Evidence for causal effects of neuropsychiatric conditions on risk for Venous Thromboembolism: a univariable and multivariable Mendelian randomization study.

BACKGROUND: Substantial observational evidence suggests an association between neuropsychiatric conditions and Venous Thromboembolism (VTE). However, the causal relationship between these two conditions requires further investigation. Therefore, we employed a two-sample Mendelian Randomization (MR) approach to assess bidirectional causal effects between four neuropsychiatric conditions and VTE, Deep Vein Thrombosis (DVT), and Pulmonary Embolism (PE). METHODS: Genetic variants associated with four neuropsychiatric conditions, including Schizophrenia (SCH), Major Depressive Disorder (MDD), Bipolar Disorder (BD), and Epilepsy, as well as VTE, DVT, and PE were selected. Bidirectional univariable and multivariable MR methods were applied to evaluate causal relationships among these conditions. The primary causal estimates were obtained using the Inverse Variance Weighted (IVW) method with multiplicative random effects, supplemented by MR Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analysis was conducted using MR pleiotropy residual sum ,funnel plots and outlier (MR-PRESSO) method. RESULTS: Univariable MR results showed that genetic susceptibility to MDD increases the risk of VTE and PE (VTE: OR=1.25, 95%CI: 1.08-1.46, P=0.004; PE: OR=1.36, 95%CI: 1.09-1.69, P=0.006), and PE has an adverse causal effect on MDD (OR=1.02, 95%CI: 1.00-1.04, P=0.026). Adjustment for confounders such as obesity, sleep duration, smoking, physical activity, and alcohol consumption revealed that increased genetic susceptibility to MDD is also associated with VTE and PE. CONCLUSION: Our study suggests that genetic susceptibility to MDD may have an adverse causal effect on the risk of VTE and PE, and PE has a reverse causal effect on MDD. Prevention and early diagnosis of depression are crucial in the management of VTE and PE.

[Comparison of efficacy between personalized vestibular rehabilitation and otolith reposition for the treatment of atypical benign paroxysmal positional vertigo].

Objective: To compare the clinical efficacy of personalized vestibular rehabilitation and otolith reposition in treating atypical benign paroxysmal positional vertigo (BPPV). Methods: A randomized controlled trial was carried out. Fifty patients diagnosed with atypical BPPV in the Vertigo Clinic of the First Affiliated Hospital of Shandong First Medical University from October 2022 to September 2023 were recruited and randomly divided into manual reduction group (25 cases) and vestibular rehabilitation group (25 cases) according to the random number table. All patients were given flunarizine. Patients in the manual reduction group were treated by Epley maneuver and (or) Barbecue maneuver, while the vestibular rehabilitation group was given personalized vestibular rehabilitation therapy. After two weeks' treatment, the clinical symptoms (positional vertigo/nystagmus) and total dizziness handicap inventory (DHI) score, DHI physical (DHI-P), DHI emotional (DHI-E), and DHI functional (DHI-F) of the two groups were evaluated and compared. Results: A total of 50 patients diagnosed with atypical BPPV were included, including 23 males and 27 females, with an average age of (48.8±14.5) years. There was no statistically significant difference between the two groups in age, gender, disease severity, Romberg, position test abnormality ratio (Dix-hallpike/Roll test), temperature test, and video head impulse test baseline test results (all P>0.05). After 2 weeks of treatment, the effective rates of the treatment in the manual reduction and vestibular rehabilitation groups were 56.0% (14/25) and 88.0% (22/25), respectively, with a statistically significant difference (P=0.025). The total DHI score, DHI-P, DHI-E, and DHI-F scores in both groups were significantly decreased after treatment (all P<0.001). Compared with the manual reduction group, the total DHI score (23.2±2.7 vs 36.4±15.7, P=0.002), DHI-P (10.2±4.6 vs 13.7±5.3, P=0.016) and DHI-F (6.5±6.4 vs 13.0±7.2, P=0.002) in the vestibular group were lower, however, there was no significant difference in DHI-E score between the two groups (6.6±4.8 vs 9.6±7.3, P=0.087). Conclusion: Compared with otolith reposition, personalized vestibular rehabilitation therapy plays a better role in improving the symptoms and decreasing DHI score for patients with atypical BPPV.

[Study on the fit testing for the workers wearing hearing protection device in machinery manufacturing enterprises].

Objective: To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing. Methods: From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed. Results: The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [M (Q(1), Q(3)) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant (P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups (P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion: The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

[Construction of a risk prediction model for diabetes after kidney transplantation based on genome-wide association study].

Objective: To explore the clinical risk factors and susceptibility genes of diabetes after kidney transplantation (PTDM) and construct a risk prediction model for PTDM. Methods: The data of kidney transplant recipients who underwent follow-up in the Affiliated Lihuili Hospital, Ningbo University and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2001 to December 2022 were retrospectively analyzed. The recipients were divided into PTDM group and Non-PTDM group according to whether they were complicated with PTDM. The differences in clinical indicators between the two groups were compared, the risk factors affecting the incidence of PTDM were determined, and susceptibility genes of PTDM were screened by genome-wide association study (GWAS). PTDM risk prediction models based only on clinical indicators (Model 1) and clinical indicators combined with susceptibility genes (Model 2) were established respectively, and the predictive performance of the two prediction models was compared. Finally, the Nomogram of the optimal model was drawn, and the discrimination, calibration and clinical applicability of the model were evaluated. Results: A total of 113 kidney transplant recipients (70 males and 43 females) were included, with an average age of (46.2±10.8) years. There were 51 cases in PTDM group and 62 cases in Non-PTDM group. The related factors screened by GWAS and logistic regression analysis included family history of diabetes (OR=88.912, 95%CI: 5.827-1 356.601, P=0.001), preoperative triglyceride (TG) (OR=1.888, 95 %CI: 1.150-3.098, P=0.012), uric acid (UA) (OR=1.011, 95%CI: 1.000-1.022, P=0.045) and rs802707 (OR=10.046, 95%CI: 1.462-69.042, P=0.019). The area under the curve (AUC) of the receiver operating characteristics analysis (ROC) predicted by Model 1 for PTDM was 0.891 (95%CI: 0.811-0.972), with the sensitivity of 0.889 and the specificity of 0.742. The AUC of ROC curve predicted by Model 2 for PTDM was 0.930 (95%CI: 0.864-0.995), with the sensitivity of 0.885 and the specificity of 0.900. Conclusions: Family history of diabetes, preoperative TG and UA, and rs802707 are significantly associated with the occurrence of PTDM. In addition, the combination of susceptibility genes could improve the predictive ability of clinical indicators for the risk of PTDM.

[Short term clinical observation of keratoconus treated with stromal lenticule addition keratoplasty combined with corneal collagen cross-linking].

Objective: To investigate the efficacy of Femtosecond laser-assisted stromal lenticule addition keratoplasty (SLAK) combined with corneal collagen cross-linking (CXL) in the treatment of middle and advanced Keratoconus. Methods: It was a retrospective case series study. Data of 23 cases (24 eyes) of keratoconus treated with femtosecond laser-assisted SLAK combined with CXL in Laser Vision Centre of Xi'an No.1 Hospital from September 2020 to June 2022 were collected, including 16 males and 7 females, aged (23.69±5.18) years. The thickness, diopter number and diameter of the donor corneal stromal lens were assessed. uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and diopter were recorded before and 1, 3, and 6 months after surgery. Sirius 3D fault corneal topography instrument to measure flat simulated keratometry (Kf), steep simulated keratometry (Ks) and the difference between them (ΔK), as well as central corneal thickness (CCT) and corneal high-order aberration. Results: Six months after surgery, CCT (454.83±50.01) µm were significantly higher than before (384.92±35.45) µm (P<0.05). Six months after surgery, UCVA (1.41±0.32) was significantly lower than before (1.11±0.33)(P<0.05). Six months after surgery, spherical diopter [(-15.73±7.89) D], Kf [(56.82±4.76) D] and Ks [(61.00±4.70) D] were significantly higher than before [(-12.08±5.99) D, (53.55±4.95) D, (58.65±5.10) D] (P<0.05). There was no significant difference in BCVA, column mirror degree and higher order aberrations before and 6 months after surgery(P>0.05). No corneal stromal lens folds, melting and displacement were observed in all eyes during the follow-up period, and no corneal opacity or immune rejection was observed. Conclusions: femtosecond laser-assisted SLAK combined with CXL can significantly increase the corneal thickness of keratoconus and has good effectiveness. In addition, six months of postoperative follow-up of patients showed no significant changes in BCVA and high-order aberrations in the 6 mm central diameter of the cornea, and no postoperative adverse reaction were found in all eyes, indicating that the operation has certain safety.

[Clinical characteristics of primary hemophagocytic lymphohistiocytosis associated with perforin gene deficiency: a single-center retrospective study].

Objective: This study aimed to investigate the clinical characteristics of patients diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH) associated with perforin gene deficiency. Methods: We retrospectively analyzed the clinical data of 16 pHLH patients associated with perforin gene deficiency at Beijing Friendship Hospital, Capital Medical University, from April 2014 to August 2021. The mutation sites, mutation types, family history, clinical characteristics, and prognosis of the patients were assessed. Results: A total of 16 patients, including ten males and six females, with a median onset age of 17.5 years (range: 4-42 years), were enrolled in this study. Sixteen different mutations were identified, consisting of 11 missense mutations, one nonsense mutation, two frameshift mutations, and two in-frame mutations. All patients harbored at least one deleterious missense mutation, with the most common mutation sites being c.1349C>T (p.T450M) and c.503G>A (p.S168N). Decreased natural killer (NK) cell activity was observed in 11 patients, reduced perforin protein expression in ten patients, concurrent Epstein-Barr virus (EBV) infection at onset in eight patients, a family history in two patients, and central nervous system involvement in four patients. Eleven cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), with eight cases surviving. The median survival time of non-transplanted patients was eight months (range: 4-18 months), while that of transplanted patients was reported as "not reached". Conclusions: Emphasizing the diagnosis of pHLH in adults with perforin gene deficiency. In addition, it should be noted that EBV infection can potentially act as a triggering factor in such disease, and allo-HSCT exerts a substantial effect on the prognosis of patients.

Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy.

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

[Recommendations for the diagnosis and treatment of rheumatic diseases-related hemophagocytic syndrome in China].

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians' understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.

[Application of the two-step sentinel lymph node biopsy with double-tracer in early staged endometrial cancer].

Objective: To explore the feasibility and clinical value of sentinel lymph node (SLN) biopsy through cervix-uterine combined two-step injection with two tracers in patients with early stage endometrial cancer. Methods: From July 2019 to April 2021, a total of 73 patients, aged (54.2±3.3) year, who were preoperatively diagnosed as stage Ⅰ-Ⅱ endometrial cancer (including 56 low-risk patients and 17 medium-high risk patients) in Affiliated Hospital of Qingdao University were selected. According to the different sites of tracer injection, the patients were randomly divided into three groups: cervical injection group (25 cases): 1 ml of nano-carbon was used to inject at 3 and 9 o'clock in the cervix; uterine injection group (21 cases): the magnetic resonance imaging examination was performed to determine the location of the lesion, and 4 ml of methylene blue was injected into the uterine body at 2 sites where the lesion was located; combined injection group (27 cases): cervical injection of nano-carbon (1 ml) combined with uterine injection of methylene blue (4 ml). The SLN in all patients were identified under laparoscopy, removed, and followed by frozen pathological examination. Pathological ultra-staging was performed if the postoperative pathological outcome of SLN was negative. The total detection rate of SLN, bilateral pelvic SLN detection rate, sensitivity, negative predictive value, and location of SLN in each group were calculated and compared. Results: (1) In 73 patients with endometrial cancer, the overall detection rate of SLN was 88% (64/73), the detection rate of bilateral pelvic SLN was 67% (49/73), and the detection rate of para-aortic SLN was 49% (36/73). The overall detection rate of SLN (71%, 15/21) and bilateral pelvic SLN (43%, 9/21) in the intrauterine injection group were significantly lower than those in the cervical injection group [92% (23/25), 76% (19/25), respectively] and the combined injection group [96% (26/27), 78% (21/27), respectively; all P<0.05]; the detection rate of para-aortic SLN in the cervical injection group (28%, 7/25) was significantly lower than those in the intrauterine injection group and combined injection group [52% (11/21) and 67% (18/27), respectively; both P<0.05]. Among 73 cases with endometrial cancer, 9 had lymph node metastasis confirmed by postoperative pathological examination, 8 of them had lymph node metastasis detected by SLN and 1 had no lymph node metastasis detected by SLN, with a total sensitivity of 89% and a negative predictive value of 98%. The sensitivity and negative predictive value of cervical injection group and combined injection group were 100%, while the sensitivity and negative predictive value of intrauterine injection group were 67% and 95%. Among 56 low-risk patients, only one patient with lymph node metastasis was confirmed by postoperative pathology by SLN detection, and the metastasis rate was 2% (1/56), and the sensitivity and negative predictive value were 100%. Lymph node metastasis was confirmed in 8 of 17 patients (8/17) with a sensitivity of 88% and a negative predictive value of 90%. (2) A total of 459 SLN were detected in 73 endometrial cancer patients, with the highest proportion of external iliac (33.3%, 153/459).The obturator foramen was 25.3% (116/459), para-aortic 19.6% (90/459), iliac 12.0% (55/459), and presacral 9.8% (45/459). The proportion of para-aortic SLN in the cervical injection group was 12.4% (21/169), which were significantly lower than that in the intrauterine injection group and the combined injection group [27.4% (26/95) and 22.1% (43/195), respectively; both P<0.05]. (3) Pathological super-staging results: among 64 patients with negative SLN routine paraffin pathology, 4 cases of lymph node micro-metastases and 1 case of isolated tumor cell metastasis were detected, and the SLN micro-metastases rate was 8% (5/64), including 2 cases of low-risk patients and 3 cases of medium-high risk patients. Conclusions: SLN biopsy has high sensitivity and negative predictive value in patients with early endometrial cancer and could be used as an alternative to systematic lymph node dissection in low-risk patients. The SLN mapping through cervical-uterine combined injection could further improve the detection rate effectively and avoid the missed detection of positive para-aortic lymph node, especially for high-risk patients or patients with fundal tumor involvement.

[The application value of cardiac magnetic resonance quantitative T1 mapping technique for risk stratification in patients with pulmonary arterial hypertension].

Objective: To explore the application value of cardiac magnetic resonance (CMR) native T1 mapping for risk stratification in patients with pulmonary arterial hypertension (PAH). Methods: A total of 59 patients with diagnosed PAH and clear-documented risk status in Peking Union Medical College Hospital and underwent CMR examination between January 2019 and December 2021 were retrospectively included, which including 12 males and 47 females, aged from 4 to 77 (31±13) years. Those patients were subdivided into two groups based on the clinically-assessed risk status: low-risk group (n=30) and intermediate-/high-risk group (n=29). Twenty-five healthy individuals were included as controls. Base, midventricular, and apical inferior right ventricular insertion point (IRVIP) native T1 values on short axis images were measured. Native T1 values in PAH patients and control group, in low-risk group and intermediate-/high-risk group were compared, respectively, and receiver operating characteristics (ROC) curves with area under the curves (AUC) were calculated to evaluate the application value of native T1 values for risk stratification in PAH patients. Results: Base, midventricular and apical IRVIP native T1 of PAH patients were all significantly increased as compared to controls [Base:(1 439.31±129.96) vs (1 282.36±37.18) ms;midventricular:(1 450.32±111.55) vs (1 287.56±53.16) ms;apical:(1 444.12±109.15) vs (1 266.36±75.31) ms](all P<0.001). The midventricular IRVIP native T1 values were significantly higher in patients in intermediate-/high-risk status as compared to those in low-risk status [ (1 493.24±126.32) vs (1 428.50±85.73) ms,P=0.026]. The AUC of mid ventricle IRVIP native T1 for distinguishing patients in intermediate-/high-risk status was 0.741. The base [(1 458.21±134.96) vs (1 421.03±104.75) ms, P=0.241] and apical [(1 465.90±125.36) vs (1 423.07±87.87) ms,P=0.136] IRVIP native T1 values in patients in intermediate-/high-risk group were also numerically higher as compared with patients in low-risk status, however, without statistical significant (both P>0.05). Conclusion: Midventricular IRVIP native T1 value might have a role for assisting in risk stratification in PAH patients, which was clinically significant for facilitating the work-up and prognosis improvement of PAH patients.

[Coronary CT angiography derived fractional flow reserve: view from radiologist].

The diagnosis of coronary artery disease depends on a comprehensive assessment including morphological and functional information. Coronary CT angiography derived fractional flow reserve (CT-FFR) could obtain morphological and functional information from a single coronary CT angiography (CCTA) scan, achieving a "one-stop" assessment of coronary artery disease. CT-FFR is a non-invasive imaging examination to assess the hemodynamic changes of focal coronary lesions and suitable for patients with moderate to severe coronary artery stenosis or mild coronary artery stenosis combined with other high-risk characteristics, to assist in determining whether the lesions cause myocardial ischemia, and to guide clinical decisions and predict the risk of cardiovascular events. The application of CT-FFR relies on satisfied image quality of CCTA, and requires the cooperation of radiologists, clinicians and patients. This paper describes from the aspects of the measurement and analysis of CT-FFR, the diagnostic value of CT-FFR, the value of CT-FFR in assisting clinical decision making and prognosis, the comparison of CT-FFR with other functional cardiovascular imaging techniques and the future perspectives.

[Autopsies and placental examinations of perinatal fetal deaths: a clinicopathological analysis of 105 cases].

Objective: To summarize the clinicopathological factors related to perinatal fetal death and to evaluate importance of fetal autopsy and placental pathology. Methods: The clinicopathological data of 105 perinatal fetal deaths in Beijing Haidian Maternal and Child Health Hospital from November 2012 to December 2020 were retrospectively analyzed. Relevant literature was also reviewed. Results: The maternal age of the deceased fetuses ranged from 22 to 43 years with the average (31.35±4.04 years), and the gestational weeks were 28-40+6 weeks. Among them, 101 were singleton cases and 4 twin cases. 103 fetuses died in uterus and 2 died during delivery. Relevant factors analysis of the 105 perinatal fetal deaths showed that 86 cases (81.9%, 86/105) were related to umbilical cord/placental abnormality, 10 cases (9.5%, 10/105) uterine infection, 6 cases (5.7%, 6/105) fetal factors, 1 case was fetal maternal blood transfusion syndrome, 1 case twin blood transfusion syndrome, and 1 case died of complete uterine rupture. Among the 86 cases related to umbilical cord/placental abnormality, the diagnosis was most often based on the gross examination of placenta. The most common cause of death was umbilical cord torsion with thin root, followed by placental abruption, tight umbilical cord winding, vascular rupture and umbilical cord true knot. The morphology of placenta revealed mainly functional changes. Among the 10 cases related to intrauterine infections, the placenta generally showed lobular placental edema. The morphological characteristics of ascending infection were mainly acute chorioamnionitis, and the morphological characteristics of blood-borne infection were mainly acute or chronic villitis, as well as villous interstitial inflammation. Identification of viral inclusions suggested viral etiology, while the final diagnosis was relied on laboratory testing. Among the 6 cases related to fetal abnormality, the diagnostic value of placenta was limited and the diagnosis could be made with fetal autopsy. Conclusion: The causes of perinatal fetal death are complex, diverse, and often the synergistic result of multiple factors. Fetal autopsy and placental pathology are the key technical means to identify the cause of death and deserve more attention and utilization.

[Clinical characteristics of arrhythmia-onset sarcoidosis cases].

Objective: To describe the clinical characteristics of sarcoidosis patients with arrhythmia as the primary or main manifestation. Methods: We conducted a retrospective analysis of arrhythmia-onset sarcoidosis cases between January 2017 and December 2020. Their clinical manifestations, radiological features, treatment and prognosis were reviewed and analyzed. Results: This study consisted of 3 females and 1 male, with a mean age of 51 years (range from 42 to 58 years old). Arrhythmia was the first or main clinical manifestation for all 4 cases, involving Ⅲ° atrioventricular block (AVB) (n=1), Ⅱ° type Ⅱ AVB (n=1), and frequent ventricular premature beats and short array ventricular tachycardia (n=2). Three cases were diagnosed with respiratory sarcoidosis simultaneously during the diagnostic evaluation for arrhythmia. One case was diagnosed with sarcoidosis because of abnormal chest CT images due to cervical lymph node enlargement 5 years after arrhythmia. All 4 cases were confirmed as presenting epithelioid cell granulomatous inflammation by bronchoscopic biopsies. Late gadolinium enhancement with cardiac magnetic resonance (LGE-CMR) imaging was arranged for two cases. Both of them had typical imaging findings of cardiac sarcoidosis. Three cases were confirmed of cardiac involvement through positron emission computed tomography (PET)-CT. None of the enrolled four cases were arranged with endomyocardial biopsy. All four cases were improved with oral corticosteroids, immunosuppressants and anti-arrhythmic medications. Two cases underwent cardiac pacemaker implantation. Conclusions: The possibility of cardiac sarcoidosis should be considered in middle-aged and elderly patients with unexplained high-degree AVB or ventricular arrhythmia. Chest CT is recommended for routine screening for those cases. LGE-CMR and/or PET-CT is recommended for them to confirm the diagnosis of cardiac sarcoidosis. Corticosteroids and immunosuppressants are effective for these patients.

[Singleton placentas with abnormal shape: a clinicopathological analysis of 130 cases].

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29+5 to 40+4 weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.

Lif Deficiency Leads to Iron Transportation Dysfunction in Ameloblasts.

Leukemia inhibitory factor (LIF), a member of the interleukin 6 family of cytokines, is involved in skeletal metabolism, blastocyst implantation, and stem cell pluripotency maintenance. However, the role of LIF in tooth development needs to be elucidated. The aim of the present study was to investigate the effect of Lif deficiency on tooth development and to elucidate the functions of Lif during tooth development and the underlying mechanisms. First, it was found that the incisors of Lif-knockout mice had a much whiter color than those of wild-type mice. Although there were no structural abnormalities or defective mineralization according to scanning electronic microscopy and computed tomography analysis, 3-dimensional images showed that the length of incisors was shorter in Lif-/- mice. Microhardness and acid resistance assays showed that the hardness and acid resistance of the enamel surface of Lif-/- mice were decreased compared to those of wild-type mice. In Lif-/- mice, whose general iron status was comparable to that of the control mice, the iron content of the incisors was significantly reduced, as confirmed by energy-dispersive X-ray spectroscopy (EDS) and Prussian blue staining. Histological staining showed that the cell length of maturation-stage ameloblasts was shorter in Lif-/- mice. Likewise, decreased expression of Tfrc and Slc40a1, both of which are crucial proteins for iron transportation, was observed in Lif-/- mice and Lif-knockdown ameloblast lineage cell lines, according to quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Moreover, the upregulation of Tfrc and Slc40a1 induced by Lif stimulation was blocked by Stattic, a signal transducer and activator of transcription 3 (Stat3) signaling inhibitor. These results suggest that Lif deficiency inhibits iron transportation in the maturation-stage ameloblasts, and Lif modulates expression of Tfrc and Slc40a1 through the Stat3 signaling pathway during enamel development.

[A review on the epidemiology of severe fever with thrombocytopenia syndrome].

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease discovered in the 21st century. This disease has been reported in several Asian countries, including China, Japan, South Korea, Vietnam, and Myanmar. Until 2019, SFTS cases have been reported in 25 provinces in China, and most of them were rural residents from mountains and hilly regions. Most SFTS cases were sporadic but geographically concentrated, mainly in Henan, Shandong, Anhui, Hubei, Liaoning, Zhejiang, and Jiangsu provinces. SFTSV infection was transmitted predominantly by a tick bite and potentially through close contact with the patient's blood or body fluids. Fever, gastrointestinal symptoms, thrombocytopenia, and leukopenia were common initial manifestations, and multiple organ failure or even death could occur in severe cases. The reported cases of SFTS have been gradually increasing, and the case fatality rate has remained at a high level, posing a severe threat to public health in China. This paper reviewed the epidemiological features, risk factors for disease transmission, and the clinical characteristics of SFTS to gain further knowledge of the disease, guide the prevention and management, and help reduce the case fatality rate.

[Deep learning reconstruction algorithm for coronary CT angiography in assessing obstructive coronary artery disease caused by calcified lesions: the clinical application value].

Objective: To investigate the image quality of coronary CT angiography (CCTA) subjected to deep learning-based reconstruction algorithm (DLR) method and its diagnostic performance for stenosis caused by coronary calcified lesions. Methods: We enrolled 33 consecutive patients with known or suspected coronary artery disease (CAD) who underwent CCTA and subsequently invasive coronary angiography (ICA) within 1 month in the department of radiology, Peking Union Medical College Hospital between February 2020 and February 2021. Among them, there are 26 males and 7 females, age range from 45 to 86 (61.9±9.0) years. The CCTA images were reconstructed with DLR and hybrid iterative reconstruction (HIR). Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated on the aorta root, left main artery, proximal left anterior descending, left circumflex, and right coronary artery of the CCTA images and were used to evaluate the objective image quality (IQ). Subjective IQ score was graded using Likert four-point scale (1 for excellent and 4 for poor). The diagnostic performance of obstructive coronary artery disease caused by calcified lesions on CCTA subjected to DLR and HIR methods were evaluated using ICA as the reference standard. Results: A total of 123 lesions in 33 patients were included in the analysis. Image noise of DLR image was significantly lower than that on HIR image(defined as the standard deviation of the attenuation values in the aortic root: 18.12±3.66 vs 24.19±5.71, P<0.001), CNR and SNR of DLR image in the aortic root were higher (CNR:43.83±23.73 vs 26.38±9.69, P<0.001,SNR:26.66±7.83 vs 21.23±8.65, P<0.001). Subjective scores of DLR was better than HIR image (1.12±0.41 vs 1.46±0.60,P<0.001). The sensitivity, specificity and accuracy of DLR and HIR images for diagnosing obstructive coronary artery disease caused by calcified lesions were 100.0%, 77.4%, 78.9% and 100.0%, 63.5%, 65.9%%, respectively. The number of false positive cases on DLR image decreased by 38% compared with HIR. Conclusions: Artificial intelligence based DLR can significantly reduce the image noise and improve the image quality of CCTA. DLR helps to improve the diagnostic performance of CCTA in assessing obstructive coronary artery disease caused by calcified lesions, which may have good clinical application value.

[Application of acellular dermal matrix loaded collagen binding domain-vascular endothelial growth factor patch in urethral wound repair in beagles].

Objective: To investigate the application value of acellular dermal matrix (ADM) loaded collagen binding domain-vascular endothelial growth factor (CBD-VEGF) patch in the repair of urethral wound in beagles. Methods: Twenty-one healthy adult beagles were selected to establish urethral wound model and randomly divided into 3 groups, which were treated with different repair methods. CBD-VEGF patch was prepared and instantaneous implantation was performed as the models were successfully built. The blank control group was treated without any repair materials;the ADM group was treated with collagen patch for repair and the ADM loaded with CBD-VEGF group was treated with collagen patch loaded with VEGF for repair. The safety and effectiveness of the three groups of materials implanted into the urethral wound model at 6 months after surgery were compared. Urodynamic examination, urethral angiography and pathological examination were used to evaluate the recovery of urethral tissue in the three groups. Result: Compared with blank control group and ADM patch group, there was no complications or other adverse conditions in the ADM-loaded CBD-VEGF patch group. Urethrography was performed to measure the diameter of the urethra in the experimental segment, the mean urethral diameter of blank control group [(3.07±0.43) mm] was significantly smaller than that of ADM patch group [(3.73±0.11) mm] and ADM loaded CBD-VEGF patch group [(3.64±0.32) mm], with statistical difference (P<0.05). Pathological examination with HE and Masson staining showed more proliferative blood vessels in the ADM loaded CBD-VEGF patch group. HE staining indicated that there were more proliferative vessels in the group of CBD-VEGF patch loaded with ADM. Masson staining showed that the positive area percentage of collagen tissue in the three groups was 34.27%±7.40%, 29.08%±3.79% and 28.02%±2.39%, respectively, with no statistical difference between the three groups(all P>0.05). There was no excessive deposition of collagen tissue in the two groups using collagen patch. The percentage of positive staining per unit area in the three groups were 1.4%±0.1%,1.8%±0.1%3.1%±0.2%, respectively, and the difference was statistically significant among three groups and between every two groups (all P<0.01), indicating the vascular density of CBD-VEGF group loaded with ADM was the highest. Conclusion: ADM loaded CBD-VEGF patch is a good biological support material for covering the wound after urethral surgery, and it provides an alternative direction for promoting the healing of the urethral wound.