Hypertension and its association to phenotype on left ventricular function in hypertrophic cardiomyopathy patients assessed by cardiovascular magnetic resonance imaging.

AIM: The impact of hypertension (HT) on phenotypic expression in individuals with hypertrophic cardiomyopathy (HCM) is unclear. MATERIALS AND METHODS: Thirty-six HCM individuals without HT, 27 HCM with HT, and 20 age- and sex-matched healthy controls who underwent cardiovascular magnetic resonance imaging (CMR) to evaluate left ventricular (LV) function and strain were enrolled. Three groups' LV function and strain were compared. We also investigated whether HT was associated with reduced LV strain in HCM patients using univariate and multivariate linear regression analyses. RESULTS: HCM (with/without HT) patients had higher LV mass and LV mass index than the normal controls group. Furthermore, global radial strain, global circumferential strain (GCS), global longitudinal strain, global peak systolic strain rate of radial, and global peak diastolic strain rate of radial were significantly lower in HCM patients with HT, intermediate in HCM patients without HT, and greater in the normal controls (all, P<0.05). Worse GCS was observed in HCM patients with HT than those without HT (P<0.05). Multivariable linear regression analysis showed that HT was independently associated with impaired LV ejection fraction and reduced strain (all P<0.05). CONCLUSION: The presence of HT was associated with an adverse phenotype, including worse ejection fraction and reduced strains in HCM patients. In addition, management of HT and its effect on the clinical outcomes in HCM patients needs to be studied.

[Effect of preemptive analgesia with ibuprofen on postoperative pain after mandibular third molar extraction: a randomized controlled trial].

Objective: To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application. Methods: This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively. Results: All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] (Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] (Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] (Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively (P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] (Z=-2.81, P=0.005). Conclusions: A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Voltage-Controlled Magnon Transistor via Tuning Interfacial Exchange Coupling.

Magnon transistors that can effectively regulate magnon transport by an electric field are desired for magnonics, which aims to provide a Joule-heating free alternative to the conventional electronics owing to the electric neutrality of magnons (the key carriers of spin-angular momenta in the magnonics). However, also due to their electric neutrality, magnons have no access to directly interact with an electric field and it is thus difficult to manipulate magnon transport by voltages straightforwardly. Here, we demonstrated a gate voltage (V_{g}) applied on a nonmagnetic metal and magnetic insulator (MI) interface that bent the energy band of the MI and then modulated the probability for conduction electrons in the nonmagnetic metal to tunnel into the MI, which can consequently enhance or weaken the spin-magnon conversion efficiency at the interface. A voltage-controlled magnon transistor based on the magnon-mediated electric current drag (MECD) effect in a Pt-Y_{3}Fe_{5}O_{12}-Pt sandwich was then experimentally realized with V_{g} modulating the magnitude of the MECD signal. The obtained efficiency (the change ratio between the MECD voltage at ±V_{g}) reached 10%/(MV/cm) at 300 K. This prototype of magnon transistor offers an effective scheme to control magnon transport by a gate voltage.

[Clinical characteristics and surgical outcomes in pediatric progressive restrictive strabismus].

Objective: To investigate the clinical features, imaging manifestations, histopathological characteristics, and surgical outcomes in pediatric progressive restrictive strabismus. Methods: A retrospective case series study was conducted, including data from 9 cases (9 eyes) of pediatric progressive restrictive strabismus treated at Tianjin Eye Hospital from June 2017 to October 2022. The study compared the degree of globe protrusion in both eyes, changes in eyelid fissure height during internal and external rotation in the primary gaze, summarized clinical characteristics, and analyzed intraoperative conditions, surgical outcomes and postoperative histopathological results of strabismus correction surgery. Statistical analysis was performed using Wilcoxon signed-rank test and Friedman two-way analysis of variance. Results: All 9 cases involved unilateral onset, with 4 males and 5 females. Three cases affected the right eye, and six affected the left eye. Onset age ranged from 2 to 40 months. The degree of globe protrusion in the affected eyes was 13.00 (12.00, 13.00) mm for the right eye and 12.00 (12.00, 13.50) mm for the left eye, with no statistically significant difference (Z=-1.00, P=0.317). There were no significant changes in eyelid fissure height during internal rotation [8.00 (7.25, 8.00) mm], primary gaze [7.50 (7.00, 8.00) mm], and external rotation [8.00 (7.75, 8.00) mm] in the affected eyes (χ²=1.00, P=0.607). No apparent abnormalities were observed in head CT or MRI scans, serum, or immunological tests. However, orbital CT or MRI scans indicated thickening of different extraocular muscle bellies. Six out of nine cases underwent strabismus correction surgery, and postoperative examination revealed restriction in eye movement despite achieving orthophoria in the primary gaze. Tissue pathology of three cases showed increased collagen fiber proliferation in one, scattered bundles of smooth muscle fibers amid diffuse collagen fiber proliferation in another, and abnormal proliferation of striated muscle fibers with varying diameters, increased paired box (PAX)7-positive satellite cells expressing slow muscle myosin in the third case. Conclusions: Pediatric progressive restrictive strabismus presents with restrictive changes, without significant alterations in globe protrusion and eyelid fissure height. Imaging examinations reveal thickening of the extraocular muscle bellies in the affected eye. Although strabismus correction surgery improves eye position, postoperative eye movement remains restricted. Histopathological findings in some cases show abnormal proliferation of skeletal muscle fibers or collagen fibers.

[Update points for the 2022 edition of the European Association for the Study of Liver Diseases Clinical Practice Guidelines for the Management of Hepatic Encephalopathy and comparison with China's 2018 edition guidelines].

The European Association for the Study of Liver Diseases issued the "Clinical Practice Guidelines for the Management of Hepatic Encephalopathy" in 2022, which included recommendations for clinical diagnosis, assessment, treatment, management, and prevention. The Society's "Hepatic Encephalopathy Clinical Practice Guidelines in Chronic Liver Disease," which was last published in 2014, and the "Guidelines for the Diagnosis and Treatment of Hepatic Encephalopathy in Cirrhosis," which the Chinese Society of Hepatology, Chinese Medical Association, released in 2018, have certain differences and updates in terms of comparison to terminology, grading and classification, diagnosis, clinical evaluation and treatment, management, and prevention. Herein, the updated points of this guideline and the differences between it and our nation's guidelines are summarized in order to refine and understand the guiding role of the new version of the guideline for the clinical treatment of hepatic encephalopathy and provide aid for standardizing clinical diagnosis and treatment.

An interpretable machine learning model for real-time sepsis prediction based on basic physiological indicators.

OBJECTIVE: In view of the important role of risk prediction models in the clinical diagnosis and treatment of sepsis, and the limitations of existing models in terms of timeliness and interpretability, we intend to develop a real-time prediction model of sepsis with high timeliness and clinical interpretability. PATIENTS AND METHODS: We used eight real-time basic physiological monitoring indicators of patients, including heart rate, respiratory rate, oxygen saturation, mean arterial pressure, systolic blood pressure, diastolic blood pressure, temperature and blood glucose, extracted three-hour dynamic feature sequences, and calculated 3 linear parameters (mean, standard deviation, and endpoint value), a 24-dimensional feature vector was constructed, and finally a real-time sepsis prediction model was constructed based on the Local Interpretable Model-Agnostic Explanation (LIME) interpretability method. RESULTS: The area under the receiver operating characteristic curve (AUROC), Accuracy and F1 scores of Extremely Randomized Trees we built were higher than those of other models, with AUROC above 0.76, showing the best performance. The Imbalance XGBoost has a high specificity (0.86) in predicting sepsis. The LIME local interpretable model we built can display a large amount of valid model prediction details for clinical workers' reference, including the prediction probability and the influence of each feature on the prediction result, thus effectively assisting the work of clinical workers and improving diagnostic efficiency. CONCLUSIONS: This model can provide real-time dynamic early warning of sepsis for critically ill patients under supervision and provide a reference for clinical decision support. At the same time, interpretive analysis of sepsis prediction models can improve the credibility of the models.

[A biography of infectious diseases: Hans Zinsser and his Rats, Lice and History].

Hans Zinsser, a well-known bacteriologist and immunologist in the United States in the early 20th century, made great advancement in the research of pathogen of typhus and its vaccine, with the epidemic typhus renamed after him. His masterpiece, Rats, Lice and History, teased out the co-evolutionary process of infectious diseases and their related organisms, focusing on specific cases and the development history of typhus. In this sense, he revealed the tremendous impact of infectious diseases on human history. He examined microorganisms and humans equally rather than simply from a human point of view. He analysed the pathological features of infectious diseases and provided professional insights into historical events of infectious diseases, such as the origin of syphilis and the plague of Athens, based on sufficient citations and references. He also advocated interpreting the history of infectious diseases with a holistic insight of history. His book, Rats, Lice and History, has been reprinted many times after its first publication, driving the following scholars to put the history of infectious diseases into a grand background of human development, enhancing the comprehension of ecology and politics and promoting the development of research in the history of diseases including life sciences, history and other disciplines.

[Using the external auditory canal skin graft of the healthy side to treat unilateral congenital aural atresia: preliminary results of clinical research].

Objective: To investigate whether the contralateral normal external auditory canal (EAC) skin graft can maintain the ear canal health after EAC reconstruction in unilateral congenital aural atresia (CAA) cases. Methods: A Zelen design randomized controlled study was used to collect unilateral CAA patients for EAC reconstruction prospectively (clinical trial registration number: ChiCTR2000032103). The patients were randomly divided into the control group and the trial group. The trial group used the contralateral normal EAC skin graft group (transplant part of the contralateral normal EAC skin to repair the atresia side for unilateral CAA patients), the control group all used scalp blade thick skin. We observed the EAC health and hearing results of the two groups after EAC reconstruction. Results: A total of 13 cases were enrolled from July 2020 to August 2021. There were eight patients in the trial group, including six males and two females, with an average age of 22.3 years (14-36 years). There were two patients with CAA on the left and six patients on the right. The average follow-up time was 8.8 months (4-14 months). There were five patients in the control group, all cases were male with an average age of 16.2 years (12-20 years). There were four patients with CAA on the left and one patient on the right. The average follow-up time was 7.0 months (2-14 months). In the trial group, eight cases of reconstructed EAC epithelium were healthy, one patient had cicatricial stenosis of EAC opening and lateralization of the tympanic membrane. The other patient had cicatricial stenosis of reconstructed EAC, this case also had scar hyperplasia of the contralateral EAC opening but recovered after soft packing and triamcinolone acetonide injection treatment. The healthy side EAC of the rest trial group had no scarring stenosis or local bone hyperplasia during long-term follow-up. In the control group, one patient was lost to follow-up and the other four patients had dry ears of reconstructed EAC, but easily to form crusts and needed to be cleaned repeatedly, one patient had lateralization of the tympanic membrane, the EAC epithelium was not healthy for long-term follow-up. The incidence of complications related to EAC reconstruction was lower than previous studies (χ²=5.55, P=0.018), and the average postoperative Air-Bone Gap increased (18.8±10.0)dB. Conclusion: By optimizing the EAC reconstruction technology, the health of the reconstructed EAC is improved compared with the previous study. After active intervention and treatment, there should be no scarring stenosis or local bone hyperplasia on the contralateral side EAC.

[Clinical study of selection of the upper instrumented vertebra at one level caudal to upper end vertebra in patients with Lenke 5C adolescent idiopathic scoliosis].

Objective: To investigate whether the upper instrumented vertebra (UIV) can be selected at one level caudal to upper end vertebra (UEV) in Lenke type 5C adolescent idiopathic scoliosis (AIS) patients. Methods: Total of 28 Lenke 5C AIS patients who underwent selective posterior fusion in Drum Tower Hospital of Nanjing University Medical School from September 2013 to September 2015 were included. There were 4 males and 24 females, with an age of (15.0±2.0) years, the Risser sign was graded 2-5. The following imaging parameters were measured on standing full spine X-ray before, immediately after the surgery and at the last follow-up: thoracolumbar/lumbar (TL/L) Cobb angle, coronal balance, UIV translation, lower instrumented vertebra (LIV) translation, UIV tilt, LIV tilt, and thoracic apical vertebral translation (T-AVT), lumbar apical vertebral translation (L-AVT). The patients were divided into two groups: decompensation group (n=6) and non-decompensation group (n=22). Radiographic parameters and Scoliosis Research Society (SRS)-22 scores were compared between the two groups. Results: Six cases (21.4%) had proximal decompensation at the last follow-up. There were no significant differences in Risser grade(3.8±1.0 vs 3.6±1.6), baseline thoracic Cobb angle(25.8°±2.2° vs 26.3°±6.4°) and TL/L Cobb angle(43.7°±3.4° vs 45.2°±6.5°) between the two groups (all P>0.05). However, the baseline lumbar/thoracic apical vertebra translation (L-T AVT ratio) was significantly higher in patients with proximal decompensation (6.3±1.3 vs 4.0±2.0, P=0.048). Conclusion: Selecting UIV at one level caudal to UEV, would not increase the incidence of proximal decompensation in Lenke 5C AIS patients with Risser higher than grade 2, the smaller baseline L-T AVT ratio, and with thoracic compensatory curve over 15°, and can obtain satisfactory clinical results.

[Occurrence of rod fracture and salvage methods after primary surgery of the congenital lumbosacral deformity associated with sacral agenesis].

Objective: To analyze the occurrence of rod fracture after surgery for lumbosacral deformity associated sacral agenesis and discuss the relevant salvage methods. Methods: The clinical records of 19 patients who underwent surgical treatment for lumbosacral deformity associated sacral agenesis from January 2001 to January 2018 were retrospectively reviewed, including 11 boys and 8 girls. The average age was (9.6±5.2) years. The outcomes of surgical correction and internal fixation were evaluated by postoperative regular follow-up. We also recorded the time and position of rod fracture occurrence. The Cobb angle, coronal balance and sagittal balance were measured and compared to analyze the corresponding salvage methods and revision outcomes. Results: Three patients encountered rod fracture during follow-up, so the incidence of rod fracture after surgery for lumbosacral deformity associated sacral agenesis was 15.8%(3/19). Based on their own conditions, we formulated the individualized strategy and performed the revision surgery through the posterior-only approach. The most critical step was abundant bone-grafting and fusion in the defected sacroiliac joint. After revision, the scoliotic Cobb angle improved in two patients (91.5° vs 47.5°, 49.0° vs 28.0°) and coronal balance improved in one patient (40.3 mm vs 24.3 mm). No complication reoccurred during follow-up. Conclusion: The rod fracture after surgery for lumbosacral deformity associated sacral agenesis is quite common, which is probably correlated with its unique deformed structure and biomechanical characteristics. The individualized salvage methods and adequate bone-grafting and fusion for the defected sacroiliac joint will guarantee the reconstruction and maintenance of spine balance after revision.

[Correction of severe cup ears using postauricular tongue-shaped flap combined with deep fascial suspension].

Objective: To investigate the effect and satisfaction of using the postauricular tongue-shaped flap combined with deep fascia suspension in correcting severe cup ear malformation. Methods: Between August 2018 and November 2019, nine cases (10 ears) of Tanzer type Ⅲ severe cup ear malformation were treated with postauricular tongue-shaped flap combined with deep fascia suspension in this study. Results: Nine cases primary healed without hematoma, infection or skin necrosis, except one case with postoperative incision dehiscence. The cup ear deformity was significantly improved after the operation, the helix was intact, and the anti-helix was visible. The length, width, and circumference of the auricle were significantly enlarged three months following surgeries. There were no other complications except 1 patient recurrence 12 months after surgery. The patients were highly satisfied with the results of the surgery. Conclusions: Although the aesthctic of the reconstructed auricle is insufficient, this new technology makes full use of the autologous auricle tissue to correct severe cup ear malformation with good results.

Upregulation of KCNMA1 facilitates the reversal effect of verapamil on the chemoresistance to cisplatin of esophageal squamous cell carcinoma cells.

OBJECTIVE: This study aimed to investigate the reversal effect of verapamil (VER) on the chemoresistance to cisplatin of esophageal squamous cell carcinoma (ESCC) cells. PATIENTS AND METHODS: The reversal effect of VER on cisplatin resistance in ESCC cells was evaluated via CCK-8 assay, colony formation assessment, and flow cytometry. The key genes that mediate this effect were screened via high-throughput transcriptome se¬quencing. The mRNA and protein expression levels of potassium calcium-activated channel subfamily M alpha 1 (KCNMA1) in ESCC cells were examined via quantitative real-time PCR and Western blot analysis, respectively. The protein expressions of KCNMA1 in tissue samples from patients with either positive or negative responses to the therapeutic regimen of VER were determined via immunohistochemistry assay. Cell models with KCNMA1 knockdown and overexpression were es¬tablished to examine the role of KCNMA1 in mediating the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells. RESULTS: Results revealed that VER significantly decreased the 50% inhibitory concentration of cisplatin, inhibited colony formation, and induced apoptosis in ESCC cells. The curative effects of VER combined with chemotherapeutic drugs in KCNMA1-positive patients were better than those in KCNMA1-negative patients. KCNMA1 upregulation enhanced the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells. CONCLUSIONS: KCNMA1 facilitated the reversal effect of VER on cisplatin resistance in ESCC cells.

[Analysis of BK virus infection in kidney transplant recipients].

Objective: To compare the infection of BK virus in the recipients of living donor(LD) kidney transplant and deceased donor(DD) kidney transplant. Methods: A total of 911 recipients who underwent kidney transplantation in the Organ Transplantation Research Institute of the 8th Medical Center of the People's Liberation Army General Hospital from January 2015 to August 2019 were enrolled in this study. The DNA copies of BK virus in urine and peripheral blood of kidney transplant recipients were detected by real-time quantitative PCR. The patients were divided into LD group (n=255) and DD group (n=656). BK virus infection in recipients with DD kidney transplant were compared with that in recipients of LD kidney transplant. Results: The BK virus positive rate in the urine of all subjects was 13.06%(119/911), and that in blood was 2.96% (27/911). The positive rate of BK virus in urine after kidney transplantation was significantly higher than that in blood(P<0.000 1). The positive rate in urine was 9.02% (23/255) in LD group, which was significantly lower than that of 14.63% (96/656) in DD group in the same period (χ(2)=5.097, P=0.012); The positive rate of BK virus infection in relatives group was 0.78% (2/255), which was significantly lower than that of 3.81% (25/656) in DD group (χ(2)=5.849, P=0.007). Conclusions: There was a significant difference in the infection rate of BK virus between the LD and DD group. The incidence of BK virus infection in kidney transplant recipients from DD was higher than that of from LD kidney transplant recipients.

Effect of verapamil in the reversal of doxorubicin chemotherapy resistance in advanced gastric cancer.

OBJECTIVE: Gastric carcinoma is one of the most common malignant tumors and one of the most common cancer-related fatal diseases. Chemotherapy is considered as the major therapy for advanced gastric cancer, and the curative effect of chemotherapy directly affects the treatment of advanced gastric cancer. Drug resistance of tumor cells is one of the important causes that induces failure of chemotherapy. Previous studies have demonstrated that verapamil (VER) can reverse drug resistance by inhibiting the P-glycoprotein (P-gp), which is one of the main targets of VER. The present study aimed at investigating the function of glucosylceramide synthase (GCS) in the VER-induced reversal of doxorubicin (ADM) chemotherapy resistance in gastric carcinoma. PATIENTS AND METHODS: In the current study, the 4 GC cell line was selected for investigation. The IC50 values of gastric cancer cells were measured using CCK-8 assay. The expression levels of candidate genes in gastric carcinoma cells were measured by RT-qPCR. The expression levels of candidate protein in gastric carcinoma cells were measured by Western blot. The expression of GCS protein in clinical specimens of GC receiving VER+TACE therapy was measured by immunohistochemistry. The test of gastric carcinoma cell apoptosis was measured by Annexin V-FITC/PI double-staining. RESULTS: We found that the expression levels changes of the GCS gene can influence the effects of ADM+VER on cell apoptosis. The role and mechanism of GCS gene in reversing the chemotherapy resistance of gastric carcinoma cells to ADM were explored. CONCLUSIONS: In future research, we will explore the mechanism of how GCS affects drug resistance in gastric carcinoma and related signal transduction pathway.

Denitrosylation of nNOS induced by cerebral ischemia-reperfusion contributes to nitrosylation of CaMKII and its inhibition of autophosphorylation in hippocampal CA1.

OBJECTIVE: The aim of this study is to investigate the relation between CaMKII S-nitrosylation and its activation, as well as the underlying mechanism, after global cerebral ischemia-reperfusion. MATERIALS AND METHODS: The rat model of cerebral ischemia-reperfusion was established by four-vessel occlusion of 15 min and reperfusion of different times. nNOS inhibitor 7-nitroindazole (7-NI), exogenous nitric oxide donor GSNO (nitrosoglutathione), or N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 were administered before ischemia. The expressions of S-nitrosylation and phosphorylation of CaMKII and nNOS were detected by biotin switch assay, immunoblotting, and immunohistochemical staining after cerebral ischemia-reperfusion. The survival of hippocampal CA1 pyramidal cells after administration of the three drugs was examined by cresyl violet staining. RESULTS: Following cerebral ischemia-reperfusion, the S-nitrosylation of CaMKII was increased, accompanied by a decrease of phosphorylation, suggesting a decrease of activity (p<0.05). Meanwhile, the phosphorylation and S-nitrosylation of nNOS were notably decreased at the same time point (p<0.05). The administration of 7-NI, GSNO, and MK-801 increased the S-nitrosylation and phosphorylation of nNOS, leading to the attenuation of increased S-nitrosylation and decreased autophosphorylation of CaMKII after cerebral ischemia-reperfusion (p<0.05). Administration of MK-801, GSNO, and 7-NI significantly decreased the neuronal damage in rat hippocampal CA1 caused by cerebral ischemia-reperfusion (p<0.05). CONCLUSIONS: After cerebral ischemia-reperfusion, the decrease of autophosphorylation of CaMKII regulated by its S-nitrosylation may be due to the denitrosylation of nNOS and subsequent NO production. Increasing the phosphorylation of CaMKII by nNOS inhibitor, exogenous NO donor or NMDA receptor antagonist exerted neuroprotective effects against cerebral ischemia-reperfusion injury.