemic symptoms in 12 cases (21.4%), and asymptomatic in 10 cases (17.9%). Among them, renal tumors were located in 35 cases (62.5%) on the right and 21 cases (37.5%) on the left. The average tumor diameter was (10.1±3.8)(1.5-21.1) cm. Forty-five cases (80.4%) scored 2 points and 11 cases (19.6%) scored 3 points by the American Society of anesthesiologists(ASA). Preoperative hemoglobin was (118.2±23.1)(72-178) g/L, and albumin was (37.9±5.6)(23-50) g/L, total protein was (67.7±6.7)(43-81) g/L, serum creatinine was (111.3±119.6)(32-958) μmol/L. There were 16 cases of Mayo 0 (28.6%), 14 cases of Mayo Ⅰ(25.0%), 17 cases of Mayo Ⅱ(30.4%), 4 cases of Mayo Ⅲ(7.1%), and 5 cases of Mayo Ⅳ(8.9%). Fourteen cases (25.0%) were in the stage of cN 0 and 42 cases (75.0%) in the stage of cN 1. Five cases (8.9%) had simple bone metastasis, 16 cases (28.6%) had simple lung metastasis, 2 cases (3.6%) had simple adrenal metastasis, 6 cases (10.7%) had simple liver metastasis, and 27 cases (48.2%) had 2 or more multiple system metastasis. According to the location of the organ system, 91 metastatic lesions were found in 56 patients. Among them, 37 cases (40.7%) had lung metastasis, 18 cases (19.8%) had liver metastasis, 21 cases (23.1%) had bone metastasis and 15 cases (16.5%) had adrenal metastasis. All 56 patients belonged to IMDC prognosis score model medium risk group. The surgical treatment of Mayo grade 0 tumor thrombus was the same as that of routine radical nephrectomy. The tumor thrombus of Mayo grade Ⅰ was removed after IVC was partially blocked by Satinsky′s forceps. The Mayo Ⅱ tumor thrombus was removed, after blocking the distal vena cava, the contralateral renal vein and the proximal vena cava. Mayo grade Ⅲ tumor thrombus needed pringer's method to block the first porta hepatis. For grade Ⅳ tumor thrombus the diaphragm could be cut directly, or the thrombus could be removed by cardiopulmonary bypass. Laparoscopic surgery was performed in 22 cases (39.3%) and open surgery in 30 cases (53.6%). Six cases (10.7%) underwent IVC wall resection because of tumor invasion. 32 cases (57.1%) underwent ipsilateral adrenalectomy because of tumor invasion or adrenal metastasis, and 23 cases (41.1%) underwent ipsilateral lymphadenectomy. In this study, there were 11 cases of solitary metastasis, 8 cases of which were operated on and 3 cases of which were not operated on. Forty-three patients were treated with sunitinib after palliative nephrectomy, 9 patients were treated with pazopanib, 3 patients were treated with acitinib, and 1 patient was treated with sorafenib. Results:The operations were successfully completed in 56 patients. Four cases (7.1%) changed from laparoscopic surgery to open surgery. The operation time was (326.8±114.9)(108-589) min. Intraoperative hemorrhage was (1 435.2±1 513.4)(20-6 000) ml, intraoperative red blood cells transfusion was (1 456.7±832.8)(400-3 600) ml in 30 cases, and intraoperative plasma transfusion was (700.0±473.6)(200-1 800) ml in 15 cases. The postoperative hospital stay was (10.6±4.6)(5-26) days. The serum creatinine one week after operation was (109.5±98.7) (47-772) μmol/L. There were 46 cases (82.1%) of renal clear cell carcinoma, 7 cases (12.5%) of papillary renal cell carcinoma and 3 cases (5.4%) of unclassified renal cell carcinoma. One case was WHO/ISUP 2016 nuclear grade 1 (1.8%), 20 cases(36.4%) was grade 2, 18 cases(32.7%)was grade 3, and 16 cases(29.1%)was grade 4. Early postoperative complications occurred in 22 cases (39.3%). Among them, 1 case of Clavien gradeⅠ was wound infection. There were 16 cases with Clavien gradeⅡ, including 5 cases who received blood transfusion due to anemia, 3 cases with chylous fistula, 4 cases with postoperative pulmonary infection, 2 cases with postoperative lower extremity venous thrombosis, 1 case with atrial fibrillation and 1 case with epididymitis. Clavien gradeⅢ a was found in 1 case with pneumothorax. Clavien gradeⅣ was found in 2 cases, including 1 case of acute cerebral infarction and 1 case of renal insufficiency.There were 2 cases with Clavien gradeⅤ with perioperative death. Among the 56 patients, 5 lost the follow-up, 2 died during the perioperative period, and the other 49 patients were followed up for 1-39 months, with a median follow-up of 14 months. The mean survival time was (25.6±2.5) months, and the median survival time was 25 months.Conclusions:It was relatively safe and effective to perform cytoreductive nephrectomy and tumor thrombectomy in patients with metastatic renal cancer with tumor thrombus. For the patients with clinical symptoms, IMDC prognosis score model medium risk group, and strong desire for surgery, the combination of cytoreductive nephrectomy with tumor thrombectomy and postoperative targeted medical therapy was recommended.

Objective According to the clinical medicinal crystal form———form γ of levonorgestrel, to establish the quantitative analysis method for levonorgestrel form γ by powder X-ray diffraction (PXRD) . Methods Firstly, single crystal X-ray diffractometry and powder X-ray diffractometry were used to confirm that the prepared levonorgestrel form γ was 100％ polymorphic purity, which provided a standard sample for quantitative analysis by single peak method; then, the standard samples of different quality levonorgestrel form γ for powder X-ray diffraction were weighed, the peak intensity values of characteristic diffraction peaks d = 6.4 , d = 6. 1  and d = 5. 6  of form γ as quantitative parameters selected, a linear relationship between the peak intensity value and the quality of form γ was established; finally, the content of levonorgestrel form γ was quantitatively analyzed. Results The peak intensity values of characteristic diffraction peaks d = 6.4 , d = 6.1  and d = 5.6  of levonorgestrel form γ and the quality showed a good linear relationship.In the range of form γ masses of 5 mg to 50 mg, the regression linear equations wereY = 459.59X+5 536.5, R2 = 0.993 0, Y = 430.03X+6 867.6, R2 = 0.990 5,Y = 615.95X+ 6 209.5, R2 = 0.990 8,respectively. Conclusion The method is simple, rapid, accurate and reliable, it can be used as quality control method for levonorgestrel polymorphs.

Objective To explore the efficacy of moderate dose bromocriptine by one-off oral administration in treatment of patients with non-acute prolactin (PRL) type pituitary adenoma.Methods Forty-three patients with definite diagnosis of non-acute prolactin type pituitary adenoma,admitted to our hospital from January 2016 to December 2017,were chosen in our study.All patients were administrated with 5 mg bromocriptine at 18 pm;the serum PRL levels were examined at 2,3 and 12 h after bromocriptine administration.The curative effects of these patients were judged by decline rate of PRL,and the curative effects of patients with different genders,different initial PRL levels and different ages were compared.Results In these 43 patients,bromocriptine showed excellent effect in 20 patients,obvious effect in 18 and invalid effect in 5.There were statistically significant differences in the efficacy of bromocriptine between different genders (P＜0.05).There were statistically significant differences in efficacy of patients with different genders after taking bromocriptine (P＜0.05).The female patients had obviously higher rate of obvious effect than the male patients.Patients with different initial PRL values had statistically significant differences in efficacy after taking bromocriptine (P＜0.05).Patients with PRL initial value of 40-200 ng/mL had significantly higher rate of obvious effect than patients with PRL initial value of ＞200 ng/mL.There was no significant difference in efficacy between patients ＜ 45 years old and patients＞45 years old (P＞0.05).Conclusion The treatment ofhyperprolactin caused by prolactin type pituitary adenoma with moderate dose bromocriptine by one-off oral administration is effective;female patients have obviously better effect than male patients;and for patients with initial prolactin＞200 ng/mL,the effect is better.

Objective To investigate the status quo of nurses' comfort about physical touch and to analyze the influencing factors.Methods Totally 398 nurses were selected during March to May 2017 from three tertiary hospitals in Tianjin with convenience sampling.General information questionnaire,Maslach Burnout Inventory General Survey (MBI-GS),and Nurses' Comfort with Touch Scale (NCTS) were used to collect data and analyze influencing factors.Results The score of nurses' comfort with touch was (44.18±6.27).The average score of nurses' comfort was (5.84±1.43) in task-oriented contact dimension,higher than scores of the other three dimensions.Multiple linear regression analysis indicated that age and emotional exhaustion were main influencing factors.Conclusion The nurses' comfort with touch was at a moderate level.Nurses aged between 25 and 46 years,with emotional exhaustion scored less than 27,had higher comfort with touch.

Objective To explore prevention and treatment of complications following resection of pineal lesions via the modified Poppen approach.Methods From January 2008 to December 2017,62 patients received resection of pineal region lesions via the modified Poppen approach at Department of Neurosurgery,Anhui Provincial Hospital.Their clinical data and outcomes were reviewed.The incidences of postoperative complications were compared between the patients with differences in lesion diameter,tentorial angle and preoperative hydrocephalus.Results Of this cohort,total tumor resection was performed in 48,subtotal resection in 10 and partial resection in 4.Follow-ups from 3 to 12 months revealed 2 cases of hemianopia which were recovered 3 months later,7 cases of occipital lobe contusion,2 cases of monoparesis and 2 cases of intracranial infection.Of the 7 cases of occipital lobe contusion,3 had intracranial hematoma which had been removed by secondary surgery and 4 had ataxia.The incidences of postoperative hemianopia and monoparesis for the patients with a lesion ＞4.5 cm in diameter were significantly higher than for those with a lesion ≤4.5 cm in diameter (P＜0.05).The incidence of postoperative hemianopia for the patients with a tentorial angle ＞60° was significantly higher than for those with a tentorial angle ≤ 60° (P＜0.05).Conclusions Size and tentorial angle of the lesion may be closely associated with the complications following resection of pineal lesions via the modified Poppen approach.The key to reducing the postoperative complications lies in comprehensive preoperative assessments,familiarity with clinical anatomy of the Poppen approach,sophisticated surgical skills and an individualized surgical protocol.

Background Diabetic macular edema (DME) is one of serious ocular complications of diabetes mellitus and is often treated by laser photocoagulation,peribulbar injection of triamcinolone acetonide (TA) and intravitreal injection of ranibizumab.However,some adverse responses occur in each approach.To seek a safe,effective and ecnomic therapy for DME is of clinical significance.Objective This study was to observe the safety and efficacy of post-sclera injection of TA with a self-made innovative device for DME and compare the outcome with peribulbar injection of TA and the intravitreal injection of ranibizumab.Methods A prospective non-randomized controlled study was performed.This study protocol was approved by Ethic Committee of Southwest Hospital of Third Military Medical University and complied with Helsinki declaration.Written informed consent was obtained from each patient before any medical treatment.Sixty eyes of 60 patients with DME were included in Southwest Hospital of Third Military Medical University from March 2013 to July 2016.The eyes were divided into post-sclera injection group,peribulbar injection group and intravitreal injection group,with 20 eyes for each group.TA at the dose of 20 mg was injected via posterior sclera with a self-made divice in the post-sclera injection group and via periphery of eyeball in the peribulbar injection group,and 0.5 mg ranibizumab was intravitreally injected in the intravitreal injection group.Best corrected visual acuity (BCVA) was examined and retinal thickness at macular area was measured by OCT in 1 month and 3 months after injection respectively.The outcome and complication were grouply compared.Results The BCVA was significantly improved 1 month and 3 months after injection in comparison with before injection in the post-sclera injection group and intravitreal injection group,and BCVA in the post-sclera injection group and intravitreal injection group was superior to that in the peribulbar injection group (all at P =0.000).No significant difference was found in post-injected BCVA between post-sclera injection group and intravitreal injection group (P =0.244,0.397).Retinal edema at macular area was gradually disappeared in the post-sclera injection group and intravitreal injection group and that in the peribulbar injection group was still visible after injection.The retinal thickness at macula was (321.85±31.98),(382.75±39.28) and (315.75 ± 40.43) μm at 1 month and was (311.95±32.73),(393.65±33.84) and (302.65±38.99) μm at 3 months after injection in the post-sclera injection group,peribulbar injection group and intravitreal injection group respectively,and the retinal thickness values at macula in the post-sclera injection group and intravitreal injection group were significantly lower than those in the peribulbar injection group (all at P =0.000).The decrease rate of retinal thickness was higher in the post-sclera injection group and intravitreal injection group than that in the peribulbar injection group at various time points after injection (all at P＜0.01).Conclusions The efficacy and safety of post-sclera injection of TA for DME are similar to intravitreal injection of ranibizumab,which are superior to peribulbar injection of TA.

Objective To study polymorphism of the free radical scavenger edaravone and to find the one which has good advantages to the clinical medication. Methods Preparation of four forms of edaravone through kinds of physical or chemical methods. These polymorphs were characterized by single crystal X-ray diffraction method (SXRD), powder X-ray diffraction method (PXRD), differential scanning calorimetry method (DSC), infrared spectrum method (IR) and melting point method (MP);a variety of influence factors experiment were used to research the stability of polymorphs. Solid edaravone in different forms were orally administered to SD rats respectively, the plasma concentration of the drug was determined by HPLC, and the pharmacokinetic characteristic of different forms was compared according to the HPLC results. Results Four forms(form A, form B, form C, form D) and the preparation of pure crystal forms were obtained by crystal screening technology. These polymorphs were identified by PXRD, DSC and IR. The edaravone polymorphs have an influence on the stability and pharmacokinetic. Conclusion Edaravone research provideds a variety of crystal material composition, preparation methods, stability, solubility and pharmacokinetic characteristic, and form A has been proved of good advantage one. This research provides data and technology support for choice of preponderant pharmaceutical polymorphs and drug quality standard improvement.

Based on the professional characteristics and nature of ophthalmology special examination and combined with teaching requirements for optometry foreign students, we developed a targeted teaching plan and practiced the classification teaching. Using guided trilogy teaching, we guided students to identify and analyze the similarities and differences between the image and the special examination function exami-nation results, emphasizing the cultivation of clinical ophthalmology diagnostic thinking of students, and we obtained good teaching and practice effect.