BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

ObjectiveTo investigate the levels of neutralizing antibodies against the novel coronavirus in the serum of elderly individuals aged 60 years and above in Shanghai’s Changning District， following natural infection and mixed immunity， in order to provide a basis for strengthening immunity in the elderly. MethodsElderly people who participated in free health check-ups at 10 community health service centers in Changning District from May to June 2023 were selected as the subjects. Information such as gender， age， COVID-19 infection history， COVID-19 vaccine immunization history， and chronic disease history were collected. Serum samples of the subjects were collected and quantitative detection of SARS-CoV-2 neutralizing antibodies was performed by magnetic particle chemiluminescence method. The antibody levels of different populations were analyzed. ResultsA total of 620 subjects were included， 586 of whom （241 males and 345 females） met the study conditions. There were 90 people in the full vaccination + infection group， 224 people in the intensive vaccination + infection group， and 272 people in the unvaccinated + infection group. The positive rates of COVID-19 antibody in the three groups were 94.44% （95%CI： 87.51%‒98.17%）， 95.98% （95%CI：92.51%‒98.15%） and 22.06% （95%CI： 17.28%‒27.46%）， respectively. The positive rates in full vaccination + infection group and intensive vaccination + infection group was significantly higher than that in unvaccinated + infection group （χ²=147.561，P<0.01；χ²=271.729，P<0.01）. The antibody level in full vaccination + infection group （640.74 AU·mL^-1） and intensive vaccination + infection group （1 200.88 AU·mL^-1） was significantly higher than that in unvaccinated + infection group （4.51 AU·mL^-1） （all P<0.01）.The antibody level in the intensive vaccination + infection group was also significantly higher than that in the whole vaccination + infection group （P < 0.05）. ConclusionAfter 5‒6 months of infection， the neutralizing antibody positive rate and antibody level were significantly higher in the elderly who received the full vaccination and infection or intensive vaccination and infection. It is recommended that elderly individuals， who have been infected for more than 5‒6 months but have not been vaccinated， should consider getting vaccinated to enhance their levels of neutralizing antibodies.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective: To investigate the clinical features, morphological characteristics, immunophenotype, and differential diagnosis of goblet cell adenocarcinoma (GCA) in the digestive system. Methods: The clinicopathological data, morphological characteristics, immunophenotypes of 22 cases of GCA in the digestive system diagnosed from January 2010 to January 2021 were collected. Meanwhile, 25 cases of neuroendocrine neoplasm (NEN) and 24 cases of adenocarcinoma were used as controls. Relevant literature was also reviewed. Results: There were 16 males and 6 females, aged from 36 to 79 years with an average of 56 years. The anatomical sites of the 22 GCA were mostly appendix (17 cases) and occasionally extra-appendix (5 cases), including 3 cases in stomach, 1 case in duodenum and 1 case in anal. All 17 cases of appendiceal GCA were pure GCA. Among the 5 cases of extra-appendiceal GCA, One case of gastric GCA was pure, two cases of gastric GCA with NEN or adenocarcinoma, duodenal GCA with NEN and adenocarcinoma, anal GCA with NEN.Low-grade GCAs were composed of goblet, Paneth and neuroendocrine cells, which were arranged in intestinal crypt tubular or cluster structures and distributed in the wall of digestive system. The tubular and cluster structures lacked adhesion. Goblet cells were columnar, located in the base, with clear cytoplasm, small nuclei, inconspicuous atypia, and uncommon mitoses. Extracellular mucus and signet-ring cells with nuclear variations could be seen in some cases. Nerve fiber bundle invasion and tumor thrombus in vessels were often present. High-grade GCAs lacked tubular and cluster structures, and their histological structures were more complex. Tumor cells expressed mixed neuroendocrine and glandular epithelial markers. Similar to the expression patterns of synaptophysin and chromogranin A, CD200 and INSM1 were also dot-like or patch-positive in GCA. Conclusions: GCA is an infrequent tumor of the digestive system and shows the bi-directional differentiation characteristics of neuroendocrine and glandular epithelium. Accurate diagnosis and staging are related to its prognosis.
Adenocarcinoma/pathology* ; Appendiceal Neoplasms/surgery* ; Carcinoid Tumor/surgery* ; Chromogranin A ; Female ; Goblet Cells/pathology* ; Humans ; Male ; Neuroendocrine Tumors/pathology* ; Repressor Proteins ; Synaptophysin

Objective:To investigate the clinical efficacy of different grade transoral atlantoaxial release for the treatment of irreducible atlantoaxial dislocation.Methods:From January 2010 to December 2019, 297 patients with irreducible atlantoaxial dislocation treated by different grade releases were retrospectively analyzed, including 132 males and 165 females, aged 42.3±12.14 years (range, 10-63 years). All cases were treated by different grade releases, Grade I (196, 66.0%), Grade II (54, 18.2%), Grade III (28, 9.4%) and Grade IV (19, 6.4%). The American Spinal Injury Association (ASIA) grade and Japanese Orthopedic Association (JOA) score were recorded as the clinical evaluation index. The clivus-canal angle (CCA) and cervico-medullary angle (CMA) were measured to evaluate the reduction. The surgery time, blood loss, duration of bony fusion and complications were also analyzed.Results:The follow-up time was 14.8±10.2 months (range, 9-36 months). The surgery time of Grade I-IV were 2.02±0.35 min, 3.00±0.36 min, 4.07±0.96 min and 5.24±0.83 min, respectively ( F=385.43, P<0.001), blood loss was 84.08±27.21 ml, 153.61±31.36 ml, 268.93±48.94 ml and 444.21±109.51 ml, respectively ( F=582.39, P<0.001). The preoperative ASIA motor score of Grade I-IV were 83.85±6.68, 84.06±5.47, 84.07±5.99 and 85.00±4.11, respectively. The last follow-up were 98.34±2.38, 98.67±1.79, 98.86±1.58 and 98.32±2.11, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative JOA score of Grade I-IV were 11.44±1.73, 11.59±1.72, 11.61±1.47 and 11.32±1.80, respectively. The last follow-up were 16.22±1.00, 16.28±1.02, 16.14±1.04 and 16.16±1.07, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CCA of Grade I-IV were 110.19°±8.76°, 112.48°±7.66°, 106.61°±6.54° and 109.05°±7.79°, respectively. The last follow-up were 140.22°±8.04°, 141.86°±7.04°, 142.35°±8.62° and 140.15°±6.49°, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CMA of Grade I-IV were 113.48°±9.54°, 116.03°±8.38°, 109.55°±7.13°, and 112.46°±8.33°, respectively. The last follow-up were 144.28°±7.75°, 146.40°±6.98°, 145.81°±8.27° and 143.24°±6.36°, respectively, with statistically significant differences from preoperative ( P<0.05). Solid bony fusion was obtained except for 3 cases, the fusion time was 9.71±2.55 months (range 3-14 months). Altogether 33 complications occurred in all cases (11.1%), including 3 fusion failure, 3 cerebrospinal leak, 3 wound infection, 2 death (1 case caused by cerebrospinal leak), 11 pharyngeal discomfort, 4 postoperative pain surrounding iliac crest, and 8 malunion of iliac crest. Conclusion:Transoral stepped atlantoaxial release theory could provide guidelines for atlantoaxial dislocation treatment, and make the transoral release technique more effective and safer.

Background: Bone metastases are common in patients with advanced cancer. Bisphosphonates (BPs) could prevent or delay the development of skeleton-related events (SREs). The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases. Methods: Consecutive cancer patients who had bone metastases and received BP treatment were enrolled. A ques-tionnaire was developed to collect the patients’clinical data, as well as information on the diagnosis and manage-ment of bone metastases. Physicians’awareness of the guidelines and knowledge of the application of BP were also assessed. Results: A total of 3223 patients with lung cancer (36.5%), breast cancer (30.9%), prostate cancer (8.5%), and gas-trointestinal cancer (5.7%) were included in this study. The sites of bone metastases were the thoracic spine (56.0 %), lumbar spine (47.1%), ribs (32.6%), and pelvis (23.2%). The SRE frequency was the highest in patients with multiple myeloma (36.6%), followed by those with lung cancer (25.9%), breast cancer (20.2%), prostate cancer (18.2%), and gas-trointestinal cancer (17.3%). Irradiation to the bone was the most frequent SRE (58% in lung cancer patients, 45% in breast cancer patients, and 48% in prostate cancer patients). Our survey also showed that 45.5% of patients received BP within 3 months after their diagnosis of bone metastases, whereas the remaining 54.5% of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases. The SRE frequency in the former group was significantly lower than that in the latter group (4.0% vs. 42.3%, P < 0.05). In patients with more than 6 months of continuous BP treatment, the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment (7.2 vs. 3.4 months, P < 0.05). In addition, 12.2% of the physicians were not aware of the efcacy of BP in preventing and delaying SRE. Only half (52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable. Conclusions: Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs. However, our survey also revealed that the proper application of BP was not as common as expected in China.

For decades, the selection of chemotherapeutic regimens for the treatment of recurrent or metastatic nasopharyn-geal carcinoma has been mainly empirical. To our knowledge, there is no phase 3 trial that has been conducted to determine the optimal treatment for these patients before our publication. Recently, we published an article inThe Lancet entitled “Gemcitabine plus cisplatin versus lfuorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial.” The results of our study indicate that gemcitabine plus cisplatin could improve the survival of patients with recurrent or metastatic nasopharyngeal carcinoma com-pared with conventional lfuorouracil plus cisplatin.

Objective To explore the association between the ABO blood group and the risk of myocardial infarction in Chinese people.Methods We retrospectively recruited 1 988 consecutive patients with acute myocardial infarction (AMI) and 1 856 non-coronary artery disease (non-CAD) subjects who hospitalized in our hospital between January 2013 and December 2013.The clinical features and ABO blood group were analyzed.Results Blood group distribution was A (27.1％,539/1 988),B (34.4％,684/1 988),AB(10.8％,215/1 988),O (27.7％,551/1 988) in patients with AMI and A (26.7％,496/1 856),B(32.2％,598/1 856),AB (10.8％,200/1 856),O (30.4％,564/1 856) in non-CAD group.The single factor analysis showed that blood group O tended to be more common in the non-CAD group than in AMI group (P =0.06).After adjustment for common cardiovascular risk factors such as age,gender,hypertension,diabetes,smoking and serum cholesterol level,the A,B,and AB blood groups were associated with increased risk of AMI compared with O blood group,and the difference was significant with A blood group (OR =1.229,95％ CI 1.019-1.482,P =0.031) and B blood groups (OR =1.214,95％ CI 1.017-1.449,P =0.032).In addition,non-O blood group remained significantly associated with the increased risk of AMI than O blood group after logistic regression analysis(OR =1.223,95％ CI 1.048-1.426,P =0.01).Conclusion Our results suggest that non-O blood group is associated with the increased risk of AMI.

Objective To explore mRNA and protein expression of PAl-1 in kidney tissue of mice with IgA nephropathy (IgAN) and the effects of YiShen Decoction. Methods The IgAN model was built by the method of oral intake of bovine serum albumin(BSA)together with the injection of staphylococcus enterotoxin B(SEB)through caudal vein. The mRNA expression of PAI-1 was measured by fluorescent quantitative polymerase chain reaction (FQ-PER)and the expression of PAI-1 protein was measured by immunohistochemistry. Results No significant difference of mRNA and protein expression of PAI-1 was found between the low concentration and high concentration Yishen Decoction group. But the secretion and mRNA expression of PAI-1 in the low and hiigh concentration Yishen Decoction group was decreased more than that in the IgAN model group. Conclusion The abnormal expression of PAI-1 mRNA and protein played an important role in the onset and development of IgAN. The TCM Yishen Decoction could reduce the abnormal expression of the mRNA and protein of PAI-1 in kidney tissue of mice with IgA nephropathy.

BACKGROUND:Cerebrovascular drag, occlusion and other mechanical stimulations inevitably occur during some craniocerebral operations, which cause acute mechanical cerebrovascular vasospasm. At present, the mechanism underlying the patho-physiology as well as the pathological prognosis of this acute mechanical vasospasm remains unclear.OBJECTIVE: To observe changes in the vascular diameter of the middle cerebral artery, cerebral blood flow (CBF), and ultrastructure of vascular wall and vascular endothelial cells, during the early stage (2 hours) of mechanical cerebral vasospasm in cats.DESIGN: Open experiment.SETTING: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; Beijing Institute of Neurosurgery.MATERIALS: Six healthy adult hybrid cats, of either gender, weighing from 2.5 to 3.5 kg, were provided by the China Medical Science Institute of Experimental Animals. Laser Doppler flowmetry (Periflux 5010, Sweden Perimed Company)was used.METHODS: This study was carried out in the Beijing Institute of Neurosurgery between August 2005 and March 2006. For all experimental surgical procedures, the cats were anesthetized by intraperitoneal injection of 200 g/L chloral hydrate, at 2 mL/kg, and then placed in a prone position. A median incision was made in the scalp and a square bone window, 8×10 mm, was opened at 1.5 cm posterior and 1.5 lateral to the anterior fontanel, after which the dura mater was pricked out. The fine detecting head of the Laser Doppler flowmetry was fixed to a region of the cerebral surfacewith no vessels or with only a few vessels. Subsequently, the cats were placed in lateral position. Under the surgical microscope, the right middle cerebral artery was exposed through a suborbital approach. Blunt apparatus was used to stimulate middle the middle cerebral artery repeatedly, at a frequency of 100 time/min within 30 minutes.The diameter of the middle cerebral artery was measured and a perfusion index of cortical brain tissue was monitored, separately, before and then at 0, 0.5, 1.0, 1.5, 2.0 hours after stimulation. Ultrastructural changes in the vascular wall and the vascular endothelial cells were observed during the early stage (2 hours) of mechanical cerebral vasospasm in cats.MAIN OUTCOME MEASURES: Diameter of the middle cerebral artery and the perfusion index of cortical brain tissue before and then at 0, 0.5, 1.0, 1.5, 2.0 hours after stimulation, as well as any ultrastructural changes in the vascular wall and endothelial cells 2 hours after stimulation.RESULTS: The results from six cats were were analyzed. ①The diameter of the middle cerebral artery was (0.617±0.129), (0.723±0.082), (0.840±0.084) mm 0, 0.5 and 1.0 hours after stimulation, respectively, which was significantly smaller than that before stimulation [(0.897±0.066) mm,t =4.74, 4.017, 1.299,P ＜ 0.01]. ② The perfusion index of cortical brain tissue was 67.8±18.5, 82.5±17.5, 89.8±24.0, 94.0±22.2 and 98.5±21.0 at 0, 0.5, 1.0,1.5 and 2.0 hours after stimulation, which was significantly lower than that before stimulation (159.2±23.5, t =4.716-7.469, P ＜ 0.01 ). ③ At the early stage of acute mechanical stimulation (2 hours) to middle cerebral artery, endothelial cell chromatin aggregated at the edge of the cells and achromocyte formed, but mitochondrial crista was unclear.CONCLUSION: Mechanical stimulation to the middle cerebral artery in cats can lead to cerebral vasospasm. Apoptosis of endothelial cells appears at the early stage of stimulation (2 hours). These results indicate that, in order to prevent against cerebral vasospasm, cerebrovascular mechanical stimulation should be as minimal as possible and that as few as possible craniocerebral operations should be performed.