OBJECTIVE To explore the protective effect and mechanism of Longshengzhi capsules on cerebral ischemia- reperfusion injury in rats. METHODS The model of middle cerebral artery occlusion （MCAO） was established by using the improved thread occlusion method. The experiment was divided into six groups： sham surgery group （only separating blood vessels without inserting thread plugs， given the same volume of normal saline）， model group （modeling， given the same volume of normal saline）， nimodipine group （positive control， modeling， dose of 20 mg/kg）， and low-dose， medium-dose， and high-dose groups of Longshengzhi capsules （modeling， doses of 0.72， 1.44 and 2.88 g/kg， respectively）， with 10 mice in each group. Each group was given corresponding medication solution/normal saline by gavage， once a day， for 7 consecutive days. One hour after the last administration， the Zea Longa scoring method was used to score the neurological deficits in each group of rats， and the ABC enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rats； TTC staining was used to observe the volume of cerebral infarction in rats and calculate the cerebral infarction volume ratio. Hematoxylin eosin staining was used to observe the pathological changes in the brain tissue of rats. Immunohistochemical staining was used to detect the positive expression of NLRP3 protein in the brain tissue of rats. Real-time fluorescence quantitative PCR was used to detect mRNA relative expressions of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the brain tissue of rats. Western blot assay was adopted to detect the relative expressions of TLR4， NLRP3 and phosphorylated NF-κB （p-NF-κB） protein in the brain tissue of rats and its intracellular NF-κB protein. RESULTS Compared with the sham surgery group， the neural dysfunction score， serum levels of TNF-α and IL-6， cerebral infarction volume ratio， relative expression levels of NF-κB and TLR4 mRNA， as well as protein relative expressions of TLR4， NLRP3 and p-NF-κB in the brain tissue， and relative protein expression of intracellular NF-κB were increased significantly in the model group （P＜0.01）； the enlarged gap and significant edema were observed in cortical nerve cells of brain tissue in rats， with a large amount of inflammatory cell infiltration； the positive expression of NLRP3 protein in brain tissue of rats obviously increased. Compared with the model group， the levels of the above indicators in the medium-dose and high-dose groups of Longshengzhi capsules， as well as the Nimodipine group， were reversed to varying degrees， and most differences were statistically significant （P＜0.05 or P＜0.01）； the pathological morphology observation showed a significant improvement， and the positive expression of NLRP3 protein in the brain tissue of rats was obviously reduced. CONCLUSIONS Longshengzhi capsules may inhibit TLR4/NF-κB/NLRP3 signaling pathway and neuroinflammatory response， thereby achieving a protective effect against cerebral ischemia-reperfusion injury in rats.

Objective:To investigate the correlations between subjective nasal patency, nasal valve area size and aerodynamic parameters in normal nasal cavity by means of numerical simulation, and to explore the effect of nasal valve on nasal subjective sensation and nasal airflow regulation.Methods:A total of 52 healthy participants (31 males and 21 females) with the average age of 37.8 years, were recruited from the outpatient Department of Otorhinolaryngology Head and Neck Surgery, the Ninth People′s Hospital Affiliated to the Medical College of Shanghai Jiao Tong University between January and August 2023. Visual Analog Scale (VAS) scores for unilateral nasal subjective sensation were obtained from all participants. Additionally, the aerodynamic characteristics of inspiratory airflow were simulated. A correlation matrix analysis was conducted to identify the correlation strength between these subjective and objective parameters.Results:VAS scores showed negative correlations with unilateral nasal valve cross-sectional area ( r=-0.85, P<0.01) and unilateral intranasal airflow ( r=-0.57, P<0.01), and was a positive correlation with unilateral nasal resistance (NR) at the front-end of inferior turbinate ( r=0.61, P<0.01). The average cross-sectional area of unilateral nasal valve was (0.85±0.35) cm 2. The cross-sectional area of unilateral nasal valve was negatively correlated with unilateral NR ( r=-0.50, P<0.01), and positively correlated with unilateral nasal airflow ( r=0.61, P<0.01). The NR at the nasal valve area accounted for (40.41±23.54)% of the total unilateral NR. Nearly half of the unilateral NR [(46.74±21.38)%] and air warming [(49.96±10.02)%] occurring before the front end of inferior turbinate were achieved. Conclusions:The nasal valve area plays a crucial role in influencing nasal NR, unilateral nasal airflow, and changes in nasal airflow temperature. Moreover, it is associated with subjective perception of nasal patency.

Objective:To study the influencing factors of thyroid diseases among residents in a coastal area, Dongtai City, and provide scientific basis for further prevention and control of thyroid diseases.Methods:Thyroid disease patients of Dongtai City in the coastal area diagnosed by Dongtai People's Hospital from January to December 2019 were selected as the survey subjects, and diagnosis of various diseases and their gender and age distribution were analyzed. In the case-control study, confirmed new cases were selected as the case group, and healthy individuals matched 1∶1 by village group, gender, and age as the control group. A questionnaire survey and related examinations such as urinary iodine test and thyroid ultrasound examination were conducted. The survey results were summarized and analyzed (Wilcoxon rank sum test, conditional logistic regression multivariate analysis).Results:(1) A total of 3 508 patients with thyroid diseases were diagnosed, accounting for 319.46/100 000 of the total population, including 2 616 female patients, accounting for 74.57%; 2 824 cases aged 30 to 69 years old, accounting for 80.50%; 1 539 cases of hyperthyroidism, accounting for 43.87%; and 961 cases of hypothyroidism, accounting for 27.39%. (2) A total of 984 cases were surveyed in a 1∶1 paired manner. Multivariate analysis showed that the risk factors for thyroid diseases included monthly average income, family history, related surgeries, personality, working pressure, interpersonal relationships, and urinary iodine grading ( P < 0.05). The risk factors for hyperthyroidism included occupation, family history of hyperthyroidism, personality, family financial pressure, and interpersonal relationships ( P < 0.05), while the risk factor for goiter included urinary iodine grading ( P = 0.008). Conclusions:The occurrence of thyroid diseases in a coastal area, Dongtai City, may be related to family history, gender, age, personality, and working pressure. There is a correlation between goiter and low iodine nutrition level, which further confirms the correctness of the strategy of salt iodization in preventing and treating iodine deficiency disorders in coastal areas.

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 evaluate the effect of surgical revision of nasofacial deformity secondary to maxillary frontal process fracture.Methods:The clinical data of patients with nasofacial deformities secondary to maxillary frontal process fractures who underwent surgery in the Department of Otolaryngology, Head and Neck Surgery of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2009 to December 2020 were retrospectively analyzed. The nasofacial deformity was surgically treated by open reduction with internal fixation, nasal septum correction, and reconstruction of orbital wall fracture. Three months after surgery, the surgical results were evaluated from the following three aspects. (1) Nasofacial morphology, which was evaluated by two doctors and the patient, and was classified into 3 levels: very satisfied, satisfied, and unsatisfied. (2) Objective assessment of nasal ventilation function, which was measured by nasal acoustic rhinometry and nasal resistance detection, including measurements of nasal minimum cross-sectional area (MCA), nasal volume 7 cm from the anterior nostril (NV), total nasal inspiratory resistance (TRi) and total nasal expiratory resistance (TRe). To eliminate the differences caused by swelling of the nasal mucosa, the patients were divided into 3 groups of <7 d, 7-14 d, and >14 d according to the time from trauma to preoperative examination for pre- and post-operative comparisons, respectively. (3) Subjective assessment of nasal ventilation function was performed using the nasal obstructive symptom evaluation (NOSE) scale, with a total score of 0 to 20, with a higher score indicating more severe nasal obstruction symptoms. The SPSS 17.0 software was used for statistical analysis, and the measurement data were expressed as Mean±SD. A paired t-test was used to compare the preoperative and 3-month postoperative data, with P<0.05 indicating a statistically significant difference. Results:A total of 83 patients were included, 53 males and 30 females, aged 7 to 78 years, with a median of 35 years. All patients underwent successful surgery, and all soft tissue incisions healed well after surgery with improved nasofacial morphology. Three months after surgery, the physicians were very satisfied and satisfied with the nasofacial morphology in 49 (59%) and 34 (41%) patients, respectively, and patients were very satisfied, satisfied, and unsatisfied in 51 (61%), 29 (35%), and 3(4%) cases, respectively. Before surgery, the <7 d group (14 cases), 7-14 d group (28 cases), and >14 d group (41 cases) had MCA values of (0.43±0.10) cm 2, (0.51±0.15) cm 2, and (0.50±0.14) cm 2; NV values of (9.76±2.20) cm 3, (12.40±4.15) cm 3, and (12.40±3.87) cm 3; TRi values of (1.93±0.28) kPa·L -1·s -1, (1.96±0.24) kPa·L -1·s -1, and (1.96±0.23) kPa·L -1·s -1; TRe values of (2.02±0.35) kPa·L -1·s -1, (2.08±0.38) kPa·L -1·s -1, and (2.08±0.34) kPa·L -1·s -1, respectively. Three months after surgery, in the three groups, the MCA values were (0.48±0.08) cm 2, (0.56±0.15) cm 2, and (0.56±0.14) cm 2; the NV values were (11.56±2.49) cm 3, (14.40±4.50) cm 3, and (14.41±4.24) cm 3; the TRi values were (1.74±0.19) kPa·L -1·s -1, (1.78±0.15) kPa·L -1·s -1, (1.78±0.14) kPa·L -1·s -1; the TRe values were (1.73±0.24) kPa·L -1·s -1, (1.79±0.24) kPa·L -1·s -1, and (1.79±0.22) kPa·L -1·s -1, respectively. In all three groups, the MCA and NV values at 3 months postoperatively were greater than the preoperative values of MCA and NV (all P < 0.01), and the TRe and TRi values at 3 months postoperatively were less than those preoperative values (all P < 0.01). At 3 months postoperatively, the NOSE scale score was (4.1±1.2)points, which was significantly lower than the preoperative score of NOSE scale score[(10.5±1.8)points] ( P<0.01). Conclusion:The combination of objective and subjective assessment method can help the surgeon to accurately determine the nasofacial morphological and functional defects caused by the fracture of the maxillary frontal process area before surgery and to formulate a perfect surgical plan. The patients’ nasofacial appearance and nasal ventilation functions were significantly improved after the fracture revision surgery.

Objective:To evaluate the effect of surgical revision of nasofacial deformity secondary to maxillary frontal process fracture.Methods:The clinical data of patients with nasofacial deformities secondary to maxillary frontal process fractures who underwent surgery in the Department of Otolaryngology, Head and Neck Surgery of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2009 to December 2020 were retrospectively analyzed. The nasofacial deformity was surgically treated by open reduction with internal fixation, nasal septum correction, and reconstruction of orbital wall fracture. Three months after surgery, the surgical results were evaluated from the following three aspects. (1) Nasofacial morphology, which was evaluated by two doctors and the patient, and was classified into 3 levels: very satisfied, satisfied, and unsatisfied. (2) Objective assessment of nasal ventilation function, which was measured by nasal acoustic rhinometry and nasal resistance detection, including measurements of nasal minimum cross-sectional area (MCA), nasal volume 7 cm from the anterior nostril (NV), total nasal inspiratory resistance (TRi) and total nasal expiratory resistance (TRe). To eliminate the differences caused by swelling of the nasal mucosa, the patients were divided into 3 groups of <7 d, 7-14 d, and >14 d according to the time from trauma to preoperative examination for pre- and post-operative comparisons, respectively. (3) Subjective assessment of nasal ventilation function was performed using the nasal obstructive symptom evaluation (NOSE) scale, with a total score of 0 to 20, with a higher score indicating more severe nasal obstruction symptoms. The SPSS 17.0 software was used for statistical analysis, and the measurement data were expressed as Mean±SD. A paired t-test was used to compare the preoperative and 3-month postoperative data, with P<0.05 indicating a statistically significant difference. Results:A total of 83 patients were included, 53 males and 30 females, aged 7 to 78 years, with a median of 35 years. All patients underwent successful surgery, and all soft tissue incisions healed well after surgery with improved nasofacial morphology. Three months after surgery, the physicians were very satisfied and satisfied with the nasofacial morphology in 49 (59%) and 34 (41%) patients, respectively, and patients were very satisfied, satisfied, and unsatisfied in 51 (61%), 29 (35%), and 3(4%) cases, respectively. Before surgery, the <7 d group (14 cases), 7-14 d group (28 cases), and >14 d group (41 cases) had MCA values of (0.43±0.10) cm 2, (0.51±0.15) cm 2, and (0.50±0.14) cm 2; NV values of (9.76±2.20) cm 3, (12.40±4.15) cm 3, and (12.40±3.87) cm 3; TRi values of (1.93±0.28) kPa·L -1·s -1, (1.96±0.24) kPa·L -1·s -1, and (1.96±0.23) kPa·L -1·s -1; TRe values of (2.02±0.35) kPa·L -1·s -1, (2.08±0.38) kPa·L -1·s -1, and (2.08±0.34) kPa·L -1·s -1, respectively. Three months after surgery, in the three groups, the MCA values were (0.48±0.08) cm 2, (0.56±0.15) cm 2, and (0.56±0.14) cm 2; the NV values were (11.56±2.49) cm 3, (14.40±4.50) cm 3, and (14.41±4.24) cm 3; the TRi values were (1.74±0.19) kPa·L -1·s -1, (1.78±0.15) kPa·L -1·s -1, (1.78±0.14) kPa·L -1·s -1; the TRe values were (1.73±0.24) kPa·L -1·s -1, (1.79±0.24) kPa·L -1·s -1, and (1.79±0.22) kPa·L -1·s -1, respectively. In all three groups, the MCA and NV values at 3 months postoperatively were greater than the preoperative values of MCA and NV (all P < 0.01), and the TRe and TRi values at 3 months postoperatively were less than those preoperative values (all P < 0.01). At 3 months postoperatively, the NOSE scale score was (4.1±1.2)points, which was significantly lower than the preoperative score of NOSE scale score[(10.5±1.8)points] ( P<0.01). Conclusion:The combination of objective and subjective assessment method can help the surgeon to accurately determine the nasofacial morphological and functional defects caused by the fracture of the maxillary frontal process area before surgery and to formulate a perfect surgical plan. The patients’ nasofacial appearance and nasal ventilation functions were significantly improved after the fracture revision surgery.

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

Objective:To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT.Methods:Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia.Results:A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95% CI 23.0%-70.6%) , 41.8% (95% CI 17.3%-64.9%) , 8.8% (95% CI 2.9%-26.4%) , and 51.1% (95% CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95% CI 12.7%-73.5%) and 75.0% (95% CI 51.4% -88.8%) ( P=0.017) , respectively. Conclusion:CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

Objective:To investigate the application and clinical outcomes of using 3D computer-assisted printing technique combined with plastic titanium mesh in the reconstruction of maxillary defect.Methods:Clinical data of 14 patients in Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People′s Hospital from January 2016 to June 2018, who were treated for partial or total removal of the maxilla due to benign or malignant tumors and those acquired maxillary defects caused by severe compound trauma were analyzed retrospectively. Twelve males and 2 females were included, with the age ranging from 16 to 51 years old. The sinonasal malignant tumors included squamous carcinoma ( n=2) while benign tumors included hemangioma ( n=1), maxillary fibrous dysplasia ( n=3), maxillary cyst ( n=2) and giant cell tumor of the maxilla ( n=1). Five cases of post-traumatic maxillary defect were also included. According to preoperative thin-layer CT scanning data, computer modeling data was transmitted to a 3D printer to print out the original model and the reconstructed model. Preoperative simulation of tumor removal and maxillary reconstruction was done on the patient′s original model, and the titanium mesh was shaped on the reconstructed model in order to properly reconstruct the area needed to be repaired. The pre-made titanium mesh was implanted into the defect area, the soft tissue flaps were reset, layered stitching and the local pressured bandage were used after surgery. Through postoperative clinical and CT examination, the patient′s maxillofacial shape, nasal function and complications were evaluated. The results were analyzed by descriptive statistical method. Results:Lesions could be completely removed within the predicted range on the preoperative 3D-printed models of all cases. After debridement, titanium mesh could be implanted easily without re-shaping and trimming during surgery as in trauma cases. Titanium mesh could completely cover the missing bone surface closely, with titanium nails fixed smoothly, and the implanted titanium mesh was solid and stable. After the follow-up of 6 to 20 months, all patients were satisfied with the facial symmetry and the function was recovered well.Conclusion:Using 3D computer-assisted printing technique combined with plastic titanium mesh in the reconstruction of maxillary defect can accurately restore the maxillary structure for soft tissue support, and restore the facial shape and function.

Objective:To investigate the effect of nasal septum perforation (SP) with different locations and sizes on nasal airflow by means of numerical simulation.Methods:Two healthy persons with normal nasal anatomy were enrolled in this study, including a 45 years old male (case 1) and a 36 years old female (case 2). Nasal CT data was used as the basis to create nasal airway numerical models of nasal SP with different locations (anterior caudal, central caudal, posterior caudal and anterior cranial) and sizes (diameter of 10 mm and 5 mm respectively). The inspiratory airflow characteristics (nasal cavity volume, nasal cavity wall area, pressure, nasal resistance, temperature, airflow velocity, wall shear stress, airflow-rate partitioning and vortex) of these nasal airway numerical models were simulated and analyzed. Pearson correlation analysis was performed between nasal resistances, airflow temperature and nasal cavity wall area. Results:In terms of pressure and nose resistance, the anterior caudal and larger size SP lead to more obvious variation of pressure distribution, and increased nasal resistance was especially found in the nasal cavity with anterior and medium caudal SP. In terms of temperature, the anterior (caudal and cranial) and larger size SP had significant effect on local temperature gradient as same as the anterior cranial and smaller size SP. Nasal heating efficiency was lower in nasal model with the anterior and larger size SP than that in the normal model. The temperature difference from the nostril to the end of nasal septum had positive correlation with nasal cavity wall area ( R2 value of case 1 and case 2 was 0.69, 0.41, respectively, all P<0.01). In terms of airflow velocity, the anterior caudal and cranial SP had more significant effect on the average airflow velocity in the nasal cavity. The anterior and medium caudal SP could make the airflow distribution in the asymmetric bilateral nasal cavity more unbalanced compared to the bilateral symmetrical nasal models. The anterior and medium SP resulted in a more pronounced vortex distribution than the posterior SP. Conclusions:The effect of SP on nasal cavity is related to its location and size. The anterior and larger size SP shows more negative influence on intranasal pressure, nasal resistance, heat transmission efficiency, airflow-rate partitioning than the posterior and smaller size SP.