Objective:To observe the clinical efficacy of acupuncture combined with cognitive training in treating mild-to-moderate poststroke cognitive impairment and the impact on cognitive function and cerebral blood flow.Methods:Eighty-eight participants with mild-to-moderate cognitive impairment after a stroke were allocated to an observation group and a control group using the random number table method,each consisting of 44 cases.The two groups received the same conventional symptomatic treatment.In addition,the control group was intervened by cognitive training,and the observation group by cognitive training and Tong Du Xing Shen(unblocking the Governor Vessel and awakening the mind)acupuncture.The intervention lasted 4 weeks in both groups.By the end of the intervention,the two groups were observed for clinical efficacy and the improvements in the symptom score of traditional Chinese medicine(TCM),cognitive function[mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)],cerebral blood flow velocities[cerebral vascular resistance index(RI),arterial blood flow mean velocity(Vm),and arterial systolic velocity(Vs)],and serum biomarkers of neurological deficit[neuron-specific enolase(NSE)and S100 β protein(S100β)].Results:During the observation,each group had 2 eliminated cases.After the intervention,the observation group achieved a total effective rate of 90.5%,higher than that in the control group,which was 73.8%(P<0.05);increases were found in the MMSE and MoCA scores in both groups(P<0.05),and the observation group was higher than the control group(P<0.05);in contrast,decreases were found in the levels of RI and serum NSE and S100β(P<0.05),and the observation group was lower than the control group(P<0.05);the Vs and Vm levels increased in both groups(P<0.05)and were higher in the observation group than in the control group(P<0.05).Conclusion:Tong Du Xing Shen acupuncture plus cognitive training is effective in treating mild-to-moderate poststroke cognitive impairment and can enhance the patient's cognitive function;improving cerebral blood circulation and reducing cerebral nerve damage may be involved in the mechanism.

Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

Objective:To observe the clinical efficacy of acupuncture combined with cognitive training in treating mild-to-moderate poststroke cognitive impairment and the impact on cognitive function and cerebral blood flow.Methods:Eighty-eight participants with mild-to-moderate cognitive impairment after a stroke were allocated to an observation group and a control group using the random number table method,each consisting of 44 cases.The two groups received the same conventional symptomatic treatment.In addition,the control group was intervened by cognitive training,and the observation group by cognitive training and Tong Du Xing Shen(unblocking the Governor Vessel and awakening the mind)acupuncture.The intervention lasted 4 weeks in both groups.By the end of the intervention,the two groups were observed for clinical efficacy and the improvements in the symptom score of traditional Chinese medicine(TCM),cognitive function[mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)],cerebral blood flow velocities[cerebral vascular resistance index(RI),arterial blood flow mean velocity(Vm),and arterial systolic velocity(Vs)],and serum biomarkers of neurological deficit[neuron-specific enolase(NSE)and S100 β protein(S100β)].Results:During the observation,each group had 2 eliminated cases.After the intervention,the observation group achieved a total effective rate of 90.5%,higher than that in the control group,which was 73.8%(P<0.05);increases were found in the MMSE and MoCA scores in both groups(P<0.05),and the observation group was higher than the control group(P<0.05);in contrast,decreases were found in the levels of RI and serum NSE and S100β(P<0.05),and the observation group was lower than the control group(P<0.05);the Vs and Vm levels increased in both groups(P<0.05)and were higher in the observation group than in the control group(P<0.05).Conclusion:Tong Du Xing Shen acupuncture plus cognitive training is effective in treating mild-to-moderate poststroke cognitive impairment and can enhance the patient's cognitive function;improving cerebral blood circulation and reducing cerebral nerve damage may be involved in the mechanism.

Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

AIM: To investigate t h e impacts of theaflavins (TFs) on neuronal apoptosis and blood-brain barrier (BBB) by regulating the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)/5 '-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. METHODS: Ninety rats were randomly separated into sham operation group, model group, low-dose TFs group (20 mg/kg TFs), high-dose TFs group (40 mg/kg TFs), and high-dose TFs + STO-609 group (40 mg/kg TFs + 10 ΜL CaMKK2 inhibitor-STO-609), positive control group (2 mg/kg nimodipine injection), with 15 rats in each group. A rat model of intracerebral hemorrhage was induced by collagenase type VII. The behavior of rats and the water content of brain tissue were detected; the serum of rats was isolated, and the levels of inflammatory factors-vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were detected; brain tissue around the hematoma was collected to detect neuronal apoptosis, BBB permeability parameter-EB level, and expressions of p-CaMKK2/CaMKK2, p-AMPK/AMPK and apoptosis-related protein Bax. RESULTS: Compared with the sham operation group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain tissue water content, apoptosis rate, EB level and Bax protein expression in the model group were all increased, both pCaMKK2/CaMKK2 and p-AMPK/AMPK were decreased (P < 0.05); compared with the model group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain water content, apoptosis rate, EB level and Bax expression in the low- and high-dose TFs groups and the positive control group were all lower than those in the model group, both pCaMKK2/CaMKK2 and p-AMPK/AMPK were increased (P < 0.05); compared with the high-dose TFs group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain tissue water content, apoptosis rate, EB level and Bax expression were all increased in the high dose TFs + STO-609 group, both p-CaMKK2/CaMKK2 and p-AMPK/AMPK were decreased (P < 0.05). CONCLUSION: TFs can reduce neuronal apoptosis, inflammatory response, BBB permeability, and play a protective role in rats with cerebral hemorrhage injury. Its mechanism is related to the activation of CaMKK2/AMPK signaling pathway.

Objective:To evaluate the effectiveness of deep learning reconstruction (DLR) compared with hybrid iterative reconstruction (Hybrid IR) in improving the image quality in chest low-dose CT (LDCT).Methods:Seventy-seven patients who underwent LDCT scan for physical examination or regular follow-up in Peking Union Medical College Hospital from October 2020 to March 2021 were retrospectively included. The LDCT images were reconstructed with Hybrid IR at standard level (Hybrid IR Stand) and DLR at standard and strong level (DLR Stand and DLR Strong). Regions of interest were placed on pulmonary lobe, aorta, subscapularis muscle and axillary fat to measure the CT value and image noise. The signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated. Subjective image quality was evaluated using Likert 5-score method by two experienced radiologists. The number and features of ground-glass nodule (GGN) were also assessed. If the scores of the two radiologists were inconsistent, the score was determined by the third radiologist. The objective and subjective image evaluation were compared using the Kruskal-Wallis test, and the Bonferroni test was used for multiple comparisons within the group.Results:Among Hybrid IR Stand, DLR Stand and DLR Strong images, the CT value of pulmonary lobe, aorta, subscapularis muscle and axillary fat had no significant differences (all P>0.05), but the image noise and SNR of pulmonary lobe, aorta, subscapularis muscle and axillary fat had significant differences(all P<0.05), and the CNR of images had significant difference( P<0.05), too. The CNR of Hybrid IR Stand images, DLR stand images and DLR strong images were 0.71 (0.49, 0.88), 1.06 (0.78, 1.32) and 1.14 (0.84, 1.48), respectively. Compared with Hybrid IR images, DLR images had lower objective and subjective image noise,higher SNR and CNR (all P<0.05). The scores of DLR images were superior to Hybrid IR images in identifying lung fissures, pulmonary vessels, trachea and bronchi, lymph nodes, pleura, pericardium and GGN (all P<0.05). Conclusions:DLR significantly reduced the image noise, and DLR images were superior to Hybrid IR images in identifying GGN in chest LDCT while maintaining superior image quality at relatively low radiation dose levels. Thus DLR images can improve the safety of lung cancer screening and pulmonary nodule follow-up by CT.

Objective:To explore the effect of deep learning reconstruction (DLR) on radiation dosage reduction and image quality of CTPA compared with hybrid iterative reconstruction (HIR).Methods:A total of 100 patients with suspected pulmonary embolism (APE) or indications for CTPA due to other pulmonary artery diseases in Peking Union Medical College Hospital from December 2020 to April 2021 were prospectively enrolled and divided into HIR group and DLR group according to block randomization, with 50 cases in each group. The patient′s gender, age and body mass index (BMI) were recorded. HIR group and DLR group underwent standard deviation (SD)=8.8 and SD=15 CTPA protocols in combination with HIR and DLR algorithm respectively. Other scanning parameters and contrast medium injection plan were the same. The effective dose (ED) and size-specific dose estimate (SSDE) were calculated. Regions of interest (ROIs) were drawn in the lumen of Grade 1-3 pulmonary arteries and bilateral paravertebral muscles. The corresponding CT and SD values were recorded to acquire signal to noise ratio (SNR) and contrast noise ratio (CNR). Based on a double-blind method, two radiologists evaluated the subjective noise, visualization of pulmonary arteries, and diagnostic confidence of the two groups by 5-point Likert scales. The inconsistent results were judged comprehensively by the third radiologist. Independent samples t-test was used to compare the demographic data, radiation dosage and quantitative image quality of the two groups. Mann-Whitney U test was used to compare the subjective noise, visualization of pulmonary arteries and diagnostic confidence between the two groups. Linear weighted Kappa coefficient was calculated to analyze the consistency of the qualitative scores between the two radiologists. Results:There were no significant differences in gender, age and BMI between the two groups ( P>0.05). The CT values of Grade1-3 pulmonary arteries and paravertebral muscle had no significant differences ( P>0.05). Compared with HIR group, the ED and SSDE in DLR group decreased by about 35% to 1.3 mSv and 4.20 mGy respectively, while the SNR (30±5) and CNR (26±5) of CTPA images were higher in DLR group than those in HIR group (23±5 and 20±5, with t=-6.60 and -5.90, respectively, both P<0.001). The subjective noise score was higher in DLR group than that in HIR group ( Z=-7.34, P<0.001). In addition, two radiologists showed excellent interobserver agreement in DLR group (Kappa=0.847, 95%CI 0.553-1.000). No significant differences were found in visualization of pulmonary arteries and diagnostic confidence between the two groups ( P>0.05). Conclusion:DLR further reduced the radiation dosage and improved the image quality of CTPA, with no detriment to diagnostic confidence. Thus DLR is worthy of clinical promotion.

Objective:To investigate the feasibility of chest ultra-low dose CT (ULDCT) using deep learning reconstruction (DLR) for lung cancer screening, and to compare its image quality and nodule detection rate with ULDCT iterative reconstruction (Hybrid IR) and conventional dose CT (RDCT) Hybrid IR.Methods:The patients who underwent chest CT examination for pulmonary nodules in Peking Union Medical College Hospital from October 2020 to March 2021 were prospectively included and underwent chest RDCT (120 kVp, automatic tube current), followed by ULDCT (100 kVp, 20 mA). The RDCT images were reconstructed with Hybrid IR (adaptive iterative dose reduction 3D,AIDR 3D), and ULDCT was reconstructed with AIDR3D and DLR. Radiation dose parameters and nodule numbers were recorded. Image quality was assessed using objective noise, signal-to-noise ratio (SNR) of the main trachea and left upper lobe, subjective image scores of the lung and nodules. Subjective scores were scored by 2 experienced radiologists on a Likert 5-point scale. The difference of radiation dose was compared with paired t-test between ULDCT and RDCT.The differences of quantitative indexes, objective image noise and subjective scores of the three reconstruction methods were compared with one-way analysis of variance or Friedman test. Results:Forty-five patients were enrolled, including 17 males and 28 females, aged from 32 to 74 (55±11) years. The radiation dose of ULDCT was (0.17±0.01) mSv, which was significantly lower than that of RDCT [(1.35±0.41) mSv, t=15.46, P<0.001]. There were significant differences in the image noise and SNR in the trachea and lung parenchyma and in the CT value of the trachea among ULDCT-AICE, ULDCT-AIDR 3D and RDCT-AIDR 3D images ( P<0.05). Image noise in the trachea and lung parenchyma and CT value in the trachea of ULDCT-AICE were significantly lower than those of ULDCT-AIDR 3D ( P<0.05) and comparable to RDCT-AIDR 3D ( P>0.05). There were significant differences in subjective image scores of the lung and nodules among ULDCT-AICE, ULDCT-AIDR 3D and RDCT-AIDR 3D images (χ2=50.57,117.20, P<0.001). Subjective image scores of the lung and nodules for ULDCT-AICE were significantly higher than those of ULDCT-AIDR 3D ( P<0.05), and non-inferior to RDCT-ADIR 3D ( P>0.05). All 72 clinically significant nodules detected on RDCT-ADIR 3D were also noted on ULDCT-AICE and ULDCT-AIDR 3D images. Conclusions:Chest ULDCT using DLR can significantly reduce the radiation dose, and compared with Hybrid IR, it can effectively reduce the image noise and improve SNR, and display the pulmonary nodules well. The image quality and nodule detection are not inferior to RDCT Hybrid IR routinely used in clinical practice.

Objective:To investigate the regulatory mechanism of long non-coding RNA (lncRNA) NEF on T cell immune function in postmenopausal osteoporosis (PMOP) mice.Methods:Female Balb/c mice were used to construct OVX model ( n=46) and sham control group ( n=16) . Bone marrow mesenchymal stem cells (BM-SCs) from these two groups of mice were cultured. NEF recombinant expression vector (pIRSE2-NEF) was constructed and transfected into BMSCs. RT-qPCR was used to detect NEF and miR-21 levels in BMSCs cells in sham group, OVX group, and pIRSE2-NEF group. Luciferase gene report experiment was used to verify the binding effect of NEF and miR-21. The remaining 40 OVX mice were divided into 4 groups, including OVX group ( n=10) , pIRSE2-NEF injection group (pIRSE2-NEF group, n=10) , pIRSE2-NEF combined with PD-1 inhibitor group (pIRSE2-NEF+ PD-L1-IN-1 group, n=10) , and pIRSE2-NEF combined with miR-21 mimic (mimic) group (pIRSE2-NEF+ mimic group, n=10) . The remaining 10 mice in sham group were used as the control group. ELI-SA was used to detect the levels of IFN-γ, IL-2, IL-4, IL-13 and PD-1/PD-1L in peripheral blood. Flow cytometry was used to detect the shift of serum Treg-Th17 cell subsets. Results:Compared with the Sham group (1.01±0.04, 1.00±0.03) , the expression of NEF in BMSCs of OVX group was down-regulated (0.23±0.01) , and miR-21 was up-regulated (2.96±0.05) ( P<0.05) . Compared with OVX group (1.23±0.15, 5.20±0.31) , NEF in BMSCs cells of Pirse2-nef group was significantly up-regulated (6.83±0.35) ( P<0.05) , while miR-21 was down-regulated (0.29±0.11) ( P<0.05) .NEF has a direct binding base site with miR-21.The levels of IFN-γ (3.25±0.21) , IL-2 (2.44±0.06) and Th17/Treg ratio (3.18±0.65) in peripheral blood of mice in OVX group were significantly higher than those in Sham group (1.03±0.02, 1.00±0.01, 0.86±0.09) (all P<0.05) . The levels of IL-4 (0.45±0.02) , IL-13 (0.43±0.07) , PD-1 (0.24±0.03) and PD-1L (0.51±0.06) were significantly lower than those of Sham group (1.00±0.04, 1.00±0.02, 1.00±0.03, 1.00±0.00) ( P<0.05) ; Compared with OVX, IFN-γ (2.02±0.06) , IL-2 (0.88±0.01) and Th17/Treg ratio (1.43±0.22) in Pirse2-nef group were decreased. The levels of IL-4 (0.87±0.03) , IL-13 (0.84±0.07) , PD-1 (0.79±0.06) and PD-1L (0.77±0.06) were increased (all P<0.05) ; Compared with Pirse2-nef group, IFN-γ (2.89±0.06) , IL-2 (2.07±0.07) and Th17/Treg ratio (2.39±0.38) were increased in Pirse2-nef+ PD-L1-in-1 group. The levels of IL-4 (0.68±0.03) , IL-13 (0.76±0.08) , PD-1 (0.52±0.02) and PD-1L (0.83±0.04) were decreased (all P<0.05) . Moreover, the pIRSE2-NEF+ mimic group had the same adjustment effect as the pIRSE2-NEF+ PD-L1-IN-1 group. Conclusion:lncRNA-NEF improves immune imbalance and PD-1/PD-1L-mediated Treg-Th17 cell balance in postmenopausal osteoporosis mice by sponging miR-21.

Objective: To develop medical emergency support information system for large-scale social activities based on 5G communication technology to improve efficiency of emergency medical services. Methods: The project was completed in Hangzhou, China, from March 2016 to September 2019. Based on the medical service of large social activities, five information terminals are constructed, including on-site mobile terminal, on-board first aid terminal, expert remote consultation terminal, hospital terminal, and command dispatch center. The system can realize the real-time communication of medical information, patient's vital signs, audio, picture and video information, and can also make intelligent scheduling decisions for patients. Results: 5G Emergency Medical information System for Large-scale Social Activities has been completed, which consists of three parts: command and control platform, on-site rescue platform, and evacuation support platform. The command and monitoring platform displays the information of on-site medical teams, ambulances, hospitals and experts through web pages, and realizes multi-party video communication at any time, as well as text, voice and image information of patients' current condition, so as to realize command, dispatch and display statistical summary information. On-site rescue terminal includes patient information input, video signal acquisition and physiological information acquisition equipment. It realizes multiple methods of patient information input, vital signs and physiological information acquisition, multi-angle video acquisition and transmission to the command center. The evacuation support platform includes vehicle emergency terminal, remote expert consultation terminal, hospital terminal and UAV system. Vehicle terminal can scan and transfer with on-site ambulance team, record physiological information during transit, and also acquire and transmit monitor, electrocardiogram and ultrasound information. Hospital terminals can obtain patient information at the first time and prepare for first-aid in hospital. The remote expert terminal can be dispatched by the command center and the hospital terminal, and can join the remote consultation at any time. Unmanned aerial vehicle (UAV) system can transfer medical material between any locations. Conclusions This system can guarantee the patients to be transported from the scene to the ambulance and finally to the hospital during the large-scale social activities. In the whole process, the information transmission and dispatching decision-making are initially realized, and the statistical report forms can be made. However, to fully exert its advantages, it still needs the support of the complete 5G network and continuous optimization in real scenarios.