Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Objective:To investigate the mechanism of trigger point deactivation induced by pressing manipulation in a rat model and to explore its potential regulation of the inflammatory response through the extracellular signal-regulated kinase(ERK)/nuclear factor-κB(NF-κB)pathway. Methods:Fifty male Sprague-Dawley rats were randomly divided into a blank group,a model group,a pressing manipulation group,an ERK agonist group,and a pressing manipulation+ERK agonist group,with 10 rats in each group.Except for the blank group,rats in other groups were used to establish the trigger point rat model using the blunt blow combined with the eccentric exercise method.The pressing manipulation group underwent pressing manipulation intervention at the trigger points.The ERK agonist group received an injection of recombinant human epidermal growth factor via the tail vein.The pressing manipulation+ERK agonist group received interventions from both the pressing manipulation and ERK agonist groups.The pressure pain threshold(PPT)was measured by a mechanical pain threshold detector before and after the intervention.The histological changes were evaluated by hematoxylin-eosin staining after the intervention;the expression levels of ERK,phosphorylated ERK(p-ERK),NF-κB p65(p65),phosphorylated NF-κB p65(p-p65),and phosphorylated NF-κB inhibitor(p-IκB)were detected by Western blotting;the levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay. Results:The PPT increased(P<0.05);the inflammatory cells disappeared;the ratios of p-ERK/ERK,p-p65/p65,and p-IκB/β-actin,also the levels of IL-1β,IL-6,and TNF-α all decreased in the pressing manipulation group after the intervention compared with the model group(P<0.05).The PPT decreased significantly(P<0.05),the inflammatory cell presence increased,and the ratios of p-ERK/ERK and p-p65/p65 were elevated(P<0.05);additionally,the levels of IL-6 and TNF-α were significantly higher in the pressing manipulation+ERK agonist group compared with the pressing manipulation group(P<0.05).The PPT was significantly lower(P<0.05),the inflammatory cell count was higher,the ratios of p-ERK/ERK and p-IκB/β-actin and the levels of IL-1β and TNF-α were significantly higher in the ERK agonist group compared with the pressing manipulation+ERK agonist group(P<0.05). Conclusion:Pressing manipulation can effectively alleviate inflammation and pain in trigger point model rats,potentially by inhibiting the ERK/NF-κB signaling pathway.

Objective:To evaluate the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative cellular immune function in the patients undergoing posterior spinal internal fixation.Methods:Ninety patients, aged 40-70 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective posterior spinal internal fixation in our hospital, were divided into 2 groups ( n=45 each) using a computer-generated table of random numbers: routine group and experiment group.Total intravenous anesthesia was used in routine group, while total intravenous anesthesia combined with TEAS was applied in experiment group.In experiment group, bilateral Zusanli and Sanyinjiao acupoints were stimulated with 2/15 Hz disperse-dense waves at the intensity that could be tolerated by patients at 30 min before induction of anesthesia, maintaining with 2/100 Hz disperse-dense waves from the end of induction until the end of operation at the same stimulation intensity before induction.Bilateral Neiguan and Taichong acupoints were stimulated for 30 min each time with 2/15Hz disperse-dense waves once a day at 1st-4th days after operation.In routine group, the electrodes were connected at the same time period, but no stimulation was given.Venous blood samples were collected before induction of anesthesia, at 1 h after surgery, and on 1st, 3rd, and 5th days after surgery, and the percentage of CD3 + , CD4 + , CD8 + T lymphocytes, CD4 + /CD8 + ratio, WBC count and percentage of neutrophils (NE%) were determined by flow cytometry, and the consumption of intraoperative anesthetics, use of postoperative analgesics, nausea and vomiting, dizziness, infection and length of hospital stay were recorded. Results:Compared with routine group, the total consumption and consumption index of remifentanil were significantly decreased, the percentage of CD3 + T lymphocytes was increased on 3rd and 5th postoperative days, the NE% was decreased on 1st postoperative day, and the incidence of dizziness was decreased ( P<0.05), and no significant change was found in the other indicators in experiment group ( P>0.05). Conclusions:Perioperative TEAS can improve postoperative cellular immune function and has a certain potential value in preventing postoperative infection in the patients undergoing posterior spinal internal fixation.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To investigate the expression pattern of TCR variable region subfamily (Vβ and Vδ) in patients with mature T-cell lymphoma (TCL), and to compare the diagnostic value of TCRVβ and TCRVδ analysis in TCL.Methods:The TCRVβ flow cytometry kit was used to detect the expression of Vβ subtypes of αβT cell in 199 patients with αβ TCL and 398 patients with non-TCL, who hospitalized in Jiangsu Provincial People Hospital from 2011 to 2020. Among them, 185 cases of αβ TCL and 355 cases of non-TCL also underwent TCRβ and TCRγ gene rearrangement detection. The TCRVδ based 10-color protocol was used to detect the expression of Vδ subtypes in 24 cases of γδTCL, 10 cases of normal controls, and 15 cases with reactively higher CD4 and CD8 double-negative ratio from 2017 to 2020, and 24 cases of γδTCL and 15 cases with reactively higher CD4 and CD8 double-negative ratio underwent TCRβ, TCRγ and TCRδ gene rearrangement detection. The diagnostic performance and degree of coincidence for detecting malignant clonality were compared between TCRVβ and TCRVδ analysis and the TCR gene scanning method.Results:In the 199 cases of αβ TCL, 182 cases (91.5%) showed restricted expression or the sum of the positive percentages of the subgroups was less than 30% for the 24 TCRVβ subtypes. Among them, the subfamily members with the highest incidence of clonal T lymphocytes were TCRVβ13.2 (12.6%, 23/182) and TCRVβ3 (8.2%,15/182); the TCRVβ subtypes showed nonclonal results in 99.0% (394/398) of non-TCL. All 24 cases of γδTCL (100%) showed abnormal distribution patterns of Vδ1 and Vδ2, of which 19 cases showed restricted expression of Vδ1, and the remaining 5 cases had negative expression of either Vδ1 or Vδ2, and the positive rate of Vδ1 cells was significantly higher than that of Vδ2 cells (79.9%±10.8% vs 0.7%±0.3%, P<0.001). Among the normal control and cases with reactively higher CD4 and CD8 double-negative ratio, the positive rate of Vδ2 cells was significantly higher than that of Vδ1 cells (73.7%±6.7% vs 15.6%±4.2%, P<0.001), and all cases (25/25) showed a normal distribution pattern. In terms of the diagnostic performance of TCL, there was no significant difference of sensitivity and specificity between TCR variable region subfamily detection by flow cytometry and TCR gene scanning technology (the sensitivity was 92.4% and 91.4% respectively; the specificity was 99.0% and 95.9% respectively, P=0.065), and the coincidence rate of the two diagnostic methods is high (Kappa=0.809, P<0.001). Conclusion:Detection of TCR variable region subfamily by flow cytometry could quickly and effectively diagnose mature TCL.

Objective: To evaluate the diagnostic value of bronchoalveolar lavage (BAL) for pulmonary complications in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its safety. Methods: Patients with pulmonary complications after allo-HSCT underwent BAL. Microbiological smears, culture, PCR of CMV-DNA, EBV-DNA and TB-DNA, macro genomes new generation sequencing (mNGS) techniques were performed to detect pathogens in BAL fluid (BALF) . Results: A total of 73 allo-HSCT patients with 86 times of pulmonary complications enrolled this prospective study. They underwent 132 times of BAL procedures. The clinical diagnoses of 88.4% cases were made based on BALF analysis. Of them, 67 cases (77.9%) had infectious pulmonary complications, including 29 cases (33.7%) of fungal infection, 18 cases (20.9%) of mixed infection, 11 cases (12.8%) of viral infection and 9 cases (10.5%) of bacterial infection. The other 9 cases (10.5%) of non-infectious pulmonary complications included 8 cases (9.3%) of idiopathic pneumonia syndrome (IPS) and 1 case (1.2%) of pulmonary infiltration of lymphoma. The diagnoses of the remaining 10 cases (11.6%) were not determined. The platelet counts of 33 patients were less than 50×10⁹/L before BAL. None of them developed severe bleeding complications during or after BAL. Transient fever occurred in 10 patients after BAL. Blood cultures showed staphylococcal bacteremia in them and anti-infection therapies were effective. No life-threatening complications occurred in all of the patients during or after BAL. Conclusion BALF analysis was informative for the diagnosis of pulmonary complication and safe for patients with pulmonary complications after allo-HSCT.

Objective To summarize the clinical features and genetic diagnosis of Kabuki syndrome. Methods The clinical data of Kabuki syndrome in 2 children were retrospectively analyzed. Results Both of them were male and over 1 year old. They had special facial features and febrile convulsion. Gene detection indicated that both of them had mutation in KMT2D (or MLL2) gene, but the clinical phenotypes were different. Conclusion Children with clinically suspected Kabuki syndrome can be confirmed by gene detection.

Objective To investigate the effect of the humanized care on the blood glucose, blood lipid and diabetic ketoacidosis control of type 1 diabetes patients outside the hospital. Methods Fifty type 1 diabetes patients were enrolled in this study, aged from 18 to 30 years old, outside the hospital. The duration of this study was from Mar 2009 to Jan 2016.The clinical and laboratory data of patients,including HbA1c,LDL-C,HDL-C,TG and diabetic ketoacidosis were collected and analyzed. Results About 60.0% and 80.0% of type 1 diabetes pa-tients achieved the goals of contorlling glycemia (HbA1c < 6.5%) and dyslipidemia (LDL-C < 2.6 mmol/L) respec-tively, after receiving the humanized care outside the hospital, while only 32.0% and 22.0% of type 1 diabetes pa-tients achieved these goals before.Moreover,after receiving the humanized care outside the hospital,only 16.0% of type 1 diabetes patients suffered from diabetic ketoacidosis which was 40.0% before.Conclusions The humanized care outside the hospital can help patients to acheive the goals of contorlling glycemia and dyslipidemia among the type 1 diabetes.Besides,it contributes to reduce the incidence rate of the diabetic ketoacidosis.

Objective To evaluate the efficacy of peripheral blood combined with cord blood model for haplo-hematopoietic stem cell transplantation and the occurrence,survival of complications in patients of different ages.Methods From January 2014 to December 31,2017,there were 50 patients undergoing haploid allogeneic hematopoietic stem cell transplantation in our department.There were 39 males and 11 females.The median age was 35 (9-67) years.The stratification was divided into 3 groups.In group A,17 patients were younger than 30 years old;in group B,19 patients were between 30 and 49 years old,and in group C,14 patients were not less than 50 years.No remission was assessed before transplantation in this group.On the morning of the reinfusion,the selection of a third-party umbilical cord blood for transfusion reduced the occurrence of GVHD.Peripheral blood was infusion in the afternoor.All patients were treated with ATG + CSA + shortterm MTX to prevent GVHD.Results Two patients died of infection prior to graft,4 (8.0％) patients were graft failure.The median time of ANC≥0.5 × 109/L (range) and platelet ≥20 × 109/L (range) in the other patients were 14d(10-22 d) and 20(11-186) d,individually.The median time of full donor chimerism(range)was 28d(14-42 d).Graft failure was occurred in one case (5.9％),two cases (10.5％) and one case (7.1％) in each group,with no statistically significant difference (x2 =0.282,P =0.868).With a median follow-up of 7.2 months (0.4-27.2 months),12 (24％) had aGVHD of Ⅱ-Ⅳ degrees,among them,6 cases (35.3％) in group A,5 cases (26.3％) in group B,1 case (7.1％) in group C had aGVHD of Ⅱ-Ⅳ degrees.There was no significant in the incidence of aGVHD in three groups (x2 =3.624,P =0.180).Twenty-nine (58％) patients had viral infections after transplantation.One patient in both group A and B relapsed,and there was no recurrence in group C.21 (42％) patients died and 29 (58％) patients survived.The predicted 2-year overall survival (OS) was 60.2％.In group C,the 2-year overall survival (OS) was 77.1％.Conclusion The haploidentical hematopoietic cell transplantation model of peripheral blood combined with third-party umbilical cord blood transfusion has a good outcome and prolonged survival time in high-risk elder patients.The use of suitable conditioning regimens did not increase the incidence of aGVHD and virus infection.