Objective To investigate the efficacy and safety of intravenous thrombolysis with low-dose and standard-dose recombinant tissue plasminogen activator(rt-PA)in the elderly patients(aged over 80 years)with acute ischemic stroke(AIS).Methods A total of 201 elderly patients with AIS treated at Tianjin Fourth Central Hospital from February 2019 to February 2023 were prospectively included and randomly assigned to the rt-PA low-dose group(n=93,0.6 mg/kg)and rt-PA standard-dose group(n=108,0.9 mg/kg).The incidence of intra-cranial hemorrhage,symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,neurologic deterioration within 7 days and mortality within 90 days were observed to evaluate the safety.The neurologic improvement rate and good prognosis rate at 90 days were used to evaluate the effectiveness.A stratified analysis of 90-day outcomes was performed based on stroke severity and age.Results The incidence of intracranial hemorrhage,symptomatic intracranial hemorrhage and fatal intracranial hemorrhage within 7 days in rt-PA low-dose group was lower than that in rt-PA standard-dose group(P＜0.05).There were no statistically significant differences between the two groups concerning the residual safety index and the effectiveness index.The 90-day good prognosis rate of moderate stroke sub-group and of≥90 years of age sub-group in rt-PA low-dose group were both higher than that of rt-PA standard-dose group(P＜0.05).Conclusions For AIS patients with moderate stroke and aged over 90 years,intravenous thrombolytic therapy with rt-PA 0.6 mg/kg is recommended.

With the progress of comprehensive treatment of breast cancer, the surgical treatment of axillary lymph nodes presents a degraded treatment mode under the guidance of evidence-based medicine. The indications and contraindications of sentinel lymph node biopsy for early breast cancer have been very clear, but there are still many specific problems in clinical practice that surgeons are concerned about. This article discusses the recently published research on sentinel lymph node biopsy in order to draw the attention of surgical colleagues to the new hot issues of sentinel lymph node biopsy in early breast cancer, and promote standardized surgery and the promotion of new treatment concepts.

Acute ischemic stroke (AIS) is a kind of central nervous system disease that seriously threatens human health and life. Current treatment for AIS is mainly reperfusion. However, the time-sensitive of reperfusion limits its clinical application, and a considerable part of patients within the time window cannot achieve the expected effect after reperfusion; related complications of reperfusion have not been completely solved. So far, some clinical trials have confirmed that neuroprotectants are useful supplements and adjuncts to reperfusion. This paper reviews the recent advance in neuroprotectants combined with reperfusion in AIS to provide references for AIS treatment.

Objective To explore the correlation between lumbar spine bone mineral density and the occurrence of large rotator cuff tears. Methods A total of 109 patients with arthroscopic shoulder surgery in the Department of Arthroplasty Surgery in Kunshan Hospital of Traditional Chinese Medicine from January 2018 to October 2023 were selected and divided into large rotator cuff tear group (n=27) and small rotator cuff tear group (n=82) according to the severity of the rotator cuff tears. General materials of patients were collected, and multivariate Logistic regression analysis was used to investigate the correlation between lumbar spine bone mineral density and the occurrence of large rotator cuff tears. Results The large rotator cuff tear group had significant higher age and higher proportion of patients with a history of trauma compared to the small rotator cuff tear group (P < 0.05); additionally, the levels of total cholesterol, albumin, serum magnesium, total hip bone mineral density, and lumbar spine bone mineral density were significantly lower in the large rotator cuff tear group (P < 0.05). The results of multivariate Logistic regression analysis indicated that lumbar spine bone mineral density was associated with the occurrence of large rotator cuff tears. The prevalence of large rotator cuff tears across the four quartile intervals of lumbar spine bone mineral density named as Q1 (< 0.870 g/cm²), Q2 (0.870~ < 0.991 g/cm²), Q3 (0.991~1.137 g/cm²), and Q4 (>1.137 g/cm²) were 48.15%, 29.63%, 18.52% and 3.70% respectively, showing a gradual decreasing trend with significant differences (P < 0.05). Conclusion There is a correlation between lumbar spine bone mineral density and large rotator cuff tears. The lower the bone density of the lumbar spine is, the higher the risk of large rotator cuff tears will be.

Objective To analyze the application value of a Nomogram model established on clinical and ultrasound features of thyroid in modifying classification results of the Chinese Thyroid Imaging Reporting and Data System (C-TI-RADS) by ultrasound physicians. Methods The clinicopathological ultrasound materials of patients with surgical resection for thyroid nodules in Sichuan Provincial People's Hospital (training set, n=841) and Sichuan Mianyang 404 Hospital (external validation set, n=295) from January 2021 to December 2022 were retrospectively analyzed, and preoperative thyroid ultrasound was used to classify thyroid nodules by C-TI-RADS. Univariate and Multivariate Logistic regression analyses were used to screen independent predictors in the training set and a Nomogram model was constructed, and Bootstrap resampling was used for internal validation; ultrasound physicians in Sichuan Mianyang 404 Hospital were charged in external verification based on this Nomogram model. Receiver operating characteristic (ROC) curve and calibration curve were drawn to evaluate the efficacy of the model and its clinical value in modifying the classification results by C-TI-RADS. Results Univariate and Multivariate Logistic regression analyses showed that gender, age, maximum diameter of nodules, the number of nodules, ultrasound abnormalities of cervical lymph nodes and C-TI-RADS classification were the independent factors for predicting the modified classification results of C-TI-RADS by ultrasound physicians (P < 0.05). Consistency index of the Nomogram model constructed based on these factors was 0.842 (95%CI, 0.816 to 0.867), the area under the curve (AUC) was 0.842, sensitivity was 92.9%, specificity was 63.7%, and accuracy was 75.9%. The prediction results of the Nomogram model were in good agreement with the actual situation in both the training set and the external validation set. Conclusion Nomogram model based on clinical and ultrasound features of thyroid shows good predictive accuracy in modifying classification results of C-TI-RADS by ultrasound physicians, which has potential clinical application value.

Neoadjuvant therapy has been continuously improved the outcomes of early breast cancer patients, and more patients with positive axillary lymph node achieve complete pathological responds. The timing of sentinel lymph node biopsy for patients receiving neoadjuvant therapy has also had a new strategy, especially for the patients with clinical positive axillary lymph node before treatment and become clinical negative after neoadjuvant therapy, sentinel lymph node biopsy after neoadjuvant therapy has gradually become a standard axillary surgery procedure. However, there are still many differences in clinical practice domestic in China and abroad. This article discussed the timing of sentinel lymph node biopsy in patients with early breast cancer undergoing neoadjuvant therapy, in order to draw the attention of domestic surgical colleagues to this issue and promote standardized surgery and multidisciplinary cooperation.

Objective:To investigate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis combined with edaravone dexborneol at different timing in super elderly patients (aged≥85 years) with moderate to severe acute ischemic stroke (AIS).Methods:A prospective study was performed. Seventy-one super elderly patients with moderate to severe AIS treated with rt-PA intravenous thrombolysis combined with edaravone dexborneol from December 2020 to March 2023 in Department of Neurology, Affiliated Fourth Central Hospital of Nankai University were selected and randomly divided into early group ( n=35) and advanced group ( n=36); patients in the early group were given edaravone dexborneol immediately after rt-PA intravenous thrombolysis, and patients in the advanced group were given edaravone dexborneol 24 h after rt-PA intravenous thrombolysis. In addition, 31 patients with moderate to severe AIS received rt-PA intravenous thrombolysis only in Department of Neurology of the hospital from August 2018 to December 2020 were selected as control group. Differences in efficacy and safety indexes among the 3 groups were compared. Results:After 7 d of treatment, the improvement rate of neurological function in early group was significantly higher than that in control group and advanced group ( P<0.05). After 90 d of treatment, modified Rankin scale (mRS) scores in early group were statistically lower than those in control group and advanced group ( P<0.05); good prognosis rate in early group was statistically higher than that in control group and advanced group ( P<0.05). The incidences of intracranial hemorrhage and symptomatic intracranial hemorrhage in early group were significantly lower than those in control group and advanced group ( P<0.05). After 30 and 90 d of treatment, the advanced group had significantly lower mortality than the control group, but significantly higher mortality than the early group ( P<0.05). Conclusion:Edaravone dexborneol immediately after rt-PA intravenous thrombolysis is the optimal timing for super elderly patients with moderate to severe AIS, which can improve the efficacy and safety.

BACKGROUND: : Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors. METHODS: : Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed. RESULTS: : Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880). CONCLUSIONS: : Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years. TRIAL REGISTRATION : ChiCTR.org.cn, ChiCTR2100046766.
Breast Neoplasms/metabolism* ; Female ; Humans ; Ki-67 Antigen ; Mastectomy ; Receptor, ErbB-2/metabolism*

Objective:To analyze the statuses of CD8 + T cell exhaustion in patients with human immunodeficiency virus (HIV) infection, Mycobacterium tuberculosis (MTB) infection and co-infection. Methods:A total of 87 patients infected with HIV and/or MTB in Wuxi Fifth People′s Hospital and Taicang First People′s Hospital from August 2019 to January 2020 were enrolled, including 18 cases of HIV infection, 34 cases of active tuberculosis (ATB), 19 cases of latent tuberculosis infection (LTB), seven cases of HIV coinfected with ATB, and nine cases of HIV coinfected with LTB. Another 11 healthy controls were also included. The peripheral blood of all subjects was collected for cell surface staining and intracellular cytokine staining, and flow cytometry was used to detect the expressions of activation molecules including CD62 ligand, CD44 and CD127, the transcription factor like eomesodermin (EOMES), T cell factor 1 (TCF-1), T-box expressed in T cells (T-bet), B lymphocyte-induced maturation protein 1 (Blimp-1), inhibitory receptors including programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (Tim-3) on CD8 + T cells. Mann-Whitney U test was used for statistical analysis. Results:The mean fluorescence intensities (MFIs) of the activation molecules CD62 ligand and CD44 in the HIV group were lower than those in the healthy control group, while the inhibitory receptor Tim-3 was higher than that in the healthy control group. The differences were all statistically significant ( U=31.00, 1.00 and 0.00, respectively, all P<0.010). The MFIs of CD62 ligand and CD44 in HIV coinfected with LTB group were lower than those in LTB group, while PD-1 and Tim-3 were higher than those in LTB group. The differences were all statistically significant ( U=4.00, 26.00, 6.00 and 3.00, respectively, all P<0.010). The MFIs of CD62 ligand, CD44 and CD127 in HIV coinfected with ATB group were lower than those in ATB group, while PD-1 and Tim-3 were higher than those in ATB group. The differences were all statistically significant ( U=9.00, 40.00, 45.50, 28.00 and 7.00, respectively, all P<0.010). The proportion of terminal effector CD8 + T cells in the HIV group was higher than that in the healthy control group, while the proportion of central memory CD8 + T cells was lower than that in the healthy control group. The differences were both statistically significant ( U=15.00 and 33.00, respectively, both P<0.010). The proportion of terminal effector CD8 + T cells in the HIV coinfected with LTB group was higher than the LTB group, while the proportion of central memory CD8 + T cells was lower than that in the LTB group. The differences were both statistically significant ( U=7.00 and 20.00, respectively, both P<0.010). The proportion of terminal effector CD8 + T cells in the HIV coinfected with ATB group was higher than that in ATB group, while the proportion of central memory CD8 + T cells was lower than that in ATB group. The differences were statistically significant (both U=7.00, P<0.001). The expression level of PD-1 + Tim-3 + T cells in HIV group was higher than that in healthy control group, that in HIV coinfected with LTB group was higher than that in LTB group, and that in HIV coinfected with ATB group was higher than that in ATB group. The differences were all statistically significant ( U=21.00, 6.00 and 5.50, respectively, all P<0.001). The MFI of transcription factors EOMES and TCF-1 in HIV coinfected with LTB group were lower than those in HIV group, while the MFI of T-bet was higher than that in HIV group. The differences were all statistically significant ( U=3.00, 4.00 and 9.00, respectively, all P<0.001). The MFI of EOMES and TCF-1 in HIV coinfected with ATB group were lower than those in HIV group, while the MFI of T-bet and Blimp-1 were higher than those in the HIV group. The differences were all statistically significant ( U=11.00, 14.00, 7.00 and 22.00, respectively, all P<0.050). Conclusions:MTB co-infected with HIV patients present lower immune function and a higher degree of CD8 + T cell exhaustion. In addition, HIV patients co-infected with LTB and ATB have a higher degree of CD8 + T cell exhaustion than HIV infected patients.

Objective:To investigate the effect of long-term alcohol intake on sensory information synaptic transmission of mossy fiber-granular cells in the cerebellar cortex of mice.Methods:Twenty healthy male ICR mice aged 6 to 8 weeks were divided into normal saline group(control group) and alcohol intake group(alcohol group) according to random number table, with 10 mice in each group. The mice in alcohol group were injected intraperitoneally with 20% alcohol and the mice in control group were injected with the same amount of saline for 28 days.After the injection, the scalp, muscle tissue and skull were removed in turn, and the dura mater was removed to fully expose the crus II area of cerebellum. The mice were stimulated by air blowing at 30 mm of the ipsilateral tentacle pad with a gas jet device.When the the maximal response site was determined, the NMDA receptor antagonist (D-APV), metabolic glutamate receptor 1 antagonist (JNJ16259685) and N-methyl-D-aspartic acid (NMDA) were perfused on the brain surface of mice. Each drug was perfused for 20 minutes and ACSF was used between the two drugs until the waveform was recovered. Patch clamp amplifier was used to record the changes of potential waveform in mouse cerebellar granule layer. The data were analyzed by the softwares of Clampfit 10.3 and SPSS 22.0.Results:After exposure to wind stimulation, the latency of field potential response in granular layer of mice in alcohol group (11.8±0.7)ms was significantly longer than that in the control group (10.1±0.2)ms ( t=-8.041, P<0.05), and the amplitude of N1 (1.2±0.1) MV was significantly lower than that in the control group (0.6±0.1) MV ( t=-12.728, P<0.05). Compared with the control group, the rise time of P1 waveform((4.4±0.2)ms, (3.2±0.2)ms), duration ((12.1±0.5)ms, (10.3±0.2)ms), extinction time((7.8±0.2)ms, (6.9± 0.2)ms), volume under waveform ((7.3±0.2)ms, (4.3±0.2)ms) were significantly increased in the alcohol group ( t=16.100, - 11.840, -11.673, -35.576, all P<0.05). There were no significant differences in the amplitude, half width, rise time and decay time of Roff wave between the two groups ( t=-1.909, -0.910, -0.789, 1.462, all P>0.05). When JNJ16259685 was perfused on the brain surface of mice in alcohol group, the amplitude of field potential evoked by five blowing stimuli had no significant difference compared with that before administration (all P>0.05). When D-APV was perfused into the brain surface of mice in the alcohol group, the amplitude of P1 ((42.3±1.5) Mv)was significantly lower than that before administration ((101.1±0.9)mV) and after elution ((100.1±2.2) mV) ( t=106.762, - 69.605, both P<0.05), and the area under waveform of P1 ((42.6±1.3)%) was also significantly lower than that before administration ((100.6±1.6)%) and after elution ((97.6±2.2)%) ( t=88.862, -67.791, both P<0.05).The ratio of N2 / N1 (0.3±0.1) was significantly lower than that before administration (0.4±0.1) and after elution (0.3±0.1) ( t=2.242, 2.121, both P<0.05). When NMDA was perfused on the brain surface of mice in the control group, compared with before administration and after elution, the amplitude of P1 ((110.7±3.2) mV, (100.1±0.9) mV, (102.0±1.7) mV, t=-10.173, 7.669, both P<0.05), the area under the waveform of P1 ((127.9±3.5)%, (100.0±3.1)%, (115.0±5.3)%, t=-18.698, 6.447, both P<0.05), the ratio of N2 / N1 ((0.5±0.1), (0.3±0.1), (0.3±0.1), t=-5.669, 5.669, both P<0.05) were all significantly increased. When D-APV was perfused on the brain surface of mice in control group, the field potential evoked by blowing stimuli had no significant difference compared with that before administration and after elution (all P>0.05). Conclusion:Long-term alcohol intake significantly suppresses the synaptic transmission of excitatory glutamate in MF-GC, and enhances the inhibitory response mediated by GABAA receptor in cerebellar cortex. The inhibitory component is enhanced by NMDA receptor, but not by type 1 metabolic glutamate receptor.