Objective To investigate the correlation between spread through air space (STAS) of sub-centimeter non-small cell lung cancer and clinical characteristics and radiological features, constructing a nomogram risk prediction model for STAS to provide a reference for the preoperative planning of sub-centimeter non-small cell lung cancer patients. Methods The data of patients with sub-centimeter non-small cell lung cancer who underwent surgical treatment in Nanjing Drum Tower Hospital from January 2022 to October 2023 were retrospectively collected. According to the pathological diagnosis of whether the tumor was accompanied with STAS, they were divided into a STAS positive group and a STAS negative group. The clinical and radiological data of the two groups were collected for univariate logistic regression analysis, and the variables with statistical differences were included in the multivariate analysis. Finally, independent risk factors for STAS were screened out and a nomogram model was constructed. The sensitivity and specificity were calculated based on the Youden index, and area under the curve (AUC), calibration plots and decision curve analysis (DCA) were used to evaluate the performance of the model. Results A total of 112 patients were collected, which included 17 patients in the STAS positive group, consisting of 11 males and 6 females, with a mean age of (59.0±10.3) years. The STAS negative group included 95 patients, with 30 males and 65 females, and a mean age of (56.8±10.3) years. Univariate logistic regression analysis showed that male, anti-GAGE7 antibody positive, mean CT value and spiculation were associated with the occurrence of STAS (P＜0.05). Multivariate regression analysis showed that associations between STAS and male (OR=5.974, 95%CI 1.495 to 23.872), anti-GAGE7 antibody positive (OR=11.760, 95%CI 1.619 to 85.408) and mean CT value (OR=1.008, 95%CI 1.004 to 1.013) were still significant (P＜0.05), while the association between STAS and spiculation was not significant anymore (P=0.438). Based on the above three independent predictors, a nomogram model of STAS in sub-centimeter non-small cell lung cancer was constructed. The AUC value of the model was 0.890, the sensitivity was 76.5%, and the specificity was 91.6%. The calibration curve was well fitted, suggesting that the model had a good prediction efficiency for STAS. The DCA plot showed that the model had a good clinically utility. Conclusion Male, anti-GAGE7 antibody positive and mean CT value are independent predictors of STAS positivity of sub-centimeter non-small cell lung cancer, and the nomogram model established in this study has a good predictive value and provides reference for preoperative planning of patients.

BACKGROUND:Studies have shown that there is a close association between spinal cord injury and ferroptosis,and that tetramethylpyrazine has the function of regulating redox reactions. OBJECTIVE:To investigate the regulatory effect of tetramethylpyrazine on ferroptosis in rats with spinal cord injury and its mechanism. METHODS:Thirty-six female specific pathogen-free Sprague-Dawley rats were randomly divided into sham-operated group,model group and tetramethylpyrazine group,with 12 rats in each group.Animal models of spinal cord injury were established using the modified Allen's method in the latter two groups.No treatment was given in the sham-operated group,while rats in the model and tetramethylpyrazine groups were given intraperitoneal injection of normal saline and tetramethylpyrazine solution,once a day,for 28 days. RESULTS AND CONCLUSION:The Basso,Beattie&Bresnahan Locomotor Rating Scale score in the tetramethylpyrazine group was lower than that in the sham-operated group but higher than that in the model group after 14,21,and 28 days of treatment(P＜0.05).After 28 days of treatment,hematoxylin-eosin staining showed that in the model group,the spinal cord tissue of rats showed cavity formation,necrotic tissue and inflammatory infiltration with fibrous tissue formation;in the tetramethylpyrazine group,the area of spinal cord tissue defects was smaller,and inflammatory infiltration and fibrous tissue formation were less than those in the model group.After 28 days of treatment,Prussian blue staining showed that a large amount of iron deposition was seen in the spinal cord tissue of rats in the model group,and less iron deposition was seen in the spinal cord tissue of rats in the tetramethylpyrazine group than in the model group.After 28 days of treatment,the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were decreased(P＜0.05)and the level of malondialdehyde was increased in the model group compared with the sham-operated group(P＜0.05);the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were increased(P＜0.05)and the level of malondialdehyde was decreased in the tetramethylpyrazine group compared with the model group(P＜0.05).After 28 days of treatment,qRT-PCR and western blot assay showed that the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the model group were decreased compared with those in the sham-operated group(P＜0.05),while the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the tetramethylpyrazine group were increased compared with those in the model group(P＜0.05).Immunofluorescence staining showed that after 28 days of treatment,the neuronal nuclei positive staining in the spinal cord of rats was the most in the sham-operated group and the least in the model group.To conclude,tetramethylpyrazine can improve motor function and play a neuroprotective role in rats with spinal cord injury by regulating ferroptosis.

Topical semi-solid preparations include creams,ointments,gels and other dosage forms,which contain various excipients such as emulsifiers,preservatives,thickeners or emollient agents,etc.They can be single-phase system,or multiple system consisting of continuous phase and disperse phase thanks to its complex design of formulation and manufacturing process.Rheology properties are critical quality attributes of topical semi-solid preparations,which can comprehensively reflect the difference in microstructure such as the substance distribution and aggregation state of the product,and is related to other attributes such as in vitro release,in vitro penetration,stability and cutaneous sense.It is one of the most effective means to evaluate the quality equivalence between generic drugs and innovator drugs.After reviewing domestic,foreign literature and relative policies,this paper described the research status and test methods of rheology,analyzed the possible factors affecting rheological properties,discussed the quality differences reflected in rheological data,in order to guide pharmaceutical manufacturers to improve their formulations and processes and provide help for the development and quality equivalence research of such preparations.

Objective:To prospectively observe the changes of tumor-related symptoms in patients with nasopharyngeal carcinoma following the administration of nimotuzumab one week before radiotherapy.Methods:Non-metastatic nasopharyngeal carcinoma patients with positive epidermal growth factor receptor (EGFR) expression and symptoms caused by the primary lesion or metastatic cervical lymph nodes admitted to Cancer Hospital of Chinese Academy of Medical Sciences were prospectively recruited. Investigators recorded tumor-related symptoms in recruited patients one day before the first administration of nimotuzumab (D0) and conducted follow-up visits from day 2 to day 7 after the first administration (D2-D7) to document symptom changes. All recruited patients were asked to assess tumor-related symptoms on D0 and D7 by visual analogue scale (VAS) scores. VAS scores were analyzed by paired t-test. Results:From June 2020 to April 2023, a total of 21 patients met the inclusion criteria. The median age was 49 years (range: 27-69 years), with a male-to-female ratio of 1.3:1. Among the patients, 17 patients (81%) received concurrent nimotuzumab for 8 cycles, 7 cycles for 3 cases (14%), and 6 cycles for 1 case (5%), respectively. All patients completed symptom assessments as required. The overall response rate of symptoms after the first administration of nimotuzumab was 62%, with response rates of 4/6、5/8、4/10、4/10、4/11、3/11 for tinnitus, headache, aural fullness, secondary pain caused by neck mass, nasal bleeding, and nasal obstruction, respectively. The VAS scores for overall symptoms were significantly decreased after the administration of nimotuzumab one week before radiotherapy ( P<0.001), with the most significant decrease in VAS scores for tinnitus, aural fullness, and headache. Conclusion:The administration of nimotuzumab one week before radiotherapy significantly alleviates tumor-related symptoms in patients with nasopharyngeal carcinoma, particularly in alleviating tinnitus, aural fullness, and headache.

Objective:To investigate the laboratory detection methods for immune hemolytic transfusion reactions caused by anti-tigecycline antibody and the clinical diagnosis and treatment of one patient.Methods:The correlation between hemolysis-related laboratory indexes of the patient and the duration of medication was analyzed. Blood samples of the patient were tested using direct anti-human globulin test, free antibody test, and release test. Erythrocyte sensitization method and immune complexome analysis were used to detect the antibody against tigecycline in the serum of the patient. The properties and the titers of anti-tigecycline antibody were analyzed.Results:Anti-tigecycline antibody was found in the patient through the erythrocyte sensitization method and the immune complexome analysis, and the result of the direct anti-human globulin test was positive. The clinical symptoms and physical signs of the patient improved rapidly after withdrawal of tigecycline and blood transfusion. The patient was discharged after 14-day treatment with immunoglobulin and hormone.Conclusions:Tigecycline can cause hemolytic transfusion reactions. Serological tests are essential for the diagnosis of drug-induced hemolytic anemia. Withdrawal of medications and symptomatic treatment should be conduceted immediately when patients develop drug-related hemolytic anemia.

Objective:This study aimed to evaluate the clinical features and treatment outcomes of the value of response-adapted treatment following radiotherapy and induction chemotherapy follwing subsequent comprehensive therapy in patients with resectable locally advanced hypopharyngeal carcinoma. Methods:This cohort study was conducted from September 2010 to September 2020 in our hospital, 231 patients pathologically confirmed stage Ⅲ and ⅣB resectable locally advanced hypopharyngeal carcinoma included. For the IC-directed ART strategy, IC is used to select good candidates to receive radical RT or CCRT, and others undergo surgery. He response-adapted strategy was determined based on the primary tumor response, which was evaluated at a dose of 50 Gy. If the response reached complete response or partial response（more than 80% tumor regression）, patients received radical RT or CCRT; otherwise, they received surgery, if possible, at 4 to 6 weeks after RT. The end points of the study were OS（overall survival）, progression free survival（PFS）, locoregional recurrence-free survival（LRRFS） and LDFS. Results:In IC-directed group, 75.0%（57/76） patients reached PR after 2 cycles of induction chemotherapy. While in RT-directed group, 70.3%（109/155） patients reached large PR at dose of 50 Gy. The median interquartile range follow-up period of the whole cohort was 63.8 months. The 5-year OS, PFS, LRRFS and SFL of the whole cohort were 47.9%、39.6%、44.3% and 36.2%, respectively. In evaluations based on the different treatment strategies, the 5-year OS and SFL were 51.3% versus 37.0%（HR 0.67; 95%CI 0.43-1.05; P=0.07） and 27.8% versus 39.8%（HR 0.68; 95%CI 0.46-0.99; P=0.04） between IC-directed and RT-directed groups. In additional, surgery complications did not significantly differ between these two groups. Conclusion:In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, and higher laryngeal preservation compared with IC-directed strategies. This approach could provide a feasible laryngeal preservation strategy in patients with resectable locally advanced hypopharyngeal carcinoma.
Male ; Humans ; Cohort Studies ; Chemoradiotherapy ; Carcinoma ; Hypopharyngeal Neoplasms/therapy* ; Induction Chemotherapy

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.
Humans ; Carcinoma/diagnosis* ; Oropharyngeal Neoplasms/diagnosis* ; Retrospective Studies ; Neoplasms, Second Primary/diagnosis*

Objective:To evaluate the efficacy and safety of nimotuzumab in the treatment of advanced head and neck tumors by using meta-analysis.Methods:Randomized controlled trials (RCT) of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) treated with nimotuzumab were searched from databases (Cochrane Library, PubMed, Embase, Wanfang Data and CNKI) for meta-analysis. The efficacy evaluation indexes included overall survival, progression-free survival, disease-free survival, objective response rate, and complete response rate. Adverse reactions were analyzed for safety evaluation. The heterogeneity results were evaluated by Chi-square test, the degree of heterogeneity was evaluated by I2, and the literature was statistically analyzed by random effects model. Results:A total of 11 RCT were included, consisting of 1 202 patients (602 in the intervention group and 600 in the control group). Compared with the control group, the overall survival was significantly prolonged, death risk was decreased by 22% ( HR=0.78, 95% CI=0.63-0.95, P=0.014), the progression-free survival was prolonged and the risk of disease progression was declined by 35% ( HR=0.65, 95% CI=0.53-0.81, P<0.01), and the disease-free survival was prolonged and the risk of recurrence was decreased by 29% ( HR=0.71, 95% CI=0.55-0.91, P<0.01), the objective response rate ( RR=1.37, 95% CI=1.20-1.55, P<0.01) and complete response rate ( RR=1.30, 95% CI=1.15-1.46, P<0.01) were significantly improved in the intervention group. In addition, adding nimotuzumab did not increase the incidence of adverse reaction ( RR=0.98, 95% CI=0.93-1.03, P=0.41). Conclusion:Nimotuzumab can significantly prolong long-term survival and improve short-term efficacy with high safety in LA-HNSCC patients.

Objective:To evaluate the incidence, clinical characteristics and prognosis of second primary malignancies (SPMs) among patients with hypopharyngeal carcinoma (HPC) in real-world analysis.Methods:A total of 594 HPC patients admitted to Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2010 to 2018 were retrospectively analyzed.The incidence and clinical characteristics of HPC patients complicated with SPMs were analyzed. Clinical efficacy was compared among different groups.Results:With a median follow-up time of 66.9 months, SPMs were present in 36.4% (216/594) of HPC patients: 22.2% (132/594) were synchronous and 14.1% (84/594) were metachronous. The upper aerodigestive tract was the most common involved region. Compared with patients without SPMs, patients with synchronous and metachronous carcinoma in situ had similar 5-year overall survival (OS) of 42.2% vs. 44.5% ( P=0.958) and 62.2% vs. 44.5% ( P=0.240), respectively. Patients with synchronous invasive SPMs had a worse 5-year OS of 27.2% vs. 44.5% in their counterparts without SPMs ( P=0.001). Patients with metachronous invasive SPMs had similar 5-year OS of 50.2% vs. 44.5% in their counterparts without SPMs ( P=0.587). SPMs accounted for 42.5% of total death in metachronous invasive SPMs group. Conclusions:Patients with HPC have a high probability of developing SPMs. Moreover, the incidence of complicated with esophageal/gastric carcinoma in situ or metachronous SPMs exerts no effect on prognosis, while the occurrence of synchronous SPMs significantly affectes the prognosis of patients. However, the incidence of SPMs is still one of the main death causes in metachronous invasive SPMs group.