Objective:To investigate the values of two-dimensional and three-dimensional echocardiographic parameters in predicting pulmonary vascular resistance (PVR) in chronic pulmonary thromboembolic pulmonary hypertension (CTEPH).Methods:A total of 141 patients diagnosed with CTEPH in China-Japan Friendship Hospital from November 2015 to December 2022 were included. Two-dimensional echocardiographic indicators reflecting PVR were constructed according to the calculation formula of PVR: echocardiographic estimated systolic pulmonary artery pressure (sPAP Echo)/left ventricular end-diastolic diameter (LVIDd), echocardiographic estimated mean pulmonary artery pressure (mPAP Echo)/LVIDd. sPAP Echo/left ventricular end-diastolic volume (LVEDV), sPAP Echo/left ventricular cardiac output (LVCO) were measured by three-dimensional echocardiography. The correlations between two-dimensional and three-dimensional echocardiographic ratios and invasive PVR were then analyzed using the Spearman correlation method. Using receiver operating characteristic curve analysis, cut-off values for the ratios were generated to identify patients with PVR>1 000 dyn·s -1·cm -5. Pre- and postoperative hemodynamics and echocardiographic data were analyzed, as well as the correlation between the reduction rate of the echocardiographic index and PVR in 54 patients who underwent pulmonary endarterectomy (PEA). Results:sPAP Echo/LVIDd, sPAP Echo/LVEDV and sPAP Echo/LVCO were moderately correlated with PVR( rs=0.62, 0.52, 0.63, both P<0.001). The ratio of sPAP Echo to LVEDV, when greater than or equal to 1.41, had a sensitivity of 0.800 and a specificity of 0.930 for determining PVR >1 000 dyn·s -1·cm -5 (AUC=0.860, P<0.001). Similarly, the ratio of sPAP Echo to LVIDd, when greater than or equal to 2.14, had a sensitivity of 0.647 and a specificity of 0.861 for determining PVR >1000 dyn·s -1·cm -5 (AUC=0.830, P<0.001). The sPAP Echo/LVIDd and mPAP Echo/LVIDd significantly decreased after PEA (both P<0.001). The sPAP Echo/LVIDd and mPAP Echo/LVIDd reduction rate (ΔsPAP Echo/LVIDd and ΔmPAP Echo/LVIDd) were significantly correlated with PVR reduction rate (ΔPVR), respectively ( rs=0.61, 0.63, both P<0.05). Conclusions:Two-dimensional ratio sPAP Echo/LVIDd and three-dimensional ratio sPAP Echo/LVEDV can be used to noninvasively estimate PVR in CTEPH patients. The conventional ratio sPAP Echo/LVIDd is convenient and reproducibly suitable for monitoring the improvement of PVR before and after treatment, and its ratio of 2.14 can predict the significant increase of PVR in CTEPH patients (>1 000 dyn·s -1·cm -5).

Objective:To investigate the safety and efficacy of balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension (PH) of chronic thromboembolic pulmonary hypertension(CTEPH) after pulmonary endarterectomy (PEA).Methods:Patients diagnosed as PH after PEA in China-Japan Friendship Hospital from Oct 2016 to Jun 2022 were included. The indication for BPA was decided on the basis of a consensus of the multi-disciplinary team for all patients with CTEPH. Before treatment, the patient′s exercise tolerance and pulmonary artery flow parameters were evaluated. A comparative analysis of various parameters before BPA treatment and at the last BPA was conducted. 6-min walk distance (6MWD) was analyzed using the paired Wilcoxon test; N-terminal pro-brain natriuretic peptide (NT-proBNP), mixed venous oxygen saturation, mean pulmonary arterial pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were compared using the paired-samples t-test. WHO functional class was compared using McNemar′s test. Results:Twenty patients with a total of 130 vessels underwent 46 sessions of BPA treatment. The postoperative 6-minute walk distance (6MWD) [447 (415, 485) m] showed a significant improvement compared to the preoperative baseline [389 (335, 470) m] ( Z=6.52, P<0.05), Postoperative mixed venous oxygen saturation (72.0%±1.9%) showed a significant improvement compared to the preoperative levels (64.0%±2.7%) ( t=2.14, P<0.05).Postoperatively, plasma NT-proBNP [(351.9±129.9) pg/ml], mPAP [(24.2±1.9) mmHg], and PVR [(3.0±1.4) WU] significantly decreased compared to preoperative levels [(982.5±426.2) pg/ml, (33±2.1) mmHg, (8.0±1.6) WU)] ( t=3.38, 1.22, 2.10, P<0.05 for all). Postoperatively, there was a significant improvement in WHO functional class (Ⅰ，Ⅱ，Ⅲ，Ⅳ: 14, 4, 2, 0 cases) compared to preoperative status (Ⅰ，Ⅱ，Ⅲ，Ⅳ: 0, 13, 5, 2 cases) ( χ2=20.17, P<0.05). Four cases of pulmonary artery dissection and one episode of hemoptysis occurred postoperatively, with no other complications reported. Conclusions:BPA can significantly improve exercise tolerance and hemodynamic parameters for residual PH after PEA. BPA is a relatively safe and effective treatment for residual PH after PEA.

Objective:To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats.Methods:Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg -1·min -1 and remifentanil 1.0 μg·kg -1·min -1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T 0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R ( P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated ( P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z ( P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups ( P>0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.

Objective To explore the effects of different phenotypes macrophages(Mφs)on the proliferation,mi-gration and osteogenic differentiation of periodontal ligament stem cells(PDLSCs).Methods PDLSCs were isola-ted and cultured by tissue block method.Tohoku Hospital Pediatrics-1(THP-1)cell line was stimulated to activate into unpolarized Mφs(M0),then induced to polarize into type Ⅰ Mφs(M1)and type Ⅱ Mφs(M2).Quantitative real-time PCR(qPCR)detected the inflammatory factors tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,IL-6,IL-10 and transforming growth factor-β(TGF-β)mRNA expression level.After collecting culture superna-tants with different phenotypes,PDLSCs were stimulated,native control(NC)group did not receive the culture su-pernatant of Mφs.The effects of PDLSCs proliferation were assessed via Methylthiazolyldiphenyl-tetrazolium bro-mide(MTT)assay,while scratch assays were employed to evaluate their migration.Western blot was utilized to analyze the protein expression of Runt-related transcription factor 2(RUNX2)and alkaline phosphatase(ALP).Additionally,Alizarin Red staining was performed to investigate the deposition of calcified nodules in PDLSCs.Re-sults qPCR showed the relative expression of TNF-α,IL-1 β and IL-6 in M1 Mφs were higher than those in M0 and M2 Mφs(P＜0.05),and the relative expression of IL-10 and TGF-β in M2 Mφs were higher than those in M0 and M1 Mφs(P＜0.05);Western blot showed the expression of RUNX2 and ALP proteins in PDLSCs in M0 and M2 groups was higher than those in the NC group(P＜0.05),Alizarin Red staining showed increased calcified nodule deposition in PDLSCs in M0,M1 and M2 groups compared to the NC group;MTT assay showed the prolifer-ation of PDLSCs in the M0 and M1 groups was suppressed compared to the NC group(P＜0.05);and scratch ex-periment showed the migratory capacity of PDLSCs in the M1 and M2 groups was stronger than that in the NC group.Conclusion M0 and M1 Mφs inhibit PDLSCs proliferation,M1 and M2 Mφs promote PDLSCs migration,and all types of Mφs promote osteogenic differentiation of PDLSCs.

Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.

Objective To investigate the value of intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)in quantitatively evaluating the involved muscle in idiopathic inflammatory myopathies(IIM).Methods Totally,50 patients with clinically diagnosed IIM(IIM group)and 15 healthy controls(control group)were selected for bilateral thigh MRI examination,including IVIM-DWI sequences.The right quadriceps(vastus lateralis,vastus intermedius,vastus medialis,and rectus femoris)of all subjects were selected as region of interest(ROI).Single-exponential and double-exponential analysis were employed to quantitatively measure IVIM-DWI parameters,including apparent diffusion coefficient(ADC),D,f,and D*.Based on T1WI and T2WI fat-suppressed images of the right quadriceps,these muscles were divided into affected and unaffected groups.One-way analysis of variance was used to compare IVIM-DWI parameters between affected group,unaffected group,and control group.Receiver operating characteristic(ROC)curve was performed to analyze the differences in IVIM-DWI parameters among the above groups.Results The D and ADC values were significantly higher in the affected group compared to the unaffected group and the control group(P＜0.001).ROC curve analysis revealed that D and ADC values had moderate diagnostic significance with area under the curve(AUC)of 0.794 and 0.882,respec-tively.The cutoff values for D values and ADC values were 1.63×10-3 mm2/s and 1.44×10-3 mm2/s,respectively.Additionally,MRI follow-up performed one year after treatment in three patients with IIM showed significant resolution of inflammatory edema in thigh muscles,accompanied by a marked decrease in IVIM-DWI parameter values,particularly D values and ADC values.Conclusion The affected muscle in IIM show distinctive diffusion characteristics,and IVIM-DWI parameters,especially D values and ADC val-ues,show a higher diagnostic value for assessing muscle status in IIM.In addition,IVIM-DWI parameters also demonstrate a promis-ing value in the follow-up of IIM,which requires further confirmation in larger cohorts.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To evaluate the clinical efficacy of single-wide-tunnel endoscopic submucosal dissection with single-clip-line traction (W-ESTD) for the treatment of early esophageal cancer and precancerous lesions with large area (≥ 3/4 circumference).Methods:A retrospective analysis was performed on patient data of large early esophageal cancer or precancerous lesions treated with digestive endoscopy at the Affiliated Huai'an NO.1 People's Hospital of Nanjing Medical University from January 2018 to January 2023. Patients were divided into W-ESTD group and endoscopic submucosal double-tunnel dissection (D-ESTD) group based on the technique used. Surgical speed, en bloc resection rate, R0 resection rate, curative resection rate, intraoperative and postoperative complications were compared between the two groups.Results:A total of 44 patients with large early esophageal cancer or precancerous lesions were included in this study, including 23 cases in the W-ESTD group and 21 cases in the D-ESTD group. There was no statistically significant difference in baseline data between the two groups ( P>0.05). The operating speeds of W-ESTD and D-ESTD groups were 29.97±11.89 mm2/min and 22.65±6.30 mm2/min, respectively, with significant difference ( t=2.580, P=0.014). There was no statistically significant difference between the two groups in terms of en bloc resection rate [95.7% (22/23) VS 100.0% (21/21), P=1.000], R0 resection rate [87.0% (20/23) VS 90.5% (19/21), P=1.000], or curative resection rate [73.9% (17/23) VS 85.7% (18/21), P=0.462]. No recurrence occurred. Intraoperative muscular injury occurred in 3 cases in the W-ESTD group and 5 cases in the D-ESTD group, and postoperative esophageal stricture occurred in 11 cases and 8 cases respectively, with no significant differences between the two groups ( P>0.05). Conclusion:Compared to D-ESTD, W-ESTD can significantly improve surgical speed and demonstrate itself as a safe and effective approach for treating large early esophageal cancer and precancerous lesions.

Objective:To analyze the curative effect of sandwich cheiloplasty for the treatment of macrocheilia secondary to port-wine stain (PWS).Methods:A total of 43 patients, including 20 males and 23 females, aged 37.0 years (ranged from 4 to 69 years), who underwent sandwich cheiloplasty for the treatment of macrocheilia secondary to PWS from March 2008 to March 2022 were retrospectively enrolled. According to the location of the lesions, they were divided into two groups: upper lip group (21 cases) and lower lip group (22 cases). Pathological examinations were performed in all excised specimens. Postoperative attentions should be paid to keeping incisions locally clean, observing the blood supplying, and taking care of fluid accumulation or incision split. After discharge, the lip appearance and function were evaluated every six months in the outpatient department, and the long-term efficacy was further divided into three levels: grade Ⅰ (poor), grade Ⅱ (moderate), and grade Ⅲ (good). The comparison of grade data named long-term efficacy between the two groups was conducted by Mann-Whitney U test.Results:All 43 patients underwent sandwich cheiloplasty, of which 40 patients received one operation, whereas the other 3 received two due to recurrences. One-stage incision healing was achieved in 43 cases, whereas partial mucosal necrosis appeared in 2 cases, and slight incision dehiscence occurred in 1 case, which healed well after local dressing change. The pathological examination results of 43 excised tissue specimens all showed capillary malformations. After follow-up for 1 to 10 years, long-term efficacy evaluation was made up as follows: 36 cases were evaluated as grade Ⅲ, 7 cases as grade Ⅱ, and 0 case as grade Ⅰ. There were 18 cases of grade Ⅲ, and 3 cases of grade Ⅱ in group A, compared to 18 cases of grade Ⅲ, and 4 cases of grade Ⅱ in group B. By rank sum test, there was no significant difference in overal efficacy between the two groups ( Z=0.342, P>0.05). Conclusions:Sandwich cheiloplasty for the treatment of macrocheilia secondary to PWS effectively removes malformed vascular lesions, and consequently, it can achieve a good long-term therapeutic effect.