Objective: To explore the method and effect of endoscopic assisted functional rhinoplasty for patients with deviated nose and deviated nasal septum, which achieve correction of nasal morphology and ventilation dysfunction. Methods: The clinical data of 226 patients with deviated nose and deviated nasal septum from June 2009 to February 2022 who were treated by endoscopic assisted functional rhinoplasty in the Affiliated Hospital of Qingdao University were analyzed retrospectively. There were 174 males and 52 females, with the age ranging from 7 to 67 years old. The effect was evaluated by subjective and objective evaluation methods. SPSS 27.0 software was used for statistical analysis. Results: All patients were followed up for 6 to 24 months, 174 cases were cured (174/226, 76.99%), 52 cases were effective (52/226, 23.01%), and the total effective rate was 100% (226/226). The difference between preoperative and postoperative facial appearance deviation was statistically significant ((6.84±2.25)mm vs (1.82±1.05)mm, t=38.94, P<0.001), and the nasal ventilation function of all patients was improved. Conclusions: Endoscopic assisted functional rhinoplasty for the patients with deviated nose combined with deviated nasal septum has the advantages of clear surgical field, fewer complications, and good result. It can achieve the purpose of simultaneous correction of nasal and ventilation dysfunction, which is recommended for popularizing in clinical application.

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34βE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34βE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.
Humans ; Male ; Biomarkers, Tumor/genetics* ; Carcinoma, Renal Cell/pathology* ; Chromosome Aberrations ; Kidney Neoplasms/pathology* ; Molecular Biology ; Mutation ; Prognosis

Aim To investigate the pharmacological effects of paeonol as a formyl peptide receptor activator on rheumatoid arthritis (HA).Methods The target rlataset was obtained from the high throughput Gene Expression Database ( GEO) , and multiple data sets were combined by USING R language to explore three groups of macrophage differentially expressed genes ( DEGs) in untreated,lipopolysaccharide (LPS) treat¬ment and paeonol and LPS treatment, and their enrich-ment pathway was analyzed.Protein-protein interaction (PPI) networks were constructed in the STRING data¬base anrl visualized in Cytoscape software.The inhibi¬tor}' effect of Hub gene formyl peptide receptor ( FPR) on RA inflammation was validated by TNF-cx stimula¬tion of fibroblast synovial cells ( FLS).Results Through bioinformatics analysis, 169 differential genes ( DEGs) related to inflammation and 275 DEGs related to the mechanism of paeonol action were obtained.Combined analysis of the two groups of DEGs showed that FPR played a key role in the anti-inflammatory mechanism of paeonol.Further studies on the mecha¬nism of paeonol showed that paeonol activated FPR, and the inhibitory effect of paeonol on FLS inflamma¬tion was rescued by TRP-ARg-TRP-TRP-TRP-TRP- TRP-TRP-NH2 (WRW4).Conclusion Paeonol can inhibit the inflammatory development of RA through the FPR pathway.

Aim To investigate the effectiveness and safety of alfentanil in general anesthesia.Methods In this study, a multicenter randomized double-blind con¬trolled study was conducted.A total of 352 subjects were selected and randomly assigned to fentanyl group (group A, n =176) and alfentanil group (group 15, n = 176).Anesthesia induction: intravenous midazolam 0.03 mg • kg-1 + fentanyl 25 p.g • kg"'(group A) or alfentanil 4 p,g • kg-1 ( group 15) + propofol 2 mg • kg"1 + rocuronium 0.8 mg • kg"1.Sevoflurane + fent¬anyl ( group A ) or alfentanil ( group B ) + rocuronium were used for anesthesia.The vital signs of patients re¬covery time and extuhation time, anesthesia-related complications and the use of related remedial drugs during anesthesia induction and maintenance were compared between the two groups.Results During the induction and maintenance period of anesthesia, alfentanil and fentanyl could equally effectively inhibit the stress response induced by endotracheal intubation and surgical stimulation.Alfentanil also showed more effective inhibition on stress response induced by endo¬tracheal intubation and surgical stimulation than that of fentanyl ( P < 0.05 ) .However, there was no signifi¬cant difference in the incidence of intraoperative hypo¬tension and hypertension and the time of anesthesia re¬covery and extubation between the two groups.Conclu¬sions Both alfentanil and fentanyl can effectively in¬hibit the stress response induced by surgical stimulation and could be safely used in general anesthesia in sur¬gery.Alfentanil has more advantages in maintaining the stability of blood pressure and heart rate during an¬esthesia induction and maintenance.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, which is safe at therapeutic doses but can cause severe liver injury and even liver failure after overdoses. The mouse model of APAP hepatotoxicity recapitulates closely the human pathophysiology. As a result, this clinically relevant model is frequently used to study mechanisms of drug-induced liver injury and even more so to test potential therapeutic interventions. However, the complexity of the model requires a thorough understanding of the pathophysiology to obtain valid results and mechanistic information that is translatable to the clinic. However, many studies using this model are flawed, which jeopardizes the scientific and clinical relevance. The purpose of this review is to provide a framework of the model where mechanistically sound and clinically relevant data can be obtained. The discussion provides insight into the injury mechanisms and how to study it including the critical roles of drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy and the sterile inflammatory response. In addition, the most frequently made mistakes when using this model are discussed. Thus, considering these recommendations when studying APAP hepatotoxicity will facilitate the discovery of more clinically relevant interventions.

Acetaminophen (APAP) overdose can induce liver injury and is the most frequent cause of acute liver failure in the United States. We investigated the role of p62/SQSTM1 (referred to as p62) in APAP-induced liver injury (AILI) in mice. We found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment, which was inversely correlated with the hepatic levels of APAP-adducts. APAP also activated mTOR at 24 h, which is associated with increased cell proliferation. In contrast, p62 knockout (KO) mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOR activation and cell proliferation with aggravated liver injury at 24 h after APAP treatment. Surprisingly, p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 h. We found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor (VWF) and platelet aggregation, which are associated with increased cell proliferation and improved liver injury at 48 h after APAP treatment. Our data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.

OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.

Monoclonal antibodies (mAbs) have been widely used as therapeutic drugs for treating diseases such as cancers and auto-immune diseases. When using an IgG4 isotype, one of the challenges is the instability of its hinge which is prone to Fab-arm exchange (FAE). The hinge sequence of a wild type IgG4 is -CPSC-, however, a single point mutation S228P from -CPSC- to -CPPC- can effectively diminish FAE, thereby improving hinge stability of the IgG4 molecule. Sintilimab is the fully human anti-PD-1 monoclonal antibody designed and developed for immuno-oncology, in which serine 228 in the hinge was engineered to proline to mitigate FAE. In this study, LC-MS is used to study hinge stability of sintilimab in both in vitro (PBS and human serum) and in vivo (SCID mouse) studies. The studies demonstrate that LC-MS is a fast and simple way to monitor for the occurrence of FAE in vitro and in vivo, and FAE can be eliminated by antibody engineering with a single point mutation.

Objective: To compare the time and spatial distribution of hepatitis C and HIV/AIDS cases and its correlation, in China from 2012 to 2017. Methods: Data on reported hepatitis C and HIV/AIDS cases was gathered from the Direct Reporting System of Infectious Diseases Information Network in China, 2012 to 2017 while annually collected provincial data was based on the date of review and current address. Correlation of the data was analyzed, using both simple correlation and linear regression methods. Results: The number of reported cases of hepatitis C remained stable in China, in 2012-2017, with the number of annual reported cases as 201 622, 203 155, 202 803, 207 897, 206 832 and 214 023, respectively. The number of reported cases on HIV/AIDS showed a steady growing trend, from 82 434, 90 119, 103 501, 115 465, 124 555 to 134 512. However, the numbers of hepatitis C and HIV/AIDS cases were in the same, top six provinces: Henan, Guangdong, Xinjiang, Guangxi, Hunan and Yunnan. Results from the simple correlation analysis indicated that there was a positive correlation (r>0.5, P<0.01) existed between the above-said two kinds of cases at the provincial level in China, in 2012-2017. Again, results from the linear regression analysis also showed that the correlation coefficient r(s) and year was strongly correlated (r=0.966) while r(s) had been linearly increasing with time. Conclusions: Our data showed that there were temporal and spatial correlations existed between the reported cases of hepatitis C and HIV/AIDS at the provincial level, suggesting that relevant prevention and control programs be carried out in areas with serious epidemics. Combination of the two strategies should be encouraged, especially on prevention and treatment measures related to blood transmission.
Age Distribution ; China/epidemiology* ; Epidemics ; HIV ; HIV Infections/ethnology* ; Hepatitis C/ethnology* ; Humans ; Linear Models ; Spatial Analysis ; Spatio-Temporal Analysis ; Young Adult

The aim of this study is to evaluate the effectiveness and safety of China Savin pollen extract which was used for skin prick test (SPT) in the diagnosis of China Savin pollen allergy. Patients with diagnosis of allergic diseases were collected from Allergy Department of Peking Union Medical College Hospital. All patients were given SPT with China Savin pollen extract, and the mean wheal diameter (MWD) was measured after 15 minutes. Receiver operating characteristic curve (ROC) analysis was performed based on the results of serum specific immunoglobulin E (sIgE). The effectiveness of SPT in the diagnosis of China Savin pollen allergy was evaluated under different diagnostic cutoff values. Adverse events were also recorded to evaluate the safety. A total of 1 029 patients were enrolled in this study without drop out case. There were 1 007 patients in full analysis set (FAS) and 765 patients in per protocol analysis set (PPS). The elimination rate was 25.66%. The area under the ROC curve of FAS is 0.814 (95%: 0.788-0.839); which of PPS is 0.829 (95%: 0.801-0.857). Based on the ROC curve of PPS, the optimal and the 95% specificity diagnostic cutoff values of MWD were 3.25 mm and 4.75 mm respectively. Based on different diagnostic cutoff value (3.00, 3.25 and 4.75 mm), the sensitivities of SPT with China Savin pollen extract were 0.740 0 (95%: 0.701 6-0.778 4), 0.700 (95%: 0.659 8-0.740 2) and 0.532 (95%: 0.488 3-0.575 7) respectively, whereas the specificity was gradually increased in sequence, which was 0.769 8 (95%: 0.719 1-0.820 5), 0.826 4 (95%: 0.780 8-0.872 0) and 0.950 9 (95%: 0.924 9-0.976 9) respectively. There were 7 adverse events observed among 6 patients (rate: 0.583%, 6/1 029). The manifestation was mild. There was no severe adverse event. SPT with China Savin pollen extract is an effective and safe tool for the diagnosis of China Savin pollen allergy. The effectiveness of diagnosis could be improved based on integration of medical history and different diagnostic threshold values of SPT.
Allergens ; adverse effects ; China ; Humans ; Immunoglobulin E ; Pollen ; adverse effects ; Rhinitis, Allergic, Seasonal ; diagnosis ; Skin Tests