Objective:To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis.Methods:Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi′an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed.Results:The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma.Conclusions:Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.

ObjectiveTo systematically review the effects of mind-body exercise on sleep quality, and to sort out the influencing factors of mind-body exercise intervention program. MethodsLiteratures about the effects of mind-body exercise on sleep were searched in PubMed, Web of Science, Science Direct, Cochrane Library, CNKI, VIP and Wanfang data from establishment to June 1, 2022. The author, country, publication time, study object, study method, intervention process, measurement tool and outcome index were extracted from the selected literature. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate the methodological quality. ResultsA total of 14 English literatures were included, all of which were randomized controlled trails, and the overall research quality was good. Mind-body exercise methods included Taijiquan, Qigong and Baduanjin. Most of the subjects were old and sick people. Physical exercise intervention with a duration of ten to twelve weeks, a single time of 60 minutes and at least two to three times a week could improve sleep quality to the greatest extent. The health status of the participants was an important factor affecting the effect of the intervention. ConclusionMind-body exercise can improve sleep quality, relieve anxiety and depression, and promote mental health.

AIM: With building a proliferation model of PA-induced VSMC, the effect of ATGL, a key fat metabolism enzyme, on the phenotype transformation of VSMC was preliminarily explored. METHODS: 40 μmol/L Atglistatin was added to the proliferation model of VSMC induced by PA (50 μmol/L, 100 μmol/L, and 200 μmol/L, respectively) at separately administered concentrations, and cell viability and cell proliferation were detected by CCK-8 and EDU; cell migration ability was detected by scratch assay; oil red staining was used to detect the accumulation of lipid droplets in VSMC was detected by oil red staining; the effects of PA on ATGL as well as the effects of smooth muscle contraction phenotype proteins were examined by Western blot. RESULTS: PA at a concentration of 100 μmol/L could significantly induce VSMC proliferation, promote lipophagy and increase lipid droplet accumulation in VSMC; meanwhile, Atglistatin could exacerbate these changes caused by PA and increase lipid droplet accumulation in VSMC. CONCLUSION: Atglistatin exacerbates PA-induced VSMC proliferation and increases VSMC lipid droplet accumulation, and exacerbates transformation of proliferative phenotype of VSMC.

Objective To observe the clinical efficacy and safety of nifedipine controlled-release tablets on the antihypertensive effect of hypertensive patients under high altitude environment. Methods 42 hypertensive inpatients in the 940th hospital (altitude 1500 ) were set to the plain hypertension group, and 42 cases of hypertensive inpatients in Bayi hospital (altitude 3800 m) were set to the plateau hypertension group. Both groups of patients were given nifedipine controlled-release tablets 30 mg daily, taken orally in the morning for 6 consecutive days. Monitor blood pressure and heart rate three times a day to compare the clinical efficacy and occurrence of adverse drug reactions in the two groups. Results After treatment, the total effective rates of the high-altitude hypertension group and the plain hypertension group were 47.62% (20 cases/42 cases) and 76.19% (32 cases/42 cases) respectively with no statistical difference (P<0.05). The adverse drug reactions of the two groups of patients were tachycardia and palpitations. The incidence of total adverse drug reactions in the high-altitude hypertension group and the plain hypertension group were 14.29% and 11.90% respectively with no statistical difference (P>0.05). Conclusion The high-altitude hypoxic environment could affect the antihypertensive effect of nifedipine controlled-release tablets, which could not control the patient's blood pressure effectively in the short term.

Plateau environment will affect the metabolism of drugs in the body, which will cause changes in pharmacokinetic parameters, expression and function of drug metabolizing enzymes and transporters. With the rapid development of the pharmaceutical industry, therapeutic drug monitoring (TDM) has been widely paid attention to as a basis for personalized drugs. What impact does the plateau environment on monitoring drugs? In this literature review, we will summarize the types of commonly used therapeutic monitoring drugs, therapeutic windows, and blood samples, analyze the effects of plateau hypoxic environment on the metabolism of commonly used monitoring drugs, provide a reference for the clinical treatment and monitoring drugs of plateau, better ensure the rational use of drugs in the plateau population, and also provide a reference for the later research group to conduct the monitoring of plateau therapeutic drugs and the selection of research drugs.

A 77-year-old female patient underwent a laparoscopic left radical nephrectomy for renal malignant neoplasm.She received an IV infusion of cefoperazone sodium and tazobactam sodium 2 g about 30 minutes before surgery and an IV infusion of hydrocortisone injection 400 mg during the operation.On the 2nd day after surgery,intravenous infusion of cefoperazone sodium and tazobactam sodium (2 g twice daily) and hydrocortisone injection (200 mg once daily) were given sequentially.On the 3rd day after operation,about 30 min after completion of the IV infusion of hydrocortisone injection,the patient's blood pressure dropped suddenly to 84/48 mmHg,her heart rate was 150 beats per minute,and clouding of consciousness,lethargy,generalized flush and sweating appeared.Adrenal crisis was considered.Dexamethasone,hydrocortisone,dopamine,epinephrine,and etc.were successively given to rescue her.About 30 minutes later,the patient's symptoms improved slightly and then the patient was immediately transferred to ICU.In ICU,cefoperazone sodium and tazobactam sodium was continued according to the original scheme,hydrocortisone injection was changed to 150 mg twice daily,and the 2 groups of drugs were infused at 2-hour intervals.At the same time,dopamine 360 mg dissolved in 50 ml of 0.9％ sodium chloride injection was administered intravenously via an infusion pump.The patient's condition improved.On the 7th day after operation,the 2 groups of drugs were intravenously infused sequentially again and the similar symptoms appeared again.The pharmacist considered that the disulfiram-like reactions was caused by the combined use of cefoperazone sodium and tazobactam sodium and hydrocortisone injection and suggested that the two drugs should be discontinued.After the drugs withdrawal,no similar symptoms recurred.

A 77-year-old female patient underwent a laparoscopic left radical nephrectomy for renal malignant neoplasm.She received an IV infusion of cefoperazone sodium and tazobactam sodium 2 g about 30 minutes before surgery and an IV infusion of hydrocortisone injection 400 mg during the operation.On the 2nd day after surgery,intravenous infusion of cefoperazone sodium and tazobactam sodium (2 g twice daily) and hydrocortisone injection (200 mg once daily) were given sequentially.On the 3rd day after operation,about 30 min after completion of the IV infusion of hydrocortisone injection,the patient's blood pressure dropped suddenly to 84/48 mmHg,her heart rate was 150 beats per minute,and clouding of consciousness,lethargy,generalized flush and sweating appeared.Adrenal crisis was considered.Dexamethasone,hydrocortisone,dopamine,epinephrine,and etc.were successively given to rescue her.About 30 minutes later,the patient's symptoms improved slightly and then the patient was immediately transferred to ICU.In ICU,cefoperazone sodium and tazobactam sodium was continued according to the original scheme,hydrocortisone injection was changed to 150 mg twice daily,and the 2 groups of drugs were infused at 2-hour intervals.At the same time,dopamine 360 mg dissolved in 50 ml of 0.9％ sodium chloride injection was administered intravenously via an infusion pump.The patient's condition improved.On the 7th day after operation,the 2 groups of drugs were intravenously infused sequentially again and the similar symptoms appeared again.The pharmacist considered that the disulfiram-like reactions was caused by the combined use of cefoperazone sodium and tazobactam sodium and hydrocortisone injection and suggested that the two drugs should be discontinued.After the drugs withdrawal,no similar symptoms recurred.