A Case of Invasive Pulmonary Aspergillosis.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a deep fungal infection caused by invasion of Aspergillus mycelium into the lung parenchyma resulting in tissue destruction and necrosis, which occurs more often in im-munosuppressed populations. The severity of the disease and the rapid progression of the lung lesions puts pa¬tients at high risk of death and poor prognosis if the correct therapeutic intervention is not given as early as possible. METHODS: Here we report a case of IPA, which was initially diagnosed as community-acquired pneumonia in a local hospital. The symptoms did not improve after receiving anti-infective treatment. The patient was diagnosed with IPA after completing a chest CT examination and an electronic bronchoscopy, as well as pathogenetic examination of the bronchoalveolar lavage fluid and pathological examination of the left bronchial mass in the respiratory department of our hospital, which was finally diagnosed as IPA. After one week of administration of voriconazole for anti-fungal infection treatment, the patient's symptoms improved significantly, and a repeat chest CT suggested that the lung lesions were better than before. In order to raise clinicians' awareness of this disease, we also conducted a literature analysis. RESULTS: The final diagnosis of IPA was made by analyzing the patient's history, symptoms, signs, and relevant findings. CONCLUSIONS: When the patient's clinical symptoms and imaging manifestations are consistent with IPA, electronic bronchoscopy and pathogenetic and pathological examinations may be appropriately performed to clarify the na-ture of the lesion. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis. Appropriate treatment should be given at an early stage.

A Case of IgG4 Related Lung Disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated systemic inflammatory fibrotic disease, which is a relatively rare and novel disease that can involve multiple organs or tissues, with variable clinical manifestations, and for which pulmonary involvement has been reported relatively infrequently. METHODS: Here we report a case of pulmonary infection that was initially suspected and received anti-inflammatory treatment, but the symptoms did not improve. CT examination indicated progression of the pulmonary lesion, and the nature of the lesion could not be determined by tracheoscopy and bronchoalveolar lavage. The diagnosis of IgG4 related lung disease (IgG4-RLD) was confirmed by percutaneous lung biopsy. A joint literature analysis was conducted to improve clinicians' understanding of this disease. RESULTS: The patient's history, symptoms, signs and relevant examination results were analyzed. The final diagnosis was IgG4-RLD. CONCLUSIONS: When the clinical symptoms and imaging manifestations of the patients are consistent with IgG4-RLD, pathological examination can be appropriately performed to clarify the nature of the lesions. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis, and proper treatment should be given at an early stage.

A Prediction Model for Prolonged Hospital Length of Stay (ProLOS) in Coronavirus Disease 2019 (COVID-19) Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the normalization of COVID-19 globally, it is crucial to construct a prediction model that enables clinicians to identify patients at risk for ProLOS based on demographics and serum inflammatory biomarkers. METHODS: The study included hospitalized patients with a confirmed diagnosis of COVID-19. These patients were randomly grouped into a training (80%) and a test (20%) cohort. The LASSO regression and ten-fold cross-validation method were applied to filter variables. The training cohort utilized multifactorial logistic regression analyses to identify the independent factors of ProLOS in COVID-19 patients. A 4-variable nomogram was created for clinical use. ROC curves were plotted, and the area under the curve (AUC) was calculated to evaluate the model's discrimination; calibration analysis was planned to assess the validity of the nomogram, and decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model. RESULTS: The results showed that among 310 patients with COVID-19, 80 had extended hospitalization (80/310). Four independent risk factors for COVID-19 patients were identified: age, coexisting chronic respiratory diseases, white blood cell count (WBC), and serum albumin (ALB). A nomogram based on these variables was created. The AUC in the training cohort was 0.808 (95% CI: 0.75 - 0.8671), and the AUC in the test cohort was 0.815 (95% CI: 0.7031 - 0.9282). The model demonstrates good calibration and can be used with threshold probabilities ranging from 0% to 100% to obtain clinical net benefits. CONCLUSIONS: A predictive model has been created to accurately predict whether the hospitalization duration of COVID-19 patients will be prolonged. This model incorporates serum WBC, ALB levels, age, and the presence of chronic respiratory system diseases.

A Case of Organizing Pneumonia Resembling Lung Cancer.

BACKGROUND: Organizing pneumonia (OP) is a pathologic diagnosis with clinical and imaging manifestations that often resemble other diseases, such as infections and cancers, which can lead to delays in diagnosis and inappropriate management of the underlying disease. In this article, we present a case of organized pneumonia that resembles lung cancer. METHODS: We report a case of initial suspicion of pulmonary malignancy, treated with anti-inflammatory medication and then reviewed with CT suggesting no improvement, and finally confirmed to be OP by pathological biopsy taken via transbronchoscopy. A joint literature analysis was performed to raise clinicians' awareness of the diagnosis and treatment of OP. RESULTS: Initially, because of the atypical auxiliary findings, we thought that the disease turned out to be a lung tumor, which was eventually confirmed as OP by pathological diagnosis. CONCLUSIONS: The diagnosis and treatment of OP requires a combination of clinical information and radiological expertise, as well as biopsy to obtain histopathological evidence. That is, clinical-imaging-pathological tripartite cooperation and comprehensive analysis.

A Case of Tuberculosis Misdiagnosed as Sarcoidosis and then Confirmed by NGS Testing.

BACKGROUND: Pulmonary tuberculosis (PTB) is an important infectious disease that threatens the health and life of human beings. In the diagnosis of PTB, imaging plays a dominant role, but due to the increasing drug resistance of Mycobacterium tuberculosis, atypical clinical manifestations, "different images with the same disease" or "different diseases with the same image" in chest imaging, and the low positivity rate of routine sputum bacteriology, which leads to a high rate of misdiagnosis of PTB. We report a case of pulmonary tuberculosis that was misdiagnosed on imaging. We report a case of pulmonary tuberculosis that resembled sarcoidosis on imaging and was negative for antacid staining on sputum smear and alveolar lavage fluid, and was later diagnosed by microbial next-generation sequencing (NGS). The case was initially misdiagnosed as sarcoidosis. METHODS: Alveolar lavage fluid NGS, chest CT, bronchoscopy. RESULTS: Chest CT showed multiple inflammatory lesions in both lungs, multiple nodular foci in both lungs, and multiple enlarged lymph nodes in the mediastinum and hilar region on both sides. Fiberoptic bronchoscopy was performed in the basal segment of the left lower lobe of the lungs to carry out bronchoalveolar lavage, and the lavage fluid was sent to the NGS test and returned the following results: Mycobacterium tuberculosis complex group detected in the number of sequences of 293. Based on the results of the NGS test, the diagnosis of pulmonary tuberculosis could be confirmed. CONCLUSIONS: The diagnosis of pulmonary tuberculosis cannot be easily excluded in patients with "different images with the same disease" or "different diseases with the same image" on chest imaging without the support of sputum positivity. The goal was to improve the alertness of medical personnel to the misdiagnosis of tuberculosis and the application of NGS technology.

CEA Negative Initial Diagnosis of HP Infection Finally Confirmed by Bronchoscopic Biopsy as Lung Adenocarcinoma.

BACKGROUND: Carcinoembryonic antigen (CEA) is a polysaccharide complex that is found in the human respiratory system. It is of significant use in disease surveillance of lung cancer; however, serum CEA can occasionally only offer little assistance. We present a case of recurring infection initially diagnosed as carcinoembryonic antigen-negative in a patient with a history of hypersensitivity pneumonitis infection, which finally led to the diagnosis of lung adenocarcinoma following percutaneous lung puncture. METHODS: Appropriate laboratory tests, chest CT, bronchoscopy, percutaneous lung puncture, and pathologic examination were performed to explore the cause of the disease. RESULTS: Because CEA was negative and a chest CT showed interstitial changes in both lungs with numerous hyperdense shadows, coupled with the patient's history of hypersensitivity pneumonitis, we initially believed that the infection was relapsing. However, a percutaneous lung puncture eventually revealed that the patient had lung adenocarcinoma. CONCLUSIONS: Vigilance needs to be increased in clinical work for patients with interstitial lung disease, low tumor markers such as CEA, and imaging suggestive of inflammatory progression, which in fact turns into lung cancer. When the treatment is ineffective after standardized application of hormone and anti-infection, lung tissue should be obtained for pathological examination in time to obtain pathological evidence.

Accidental Detection of Tuberculous Empyema at Health Check-Up.

BACKGROUND: Patients with tuberculous empyema (TE) can have a serious impact on lung function as their disease progresses, and, if left untreated, can cause damage to other parts of the body such as the thorax and spine, causing pain and inconvenience to the patient. Early diagnosis and the search for appropriate treatment are key to improving the survival rate of the disease. METHODS: We report a case of a young patient with an unexpected finding of right pleural effusion on physical examination, who was eventually diagnosed with TE using next-generation sequencing of pleural tissue. We analyzed the literature to improve clinicians' understanding of TE and how to properly diagnose and treat the disease. RESULTS: Laboratory results of the pleural effusion suggested a possible Mycobacterium tuberculosis infection, but pathogen-related tests were negative, and the diagnosis was eventually successfully confirmed by thoracoscopic pleural biopsy. CONCLUSIONS: The diagnosis of TE should be considered in young patients with pleural thickening of the empyema. Adenosine deaminase may provide diagnostic direction in patients with unexplained thorax abscess. Pleural biopsy, although an invasive procedure, is an essential diagnostic tool in some cases.

[Comparison of 1-year outcomes between Roux-en-Y gastric bypass and sleeve gastrectomy with Roux-en-Y duodenojejunal bypass in the patients of obesity with type 2 diabetes mellitus].

Objective: To compare the 1-year effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy with Roux-en-Y duodenal bypass (SG+RYDJB) on weight loss, remission of diabetes, and postoperative complications in patients with obesity and type 2 diabetes. Methods: A single-center retrospective cohort study was conducted at the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2020. Sixty-four patients with type 2 diabetes and body mass index (BMI) of 27.5-40.0 kg/m2 were included in this study and divided into the RYGB group (n=34) and the SG+RYDJB group (n=30). In both procedures, the biliopancreatic branch was measured 100 cm distal to the Treitz ligament, and the food branch was measured 100 cm distal to the gastric or duodenojejunal anastomosis. Patients were followed up by telephone or WeChat, a free messaging and calling app at 1, 3, 6, and 12 months postoperatively to determine their weight loss and remission of diabetes. The primary outcomes were the weight loss and reduction in blood glucose concentrations at 1 year after surgery and postoperative complications. Other postoperative changes, including body weight, BMI, percentage of total weight loss (%TWL), percentage of excess weight loss (%EWL), glycated hemoglobin A1c (HbA1c), and fasting blood glucose at 1 year after surgery were also assessed. Results: There were no significant differences in baseline data between the two groups (all P>0.05). No conversion to open surgery or death occurred in either group. Operation time was longer in the SG+RYDJB than the RYGB group (137.8±22.1 minutes vs. 80.0±24.9 minutes, t=9.779, P<0.001) and the incidence of perioperative complications was higher in the SG+RYDJB than the RYGB group (20% [6/30] vs. 2.9% [1/34], χ2=4.761, P=0.029). However, the postoperative hospital stay was similar between the two groups [3.0 (3.0, 4.3) days vs. 3.0 (4.0, 6.0) days, U=641.500, P=0.071]. Perioperative complications comprised small gastric pouch anastomotic leakage in one patient in the RYGB group and leakage (three patients) and bleeding (two patients with gastrointestinal bleeding and one with trocar site bleeding) in the SG+RYDJB group. Long-term complications were as follows. The incidence of anemia was significantly higher in the RYGB than the SG+RYDJB group (26.5% [9/34] vs. 3.3% [1/30], χ2=6.472, P=0.011). However, there were no significant differences in incidences of postoperative reflux, dumping syndrome, alopecia, diarrhea, constipation or foul-smelling flatus between the two groups (all P>0.05). Compared with 1 year before surgery, the body weights and fasting plasma glucose concentrations of patients in the SG+RYDJB and RYGB group (72.4±10.6 kg vs. 98.5±14.2 kg, respectively; 68.2±10.0 kg vs. 91.9±14.8 kg, respectively), BMI (25.2±2.9 kg/m2 vs. 34.3±4.2 kg/m2, respectively; 24.3±2.4 kg/m2 vs. 32.7±3.7 kg/m2, respectively) (5.5±1.6 vs. 10.6±3.3, respectively; 5.8±2.1 vs. 9.0±3.4, respectively); HbA1c (5.7±0.8 vs. 9.7±1.2, respectively; 9.1±1.9 vs. 5.9±0.9, respectively) were significantly lower at 1 year after surgery (all P<0.05). However, the % TWL (26.5%±6.0% vs. 25.6%±4.4%, t=0.663, P=0.510) and % EWL (109.1%±38.2% vs. 109.4%±40.3%, t=-0.026, P=0.026), rate of complete remission of diabetes at 1 year (80.0% [24/30] vs. 82.4% [28/34], χ2=0.058, P=0.810] did not differ significantly between the two groups (all P>0.05). Conclusions: Although SG+RYDJB surgery compared with RYGB is more difficult to perform, it can achieve similar weight loss and remission of diabetes and is associated with a lower incidence of anemia because of the preservation of the pylorus.

[Evaluation of the predictive effect of PD-L1 expression on survival in early triple-negative breast cancer].

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.

Allisartan Isoproxil Promotes Uric Acid Excretion by Interacting with Intestinal Urate Transporters in Hyperuricemic Zebrafish (Danio rerio).

To evaluate the urate-lowering effect and potential drug targets of antihypertensive agent allisartan isoproxil (ALI) and its bioactive metabolite EXP3174, we developed an acute hyperuricemic zebrafish model using potassium oxonate and xanthine sodium salt. Losartan potassium served as the positive control (reference drug). In this model, ALI and losartan potassium exerted a greater urate-lowering effect than EXP3174 indicating that the latter is not the critical substance for elimination of uric acid. The quantitative real-time PCR showed that ALI upregulates the expression of intestinal urate transporters genes ABCG2, PDZK1, and SLC2A9 (p<0.01). Thus, we can suggest that this substance promotes uric acid excretion mainly by interacting with intestinal urate transporters.

Acute Eosinophilic Pneumonia Masquerading as a Lung Abscess.

BACKGROUND: Acute Eosinophilic Pneumonia (AEP) is a rare form of non-infectious pneumonia that is easily missed and misdiagnosed because of its atypical clinical symptoms and misleading laboratory and imaging studies. METHODS: By reporting a case of an initial diagnosis of lung abscess, which was treated with antibiotics and then CT suggesting that the lesion continued to worsen, it was eventually confirmed to be AEP by lung biopsy, A joint literature analysis was conducted to improve clinicians' understanding of the diagnosis and treatment of AEP. RESULTS: Initially, because of the atypical ancillary findings, we thought the disease was a lung abscess, which was eventually confirmed by pathology as AEP. CONCLUSIONS: The presence of AEP needs to be considered when various laboratory findings point to infectious dis-ease, but anti-infection is not effective. Diagnosis can be confirmed by bronchoalveolar lavage and lung tissue biopsy. Prompt treatment can provide rapid relief and reduce the risk of patient death.

[Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation].

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) µg/L vs 74.35 (33.50-139.50) µg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

Deficient chaperone-mediated autophagy in macrophage aggravates inflammation of nonalcoholic steatohepatitis by targeting Nup85.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.

[Reinforced radiculoplasty for the treatment of symptomatic sacral Tarlov cysts: A clinical analysis of 71 cases].

OBJECTIVE: To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs). METHODS: A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery. RESULTS: In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred. CONCLUSION: For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.

Sex difference in the expression of PD-1 of non-small cell lung cancer.

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors.

[Surgical treatment of large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading].

OBJECTIVE: To investigate the surgical strategy for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. METHODS: The clinical data of 16 patients with large and giant recurrent meningioma in the middle and posterior third part of the superior sagittal sinus with extracranial invasion who underwent surgery in the Department of Neurosurgery of Peking University Third Hospital from May 2019 to May 2022 were retrospectively analyzed. All the patients underwent brain-enhanced magnetic resonance imaging (MRI), magnetic resonance venography (MRV), computed tomography angiography (CTA) and three-dimensional skull computed tomography (CT) before, to evaluate the extent of tumor invasion, the edema of brain tissue, the degree of skull damage, the blood supply of the tumor, and the degree of compression of the superior sagittal sinus, etc, and to formulate an individualized surgical plan. The neurological function of the patients was evaluated 1 week, 1 month, and 3 months after the operation, and the tumor condition was evaluated by brain-enhanced MRI 3 months, 6 months, and 1 year after the operation. RESULTS: The tumors in the 16 patients were all located in the middle and posterior 1/3 part of the superior sagittal sinus and invaded extracranially. Among them, 8 cases were operated for the second time, 6 cases for the third time, and 2 cases for the fourth time; In the last operation, the bone flap was used to repair the skull in 4 cases, and the titanium mesh was used in 12 cases; Tumor arterials of 3 cases were embolized under digital subtraction angiography (DSA). Tumors of 10 cases were resected at Simpson grade Ⅰ, and 6 cases at Simpson grade Ⅱ; 2 cases underwent decompressive craniectomy during operation, and 14 cases underwent cranioplasty at the same time; scalp incisions of 14 cases were directly sutured, and flap transposition was used in 14 cases. When evaluating nerve function after operation, the limb muscle strength was improved compared with that before operation, and the Karnofsky performance scale (KPS) score reached 100 points 3 months after operation. During the follow-up, 1 patient's tumor recurred after 1 year and received Gamma Knife treatment, and the rest of the patients had no recurrence during the follow-up period. CONCLUSION: Surgical treatment is the first choice for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. It is a safe and effective surgical method to take individualized surgical plan after detailed preoperative assessment of cerebral edema, tumor blood supply, venous sinus compression, and scalp invasion.

[Otologic disorders and management strategies in Turner syndrome].

Objective: To analyze the incidence and risk factors of otologic disorders in patients with Turner syndrome (TS), so as to provide management strategies for ear health. Methods: This study is a prospective study based on questionnaires and a cross-sectional study. The TS patients who visited our hospital from 2010 January to 2021 March were included (A total of 71 patients with TS were included in this study. the age of TS diagnosed was 3- to 11-year-old, age of visiting ENT department was 4- to 27-year-old) and the incidence of otologic diseases in different age groups was investigated by questionnaires. The cross-sectional study included ear morphology and auditory function assessment, and further analysis of the risk factors that related to ear disease. Prism was used for data analysis. Results: The investigation found that the incidence of acute otitis media in patients aged 3-6 and 7-12 years was higher than that of patients over 12 years old, which was 33.8%(24/71), 42.9%(30/70)and 23.5%(8/34), respectively; 21.1% (15/71) of patients were recurrent acute otitis media in patients aged 3-6 years, and about 46.6% (7/15)of them persisted beyond 6-year. The prevalence of otitis media with effusion in the three groups was 32.4%(23/71), 34.3%(24/70)and 38.2%(13/34), respectively; the recurrence rate of tympanocentesis was 100%(7/7), 42.9%(3/7)and 50.0%(1/2), which was significantly higher than that of grommet insertion. For age groups of 3-6 and 7-12 years, the prevalence of acute otitis media and secretory otitis media was lower in the X chromosome structure abnormal patients; while for patients older than 12 years, otitis media with effusion was the highest prevalence in Y-chromosome-containing karyotypes. In addition, the prevalence of acute otitis media and otitis media with effusion in patients with other system diseases were increased significantly. A cross-sectional study found that 7.0% (5/71)of the lower auricular, 4.2% (3/71)of the external auditory canal narrow, and 38.0% (27/71)of the tympanic membrane abnormality. 35.2%(25/71) had abnormal hearing, including 17 cases of conductive deafness, 6 cases of sensorineural hearing loss, and 2 cases of mixed deafness. The rest of the patients had normal hearing, but 6 of them had abnormalities in otoacoustic emission. Eustachian tube function assessment found that the eustachian tube dysfunction accounted for 38%(27/71). Hearing loss and abnormal Eustachian tube function were not significantly related to karyotype(Chi-square 2.83 and 2.84,P value 0.418 and 0.417), but significantly related to other system diseases(Chi-square 13.43 and 7.53,P value<0.001). Conclusions: The incidence of TS-related otitis media and auditory dysfunction is significantly higher than that of the general population. It not only occurs in preschool girls, but also persists or develops after school age. Accompanied by other system diseases are risk factors for ear diseases. Clinicians should raise their awareness of TS-related ear diseases and incorporate ear health monitoring into routine diagnosis and treatment.

Mechanism of ALDH2 improves the neuronal damage caused by hypoxia/reoxygenation.

OBJECTIVE: To investigate the protective effect and mechanism of ALDH2 on PC12 cells and brain nerve tissue injury under hypoxia. MATERIALS AND METHODS: The hypoxia model of PC12 cells with low ALDH2 expression was established and screened. The eukaryotic expression vector of wild type pEGFP-N1-ALDH2 and blank plasmid pEGFP-N1 were constructed and transfected into PC12 hypoxia cells respectively. After reoxygenation culture, the morphology, quantity, ALDH2 expression level and apoptosis rate of the two groups were observed, and the role of ALDH2 in cell hypoxia injury was analyzed. Eighty SD rats were randomly divided into model group (ischemia-reperfusion injury group), Alda-1 group (intraperitoneal injection of alda-1 12 hours before and after modeling), DMSO group (intraperitoneal injection of dimethyl sulfoxide) and sham operation group, with 20 rats in each group. The neurobehavioral score, apoptosis rate of nerve cells, the content and activity of ALDH2 in active cerebral cortex and hippocampal CA1 area were compared. RESULTS: The number of PC12 cells in hypoxia group was lower than that in control group. The expression level of ALDH2 protein in PC12 cells after 4 hours of hypoxia was lower than that in normal culture group. The number of PC12 cells transfected with wild-type recombinant plasmid was significantly more than that of blank plasmid group. Compared with the hypoxia group, the pre apoptotic and post apoptotic cells in wild type transfection group decreased after hypoxia treatment. Compared with sham operation group, nerve injury and apoptosis were increased in group M and DMSO, while ALDH2 activity and expression did not change significantly. Compared with M group and DMSO group, the nerve injury and apoptosis in Alda-1 group were improved, ALDH2 activity was increased, and ALDH2 expression was not significantly changed in Alda-1 group. CONCLUSIONS: Increasing the expression of ALDH2 or enhancing the activity of ALDH2 can improve the injury of neurons induced by hypoxia/reoxygenation.

[Microscopic resection of lumbar intraspinal tumor through keyhole approach: A clinical study of 54 cases].

OBJECTIVE: To explore the feasibility and key technology of microscopic resection of lumbar intraspinal tumor through microchannel keyhole approach. METHODS: The clinical features, imaging characteristics and surgical methods of 54 cases of lumbar intraspinal tumor which were microscopically operated by microchannel from February 2017 to September 2019 were reviewed and analyzed. There were 8 cases of extradural tumor, 3 cases of extra-and intradural tumor and 43 cases of subdural extramedullary tumor (including 3 cases of ventral spinal tumor). The tumors were 0.5-3.0 cm in diameter. The clinical symptoms included 49 cases of pain in the corresponding innervation area, 5 cases of sensory disturbance (numbness) at or below the tumor segment, 7 cases of limb weakness and 2 cases of urination and defecation dysfunction. RESULTS: In the study, 37 tumors were resected through hemilaminectomy, 14 tumors were resected through interlaminar fenestration, 3 tumors were resected through hemilaminectomy or interlaminar fenestration combined with facetectomy of medial 1/4 facet. All of the 54 tumors were totally resected. The operation time was 75-135 min, with an average of 93.3 min. The postoperative hospital stay was 4-7 days, with an average of 5.7 days. Postoperative pathology included 34 cases of schwannoma, 4 cases of meningioma, 9 cases of ependymoma, 1 case of enterogenous cyst, 5 cases of teratoma/epidermoid/dermoid cyst, and 1 case of paraganglioma. No infection or cerebrospinal fluid leakage was found after operation. No neurological dysfunction occurred except 1 case of urination dysfunction and 4 cases of limb numbness. The follow-up period ranged from 3 to 33 months with an average of 14.4 months. Five patients with new onset symptoms returned to normal. The pain symptoms of 49 patients were completely relieved; 4 of 5 patients with hypoesthesia recovered completely, the other 1 patient had residual mild hypoesthesia; 7 patients with limb weakness, and 2 patients with urination and defecation dysfunction recovered to normal. No spinal instability or deformity was found, and no recurrence or residual tumors were found. According to McCormick classification, they were of all grade Ⅰ. CONCLUSION: The lumbar intraspinal extramedullary tumors within two segments (including the ventral spinal tumors) can be totally resected at stage Ⅰ through microchannel keyhole approach with appropriate selection of the cases. Microchannel technique is beneficial to preserve the normal structure and muscle attachment of lumbar spine, and to maintain the integrity and stability of lumbar spine.

Iodine Maps from Dual-Energy CT to Predict Extrathyroidal Extension and Recurrence in Papillary Thyroid Cancer Based on a Radiomics Approach.

BACKGROUND AND PURPOSE: Accurate prediction of extrathyroidal extension and subsequent recurrence is crucial in papillary thyroid cancer clinical management. Our aim was to conduct iodine map-based radiomics to predict extrathyroidal extension and to explore its prognostic value for recurrence-free survival in papillary thyroid cancer. MATERIALS AND METHODS: A total of 452 patients with papillary thyroid cancer were retrospectively recruited between June 2017 and June 2020. Radiomics features were extracted from noncontrast images, dual-phase mixed images, and iodine maps, respectively. Random forest and least absolute shrinkage and selection operator (LASSO) were applied to build 6 radiomics scores (noncontrast radiomics score_random forest; noncontrast rad-score_LASSO; mixed rad-score_random forest; mixed rad-score_LASSO; iodine radiomics score_random forest; iodine radiomics score_LASSO) respectively. Logistic regression was used to construct 6 radiomics models incorporating 6 radiomics scores with clinical risk factors and to compare them with the clinical model. A radiomics model that achieved the highest performance was presented as a nomogram and assessed by discrimination, calibration, clinical usefulness, and prognosis evaluation. RESULTS: Iodine radiomics scores performed significantly better than mixed radiomics scores. Both of them outperformed noncontrast radiomics scores. Iodine map-based radiomics models significantly surpassed the clinical model. A radiomics nomogram incorporating size, capsule contact, and iodine radiomics score_random forest was built with the highest performance (training set, area under the curve = 0.78; validation set, area under the curve = 0.84). Stratified analysis confirmed the nomogram stability, especially in group negative for CT-reported extrathyroidal extension (area under the curve = 0.69). Nomogram-predicted extrathyroidal extension risk was an independent predictor of recurrence-free survival. A high risk for extrathyroidal extension portended significantly lower recurrence-free survival than low risk (P < .001). CONCLUSIONS: Iodine map-based radiomics might be a supporting tool for predicting extrathyroidal extension and subsequent recurrence risk in patients with papillary thyroid cancer, thus facilitating clinical decision-making.