Objective To report cases of checkpoint inhibitor pneumonitis （CIP） in patients with advanced biliary tract cancer, aiming to provide additional approaches for the assessment, treatment, and monitoring of this condition. Methods Three patients developed oxygen desaturation and interstitial lung lesions during chemotherapy combined with immunotherapy, and were diagnosed with CIP in collaboration with the respiratory department. Antitumor therapy was discontinued in the acute phase, and glucocorticoids were administered, with regular monitoring of disease progression. During follow-up, case 1 developed lung metastasis; case 2 showed improvement; case 3 had concurrent infection and tumor progression. Results Glucocorticoids improved lung lesions and hypoxic symptoms in patients with CIP, but attention should be paid to the potential for concurrent infections and tumor progression. Conclusions Comprehensive assessment and early identification of CIP are crucial for patients with advanced biliary tract cancer. For those with recurrent symptoms after glucocorticoid therapy, timely and accurate adjustment of the treatment regimen is essential.

Objective To investigate the distributions of vitamin K1 and K2 in infants of different age groups by comparing the serum levels of vitamin K1 and K2 in them.Methods 1177 infants from 0 to 3 months were divided into 6 age groups.Those born/treated in the subject units(pediatrics,neonatology,child health care,obstetrics)were selected as the study subjects and grouped by age:0～3 days(591 cases),4～7 days(255 cases),8～5 days(104 cases),1 month(118 cases),2 months(40 cases),and 3 months(69 cases).General data of the infants were collected,and the serum vitamin K1 and K2 levels were determined by HPLC-mass spectrometry(LC-MS)on a unified platform,and analyzed from the distribution of vitamin K1 and K2 at different ages.Results The distributions of vitamin K1 and K2 levels were statistically significant(P<0.001);newborns were highly vulnerable to vitamin K1 deficiency,and vitamin K2 deficiency was higher than vitamin K1 with age.Conclusion Maintaining the normal growth of vitamin K1 and K2 is crucial for the normal growth and development of infants of all ages,so we should pay close attention to the monitoring and supplement of vitamin K1 and K2.

Objective:To explore the anti-inflammatory effect and safety of two non-steroidal anti-inflammatory drugs in the phacoemulsification combined with intraocular lens (IOL) implantation.Methods:A randomized, double-blind, clinical trial was conducted.A total of 90 age-related cataract patients (90 eyes) who were diagnosed in Qingdao Eye Hospital Affiliated to Shandong First Medical University were enrolled from October 2020 to February 2021.The patients were randomized to diclofenac sodium group and bromofenac sodium group by random number table method, with 45 cases (45 eyes) in each group.All patients underwent phacoemulsification combined with IOL implantation, and 0.1% diclofenac sodium eye drops (preservative-free), 4 times a day, and 0.1% pramiphene eye drops, 2 times a day were applied in the perioperative period.The duration of continuous medication treatment and follow-up time were 6 weeks.The subjective symptoms of the patients were scored before and after surgery.The amount of tear fluid secretion was detected by Schirmer I test, and the tear film breakup time was recorded with the Oculus dry eye analyzer.Corneal fluorescein staining was observed under a slit lamp microscope with cobalt blue light.Anterior chamber flash was measured by slit-lamp biomicroscopy.The thickness of central macular area and the presence of macular cystoid edema was measured by optical coherence tomography.Visual acuity, noncontact intraocular pressure (IOP) and the drug safety were examined and evaluated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Qingdao Eye Hospital (No.[2020]60).All patients were informed about the surgery and postoperative medication and signed the informed consent form.Results:All subjects had no intraoperative complications, and completed treatment and follow-up as required.The preoperative, 1-day postoperative, 1-week postoperative, 6-week postoperative subjective symptom scores were (0.47±0.73), (0.56±0.62), (0.33±0.48), and (0.51±0.66) points in the diclofenac group, and (0.47±0.51), (0.75±0.61), (0.64±0.65), and (0.78±0.77) points in the bromfenac group.There were statistically significant differences in the subjective symptom scores at different time points between the two groups ( Fgroup=5.001, P=0.028; Ftime=2.920, P=0.035), and the subjective symptom scores of diclofenac sodium group were significantly lower than those of bromofenac sodium group (all at P<0.05).The preoperative, 1-week postoperative, 6-week postoperative tear secretion volume were (5.87±2.37), (6.07±2.53), and (6.29±0.25) mm in diclofenac sodium group, and (7.36±2.74), (6.29±3.46), and (5.80±2.76) mm in bromofenac sodium group.There was statistically significant difference in the tear secretion volume between the two groups before surgery ( F=6.910, P=0.012), but there was no significant difference on postoperative weeks 1 and 6 ( F=1.121, 0.772; P=0.729, 0.384).The preoperative, 1-week postoperative, 6-week postoperative non-invasive tear break-up time (NIBUT) were (8.00±6.28), (6.68±5.24), and (6.17±5.00) seconds in diclofenac sodium group, and (6.40±5.28), (4.50±2.46), and (5.39±5.39) seconds in bromofenac sodium group.There was no significant difference in NIBUT between the two groups ( Fgroup=3.415, P=0.068).There was significant difference in NIBUT within groups among different time points ( Ftime=4.358, P=0.020).The 1-day postoperative, 1-week postoperative, 6-week postoperative corneal epithelial staining score were (1.40±0.81), (0.13±0.34), (0.00±0.00) points in diclofenac sodium group, and (1.38±0.89), (0.22±0.47), and (0.00±0.00) points in bromofenac sodium group.There was no statistically significant difference in the corneal epithelial staining score between the two groups after surgery ( Fgroup=0.110, P=0.741).There were statistically significant differences in corneal epithelial staining scores within groups among different time points ( Ftime=175.054, P<0.01).The 1-day postoperative, 1-week postoperative, 6-week postoperative anterior chamber flare classification were 1.13±0.51, 0.13±0.34, and 0.00±0.00 in diclofenac sodium group, and 1.02±0.34, 0.16±0.37, and 0.00±0.00 in bromofenac sodium group.There was no significant difference in the overall anterior chamber flash between the two groups ( Fgroup=0.045, P=0.507).There were statistically significant differences in anterior chamber flash within groups among different time points ( Ftime=322.331, P<0.001).There was no significant difference in the preoperative and 6-week postoperative macular fovea thickness between both groups ( t=-0.221, -0.374; both at P>0.05).The incidence of macular cystoid edema 6 weeks after operation was 0% in both groups.Subjects tolerated the two tested drugs well.Eight adverse events occurred in this study, all of which were mild postoperative IOP elevation, including 3 in diclofenac sodium group with an incidence of 6.67% and 5 in bromofenac group with an incidence of 11.1%.IOP returned to normal in all the patients 1 week after stopping the use of drug. Conclusions:Two nonsteroidal anti-inflammatory drugs are safe and effective for anti-inflammatory treatment after cataract phacoemulsification combined with IOL implantation.The new diclofenac sodium eye drops are more comfortable than bromfenac sodium eye drops.

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.

BACKGROUND:The specific molecular mechanism of the transformation from normal healthy people to acute cervical spondylotic radiculopathy has not been clear,which needs to be further studied. OBJECTIVE:To investigate the differential expression of serum proteomics between normal healthy people and patients with acute cervical spondylotic radiculopathy,and to find and identify potential specific serum markers between them. METHODS:The serum samples of eight patients with acute cervical spondylotic radiculopathy and eight normal healthy people were collected,and the proteomic screening and analysis were performed by tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology,in order to explore and identify serum proteins differentially expressed in patients with acute cervical spondylotic radiculopathy. RESULTS AND CONCLUSION:A total of 183 significantly differential proteins were screened by tandem mass tag technology,and 11 significantly differential proteins were identified(P＜0.05).Compared with normal healthy people,three differential proteins were significantly up-regulated,including human leukocyte antigen-A,secretoglobin family 1a member 1,and protein 4-hydroxyphenylpyruvate dioxygenase,and seven differential proteins were significantly down-regulated,such as immunoglobulin heavy constant gamma 3,skin factor,and myosin light chain 3,in patients with acute cervical spondylotic radiculopathy.Gene ontology enrichment analysis showed that these differential proteins participated in antigen binding,immunoglobulin receptor binding and other molecular functions.Protein-protein interaction analysis showed that among the common differential proteins between normal healthy people and patients with acute cervical spondylotic radiculopathy,HLA-A,HPD,PSMA3,DMKN,SCGB1A1,and MYL3 were located at the nodes of the functional network,and were closely related to the systems of body immunity,cellular inflammatory response,energy metabolism,and mechanical pressure.The significantly differential proteins HLA-A,HPD and MYL3 were verified by western blot,and the results were consistent with those of proteomics.To conclude,tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology can be used to find the differentially expressed proteins in serum between normal healthy people and patients with acute cervical spondylotic radiculopathy.It is preliminarily believed that HLA-A,HPD and MYL3 may be specific serum markers of acute cervical spondylotic radiculopathy,providing a new direction for further research on its pathogenesis.

BACKGROUND:Previous studies have found that qi deficiency and blood stasis syndrome is the main syndrome among various TCM syndromes of cervical spondylotic myelopathy.However,there is no report on proteomic markers as early diagnosis indicators for the transformation of developmental cervical spinal stenosis with qi deficiency and blood stasis syndrome to cervical spondylotic myelopathy. OBJECTIVE:To explore serum proteomics difference between developmental cervical spinal stenosis and cervical spondylotic myelopathy and to find and identify the potential serum biomarkers between them. METHODS:Serum samples of nine patients with cervical spondylotic myelopathy of qi deficiency and blood stasis syndrome(experimental group)and nine patients with developmental cervical spinal stenosis of qi deficiency and blood stasis syndrome(control group)were collected.The proteomic analysis was carried out by Tandem Mass Tag combined with liquid chromatography tandem mass spectrometry,so as to find and identify differentially expressed proteins. RESULTS AND CONCLUSION:A total of 1027 significantly differential proteins were initially screened by TMT technology and 89 significantly differential proteins were finally identified(P<0.05).Compared with the control group,there were 45 up-regulated proteins in the experimental group,such as α-actinin-4,α-actinin-1,cell division control protein 42 homolog,integrin-linked protein kinase and B-actin.Conversely,there were 44 down-regulated proteins in the experimental group compared with the control group,such as fibronectin,fibrinogen γ chain,fibrinogen α chain,fibrinogen β chain.Gene ontology enrichment analysis indicated that these differential proteins were involved in signal receptor binding,kinase binding,protein kinase activity,integrin binding,actin filament binding and other molecular functions.Based on the Kyoto Encyclopedia of Genes and Genomes pathway analysis,20 common differential signal/metabolic pathways were identified,including Rap1 signaling pathway,adherens junction,tight junction,platelet activation,and regulation of actin cytoskeleton.Protein-protein interaction analysis showed that ILK,FGA,FGB,FGG,FN1,Cdc42,ACTN1,ACTN4 and ACTB were located at the nodes of protein-protein interaction network and were closely related to bone formation and destruction system,nervous system,coagulation system,cellular inflammation and other systems.To conclude,the serum differentially expressed proteins between developmental cervical spinal stenosis and cervical spondylotic myelopathy can be successfully screened by Tandem Mass Tag combined with liquid chromatography tandem mass spectrometry.ILK,FN1,CDC42 and ACTN 4 are identified as specific markers for the transformation of developmental cervical spinal stenosis with qi deficiency and blood stasis syndrome into cervical spondylotic myelopathy.These findings provide a basis for further clarifying the transformation mechanism.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

【Objective】 To compare the effects of 3 rehydration methods before blood donation on the prevention of on-site and delayed blood donation-related vasovagal response (VVR) . 【Methods】 From January to June 2021, 6 250 whole blood donors in 6 fixed blood donation sites signed informed consent and were divided into 198 clusters according to donor sites and dates, then they were randomly assigned to receive either oral rehydration salts (ORS), sugar water, or water group, and each drank 500 mL of ORS, sugar water or water within 20 minutes before blood donation. The researchers recorded the actual intervention accepted on site, and recorded the immediate VVR and related information. At rest after blood donation, donors submitted an electronic questionnaire containing socio-demographic information. At 48 hours after blood donation, the researchers called back every donor to record delayed VVR and related information. Logistic regression based on intention to treat (ITT) was used to analyze the difference of the incidence of VVR among the three groups, and the average treatment effect on treated (ATT) was calculated. PASS 2021was used to estimate the sample size and R (4.2.0) for statistical analysis. 【Results】 The cumulative incidence of blood donation-related VVR was 2.67% (2.29%-3.11%) among street whole blood donors under the 3 rehydration methods, in which, the incidence of immediate and delayed VVR was 1.02% (0.79%-1.31%) and 1.65% (1.36%-2.01%) respectively. ITT analysis found that ORS were more effective than water in reducing the incidence of delayed VVR【OR=0.59,95% CI[0.37,0.94]】.There was no significant difference in the incidence of immediate VVR between any two groups (P > 0.05), and there was no significant difference in the incidence of delayed VVR in the sugar water group compared with the water group (P > 0.05). There was a difference of -0.013 (【95% CI[-0.022, -0.004]】or -0.008【95% CI[-0.017, -0.000]】in the incidence of delayed VVR in the ORS group compared with water group or sugar water group, the difference was significant (P<0.05). The cumulative VVR of the three groups showed similar results to the delayed VVR. 【Conclusion】 Drinking ORS before blood donation is the most effective rehydration method to prevent delayed VVR. The next step is to establish the predictive model of delayed VVR to screen the susceptible population and provide them with ORS before blood donation, while other population can choose any liquid they like, thus achieving personalized blood donation-related VVR prevention and control.

Objective:To compare the efficacy of endoscopic submucosal dissection (ESD) and modified-endoscopic mucosal resection (M-EMR) for G1 rectal neuroendocrine tumors (RNETs) .Methods:Data of 121 patients with pathologically confirmed G1 RNETs treated with ESD ( n=105) or M-EMR ( n=16) in Nanjing Drum Tower Hospital from January 2017 to September 2020 were retrospectively analyzed. The complete resection rate, complication incidence, hospital stay, treatment cost and other indicators of the two groups were compared by using inverse probability of treatment weighting (IPTW). Results:There were significant differences in tumor number ( χ2=8.76, P=0.003), tumor invasion depth ( χ2=6.96, P=0.008), utilization of metal clips [82.9% (87/105) VS 93.8% (15/16), χ2=8.78, P=0.003], number of metal clips ( χ2=8.41, P=0.016), hemostasis using hot clamp [78.1% (82/105) VS 18.7% (3/16), χ2=20.64, P<0.001], traction procedure [2.9% (3/105) VS 18.7% (3/16), χ2=4.45, P=0.035] and treatment cost (17 568.6 ± 8 911.0 yuan VS 8 120.8±1 528.2 yuan, t=3.65, P<0.001) between the ESD group and the M-EMR group. After verifying the stability of the results using IPTW sensitivity analysis, there was still significant difference in the treatment cost ( t=2.07, P<0.001). Conclusion:Both ESD and M-EMR demonstrate comparable efficacy in treating G1 RNETs; however, M-EMR exhibites lower treatment costs.