Efficacy and safety of transcatheter arterial chemoembolization combined with targeted therapy and immunotherapy in treatment of patients with stage Ⅱ‍b/Ⅲ‍a hepatocellular carcinoma based on China Liver Cancer Staging / 临床肝胆病杂志

ObjectiveTo evaluate the efficacy and safety of first-line transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy in the treatment of patients with stage Ⅱb/Ⅲa hepatocellular carcinoma （HCC） based on China Liver Cancer Staging （CNLC）. MethodsA total of 198 patients who received first-line TACE combined with targeted therapy and immunotherapy or received TACE alone from January 2015 to December 2022 in the First Affiliated Hospital of Soochow University were enrolled in this study， and after propensity score matching， there were 50 patients in combination group and 50 patients in TACE group. The Kaplan-Meier method was used to calculate median overall survival （mOS） and median progression-free survival （mPFS）. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate objective response rate （ORR） and disease control rate （DCR）， and Common Terminology Criteria for Adverse Events v5.0 was used to evaluate adverse events. The chi-square test was used for comparison of categorical data between two groups； the t-test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate survival time and calculate 95% confidence interval （CI）， and the Log-rank test was used for comparison of mOS and mPFS between two groups. ResultsThe combination group had an mOS of 30.1 months （95%CI： 21.9‍ ‍—‍ ‍38.3）， and the TACE group had an mOS of 14.5 months （95%CI： 11.0 ‍—‍‍ ‍18.0）， with a significant difference between the two groups （χ2=17.8， P<0.001）； the combination group had an mPFS of 10.3 months （95%CI： 8.8‍ ‍—‍ ‍11.8）， and the TACE group had an mPFS of 7.1 months （95%CI： 5.8‍ — ‍8.4）， with a significant difference between the two groups （χ2=10.4， P<0.001）. There were significant differences between the combination group and the TACE group in ORR （84% vs 58%， P<0.05） and DCR （94% vs 80%， P<0.05）. There was no significant difference between the combination group and the TACE group in the incidence rate of adverse events （24% vs 16%， P=0.317）， and no adverse event-related deaths were observed in either group. ConclusionCompared with TACE alone， TACE combined with targeted therapy and immunotherapy has a better efficacy in the treatment of patients with CNLC stage Ⅱb/Ⅲa HCC， without increasing the incidence rate of severe adverse events.

Effect of biological amniotic membrane soaked in pirfenidone on scar formation after glaucoma filtration surgery in rabbit eyes / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the application of biological amniotic membrane soaked in pirfenidone(PFD)and to evaluate its anti-scarring effect and toxic side effects on glaucoma model of rabbit eyes.METHODS: The right eyes of 72 healthy New Zealand white rabbits were randomly divided into 0.5%PFD+ biological amniotic membrane group, biological amniotic membrane group, mitomycin C(MMC)group and blank control group after the glaucoma model was established by anterior chamber injection of compound carbomer solution, and 18 rabbits in each group underwent trabeculectomy, in which the 0.5% PFD+ biological amniotic membrane group was placed with 0.5% PFD solution-soaked biological amniotic membrane under the scleral flap, and the biological amniotic membrane group was placed with normal saline-soaked rehydrated biological amniotic membrane under the scleral flap. In the MMC group, a cotton pad soaked in MMC was placed under the scleral flap for 3 min and immediately rinsed with normal saline, while the blank control group received no implant after the scleral flap was made. The intraocular pressure(IOP), filtration blebs, toxic side effects and complications were evaluated, and the histopathological changes in the filtration area were observed by hematoxylin-eosin(HE), Masson staining and immunohistochemical staining.RESULTS: The mean IOP at 14, 21 and 28 d after trabeculectomy were 0.5%PFD+ biological amniotic membrane group&#x0026;#x003C;MMC group&#x0026;#x003C;biological amniotic membrane group&#x0026;#x003C;blank control group(all P&#x0026;#x003C;0.05). At 28 d after trabeculectomy, 0.5%PFD+ biological amniotic membrane group had the best effect of anti-inflammatory hyperplasia and inhibition of collagen formation, the highest survival rate of filtration blebs, and the inflammatory reaction was mild.CONCLUSION: Biological amniotic membrane soaked in pirfenidone has more obvious anti-scarring effect on glaucoma model, with less toxic side effects and good safety.

The Effect of Modified Shugan Dingji Decoction （疏肝定悸汤） on the Occurrence of Endpoint Events in Patients with Paroxysmal Atrial Fibrillation of Liver Constraint and Qi Stagnation： A Retrospective Cohort Study / 中医杂志

ObjectiveTo retrospectively analyze the effect of modified Shugan Dingji Decoction （疏肝定悸汤） on the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation. MethodsA retrospective cohort study was conducted using the electronic medical record database of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine to screen and include patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation from January 1st， 2018， to December 31th， 2021. The included patients were divided into an exposure group and a non-exposure group， each consisting of 100 cases， based on whether they received modified Shugan Dingji Decoction. General information of the patients including age， gender， body mass index， duration of illness and comorbidities， medication history， cardiac structure and function indicators such as left atrial diameter， left ventricular end-diastolic diameter， stroke volume and ejection fraction， and the occurrence of endpoint events assessed through 24-hour dynamic electrocardiography or electrocardiogram to determine the recurrence of paroxysmal atrial fibrillation were collected. Kaplan-Meier （K-M） curves and Log-Rank tests were used to conduct survival analysis on the occurrence of endpoint events in the two groups of patients. Univariate and multivariate Cox regression analyses were used to analyze the impact of various factors on entry into endpoint events. Additionally， a safety assessment was performed by comparing liver and kidney function indicators before and after treatment. ResultsIn the non-exposure group， a total of 49 cases （49.0%） experienced endpoint events， while in the exposure group， there were 26 cases （26.0%）. The Log-rank test indicated significant difference between the two groups （χ2=11.211， P=0.001）. Univariate Cox regression analysis showed that age， duration of illness， hypertension， diabetes， chronic heart failure， left atrial diameter， stroke volume， and the use of modified Shugan Dingji Decoction may be the influencing factors for the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that the risk of endpoint events in the exposure group was significantly lower than that in the non-exposure group （P＜0.01）. Patients with a duration of illness ＞12 months had a significantly higher risk of endpoint events compared to those with a duration of illness ≤12 months （P＜0.01）. Patients without concomitant hypertension had a lower risk of endpoint events compared to those with hypertension （P＜0.05）. Patients with left atrial diameter ＞40 mm had significantly higher risk of endpoint events than those with left atrial diameter ≤40 mm （P＜0.01）. There was no statistically significant difference in liver and kidney function indicators between the two groups before and after treatment （P＞0.05）. ConclusionThe use of modified Shugan Dingji Decoction is a protective factor for patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation， which can help to reduce the recurrence and progression of atrial fibrillation. Long duration of illness， concomitant hypertension， and enlarged left atrial diameter are risk factors for patients to experience endpoint events.

Development and validation of a CT-based radiomics model for differentiating pneumonia-like primary pulmonary lymphoma from infectious pneumonia: A multicenter study / 中华医学杂志(英文版)

BACKGROUND@#Pneumonia-like primary pulmonary lymphoma (PPL) was commonly misdiagnosed as infectious pneumonia, leading to delayed treatment. The purpose of this study was to establish a computed tomography (CT)-based radiomics model to differentiate pneumonia-like PPL from infectious pneumonia.@*METHODS@#In this retrospective study, 79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were enrolled. Patients from center 1 to center 7 were assigned to the training or validation cohort, and the remaining patients from other centers were used as the external test cohort. Radiomics features were extracted from CT images. A three-step procedure was applied for radiomics feature selection and radiomics signature building, including the inter- and intra-class correlation coefficients (ICCs), a one-way analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model. Two radiologists reviewed the CT images for the external test set. Performance of the radiomics model, clinical factor model, and each radiologist were assessed by receiver operating characteristic, and area under the curve (AUC) was compared.@*RESULTS@#A total of 144 patients (44 with pneumonia-like PPL and 100 infectious pneumonia) were in the training cohort, 38 patients (12 with pneumonia-like PPL and 26 infectious pneumonia) were in the validation cohort, and 73 patients (23 with pneumonia-like PPL and 50 infectious pneumonia) were in the external test cohort. Twenty-three radiomics features were selected to build the radiomics model, which yielded AUCs of 0.95 (95% confidence interval [CI]: 0.94-0.99), 0.93 (95% CI: 0.85-0.98), and 0.94 (95% CI: 0.87-0.99) in the training, validation, and external test cohort, respectively. The AUCs for the two readers and clinical factor model were 0.74 (95% CI: 0.63-0.83), 0.72 (95% CI: 0.62-0.82), and 0.73 (95% CI: 0.62-0.84) in the external test cohort, respectively. The radiomics model outperformed both the readers' interpretation and clinical factor model ( P <0.05).@*CONCLUSIONS@#The CT-based radiomics model may provide an effective and non-invasive tool to differentiate pneumonia-like PPL from infectious pneumonia, which might provide assistance for clinicians in tailoring precise therapy.

Analysis of Animal Models of Cervical Spondylotic Radiculopathy Based on Characteristics of Clinical Symptoms of Chinese and Western Medicine / 中国实验方剂学杂志

With the acceleration of social rhythm， the progress of science and technology， and the increase of the number of phubbers， the incidence of cervical degenerative diseases is also increasing year by year. Cervical spondylotic radiculopathy（CSR）， as one of the diseases induced by cervical degeneration， has seriously affected people's quality of life and physical and mental health. Traditional Chinese medicine（TCM） is effective in the treatment of CSR， but the theoretical and basic experimental evidence is not sufficient， and the current formulation standard of animal model is not unified. Therefore， based on the clinical guidelines of Chinese and Western medicine for CSR and the characteristics of the disease and syndrome， the author systematically summarized and analyzed the existing animal models， and found that the existing models of microvascular clamp nerve root compression method had a poor agreement with the the Chinese and Western medical guidelines， while the modeling methods of spinal canal insertion， autologous bone insertion compression， stainless steel column compression， and fixed frame cervical degeneration reflected a high degree of agreement in the Western medical guidelines. However， the Chinese medical diagnostic criteria were poorly matched. This indicates that the existing animal models of this disease show few TCM syndrome elements， and lack information collection and evaluation in animal behavioral evaluation similar to the four diagnoses of TCM. In conclusion， this paper aims to systematically evaluate the current status of animal model establishment of CSR based on the concept of combination of disease and syndrome， so as to provide a theoretical basis for the model establishment of CSR that is more consistent with clinical characteristics and symptoms of Chinese and Western medicine.

Content determination of 5-HMF in glucosamine hydrochloride tablets and formation kinetics study / 中国药房

OBJECTIVE To establish the method for the content determination of 5-hydroxymethylfurfural （5-HMF） in glucosamine hydrochloride tablets， and to analyze its regularity and influential factors. METHODS Quantitative analysis of 5-HMF was performed using high-performance liquid chromatography. The analysis was conducted on Shim-pack GIST C18-AQ column with mobile phase consisted of 0.1% phosphoric acid solution-methanol （90∶10， V/V） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃， and detection wavelength was 284 nm. The injection volume was 20 μL. Reaction kinetics test of different temperatures was adopted to analyze the relationship of 5-HMF content with reaction temperature and reaction time， and utilized to build its formation kinetic model. RESULTS The linger range of 5-HMF was 0.057-5.698 μg/mL （r＝0.999 9）. The limits of detection and quantitation were 5.70 and 17.09 ng/mL； RSDs of precision， repeatability and stability （24 h） tests were all lower than 1.0% （n＝6）. The average recoveries ranged from 99.38% to 99.73%（RSD＝0.53%， n＝9）. The contents of the 5-HMF in 8 batches of samples ranged 4.10-35.13 μg/g. Results of data fitting in reaction kinetics test showed that the higher reaction temperature and the longer reaction time， the higher 5-HMF content in the sample. At 50， 60， 70 and 80 ℃ ， the relationship between the content of 5-HMF and the reaction time was linear， in accordance with a zero-order kinetic model. The reaction rate constants were 6.789， 7.715， 8.815 and 11.430， respectively. CONCLUSIONS The established method has strong specificity， high sensitivity， and good accuracy； the reaction temperature and reaction time are important influential factors for the formation of 5-HMF in glucosamine hydrochloride tables. The change rule of its content conforms to the zero-order kinetic model.

PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Comparative study of surgical effects on patients with mixed deafness and otosclerosis with different air bone conduction differences / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the surgical efficacy of patients with mixed hearing loss and otosclerosis with different air bone gap (ABG) before surgery, and to provide reference for the prognosis evaluation of otosclerosis surgery. Methods: The clinical data of 108 cases(116 ears) of otosclerosis who had undergone stapes fenestration technique artificial stapes implantation in Xiangya Hospital of Central South University from November 2013 to May 2020 and had mixed hearing loss before surgery were collected, including 71 women(76 ears)and 37 men (40 ears), with an average age of 38.5 years. According to preoperative pure tone audiometry ABG, they were divided into three groups: group S, 15 dB≤ABG<31 dB, a total of 39 ears; group M, 31 dB≤ABG<46 dB, a total of 58 ears; and group L, ABG≥46 dB, 19 ears in total. The hearing outcomes of three groups of patients at 6-12 months after surgery were compared and analyzed using SPSS 24.0 statistical software. Results: A total of 3 patients (group S: 2 cases; group L: 1 case) experienced severe sensorineural hearing loss after surgery and were not included in the statistical analysis. After surgery, the pure tone hearing threshold of patients with otosclerosis in each group was significantly improved compared to before surgery, with an average air conduction threshold improvement of(21.6±13.4) dB. The difference between before and after surgery was statistically significant(t=17.13, P<0.01). The average bone conduction threshold improved by(3.7±7.6) dB, and the difference was statistically significant before and after surgery(t=5.20, P<0.01). The postoperative ABG was(18.3±9.3) dB, which was significantly reduced compared to preoperative(36.2±8.6)dB. Among the three groups of patients, the L group had the highest improvement in air conduction threshold[(29.9±10.8)dB], while the S group had the lowest improvement[(15.7±11.4)dB]. There was no statistically significant difference in post operative pure tone hearing thresholds between the three groups(P>0.05). The postoperative ABG in group S was the smallest[(16.5±9.0)dB], while in group L, the postoperative ABG was the largest[(20.5±10.0)dB]. Compared with group S, group M and group L still had a large residual ABG at 2 000 Hz after surgery. The bone conduction threshold of both S and M groups improved to some extent after surgery compared to before (P<0.01). Conclusions: Surgery can benefit patients with mixed hearing loss and otosclerosis with different preoperative ABG. Patients with small preoperative ABG have better surgical results and ideal ABG closure at all frequencies after surgery. Patients with large preoperative ABG can significantly increase the gas conduction threshold during surgery, but certain frequencies of ABG may still be left behind after surgery. The improvement effect of surgery on bone conduction threshold is not significant. Patients should be informed of treatment methods such as hearing aids based on their actual situation for selection.

Radiomics-based prediction of microsatellite instability in stage Ⅱ and Ⅲ rectal cancer patients based on T2WI MRI and diffusion-weighted imaging / 中华外科杂志

Objective: To examine the radiomics model based on high-resolution T2WI and diffusion weighted imaging (DWI) in predicting microsatellite stability in patients with stage Ⅱ and Ⅲ rectal cancer. Methods: From February 2016 to October 2020, 175 patients with stage Ⅱ and Ⅲ rectal cancer who met the inclusion criteria were retrospectively collected. There were 119 males and 56 females, aged (63.9±9.4) years (range: 37 to 85 years), including 152 patients with microsatellite stability and 23 patients with microsatellite instability. All patients were randomly divided into the training group (n=123) and the validation group (n=52) with a ratio of 7∶3. The region of interest was labeled on the T2WI and DWI images of each patient using the ITK-SNAP software, and PyRadiomics was used to extract seven kinds of radiomics features. After removing redundant features and normalizing features, the least absolute shrinkage and selection operation were used for feature selection. One clinical model, three radiomics models and one clinical-radiomics model were constructed in the training group based on a support vector machine. The area under receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were used to evaluate the performance of the models in the verification group. Results: Three clinical features (age, degree of tumor differentiation, and distance from the lower edge of the tumor to the anal edge) and six radiomics features (two DWI-related features and four T2WI-related features) most related to microsatellite status of rectal cancer patients were selected. The AUC of the clinical-radiomics model in the training group was 0.95. In the validation group, the AUC was 0.81, better than the clinical model (0.68, Z=0.71, P=0.04), and equivalent to the T2WI+DWI model (0.82, Z=0.21, P=0.83). Conclusions: Radiomic features based on preoperative T2WI and DWI were related to microsatellite stability in patients with stage Ⅱ and Ⅲ rectal cancer and showed a high classification efficiency. The model based on the features provided a noninvasive and convenient tool for preoperative determination of microsatellite stability in rectal cancer patients.

Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Correlation analysis of retinal nerve fiber layer and macular retinal thickness in children with anisometropic amblyopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes and correlation of retinal nerve fiber layer(RNFL)and macular retinal thickness in children with anisometropic amblyopia.METHODS: A total of 159 cases(159 eyes)children with anisometropic amblyopia treated in our ophthalmology department from October 2020 to June 2021 were selected as the study group, and 159 cases(159 eyes)children with normal vision who examined in the ophthalmology department of our hospital in the same period and age group were selected as the control group. The study group received traditional comprehensive training combined with 4D visual training for amblyopia based on refractive correction and covering of healthy eyes. The RNFL and macular retinal thickness before and after treatment between the study group and the control group was compared, and the correlation between RNFL and macular retinal thickness before treatment in the study group was analyzed.RESULTS: The RNFL thickness of average, upper, lower, nasal and temporal in the study group before and after 3mo of treatment was higher than those of the control group, and the RNFL thickness of average, upper, lower, nasal and temporal before treatment in the study group was higher than those after 3mo of treatment(P&#x0026;#x003C;0.05). The average, inferior, nasal, temporal, nasal, and central retinal thickness of the outer ring of the macular area in the study group before treatment were higher than those in the same group after 3mo of treatment and the control group(P&#x0026;#x003C;0.05). Before treatment, there was a negative correlation between the thickness of the upper RNFL in the study group and the retinal thickness in the central macular area(r=-0.330, P&#x0026;#x003C;0.05), the thickness of the lower and nasal RNFL was positively correlated with the thickness of the temporal retina in the outer and inner rings of the macular area(all P&#x0026;#x003C;0.05), while the thickness of temporal RNFL was negatively correlated with the thickness of the nasal and temporal retina outside the macular area(r=-0.414, -0.462, all P&#x0026;#x003C;0.05).CONCLUSION: The changes in RNFL and macular retinal thickness in children with anisometropic amblyopia can hinder normal retinal development, and there is a certain correlation between RNFL and macular retinal thickness.

Diagnostic method and value of echocardiography for screening right patent ductus arteriosus in infants / 中华超声影像学杂志

Objective:To investigate the diagnostic method and value of echocardiography in screening right patent ductus arteriosus(PDA) of infants.Methods:This was a prospective study.Thirty-one infants with right PDA diagnosed by ultrasound and confirmed by prenatal ultrasonography, electronic computed tomography angiography, angiocardiography and/or surgery in Hebei Children′s Hospital from April 2014 to May 2022 were collected as research subjects, and the association of right ductus arteriosus with aortic arch anomalies and complex cardiac malformations were summarized. The diagnostic method and value of ultrasonic screening were summed up.Results:Of the 31 cases, 30 cases were correctly diagnosed by ultrasound and 1 case was misdiagnosed, who was a left aortic arch descending to the right, a crossover variation of the right and left pulmonary arteries, and a rightward displacement of the ductus arteriosus. Among these cases diagnosed correctly, 27 cases (including 24 cases with right aortic arch and 3 cases with left aortic arch) presented that ductus arteriosus was open and its ostium of pulmonary artery end was located in the proximal right pulmonary artery in views of parasternal short-axis view of great vessels at cardiac base with the combination of two dimensions and color Doppler flow imaging. Other 3 cases of right aortic arch were all single ventricle with transposition of the great artery. Due to the parallel relationship of the two great arteries, the standard parasternal short-axis view of great vessels could not be obtained, and the right ductus arteriosus was found in the high parasternal views.In all of the 27 cases with right aortic arch and right ductus arteriosus, high parasternal views showed that one end of the ductus arteriosus was connected to the right aortic arch isthmus and the other end was connected to the right pulmonary artery. In all of the 3 cases with left aortic arch and right ductus arteriosus, the high parasternal views showed that one end of the ductus arteriosus was connected to the right subclavian artery and the other end was connected to the right pulmonary artery. Among the 27 cases with right aortic arch, 16 cases were accompanied with mirror image branches, 9 cases of which had complex cardiac malformations; 10 cases were associated with aberrant left subclavian artery, 1 case of which had complex cardiac malformations; 1 case was with isolated left subclavian artery, and without complex cardiac malformations. All 3 cases of left aortic arch were accompanied with isolated right subclavian artery and none of them were associated with complex cardiac malformations. Clinical outcomes of 30 cases with right PDA: 14 cases underwent ductus arteriosus ligation due to thick ductus or other heart malformations. In other 16 cases, 4 cases were closed spontaneously, 9 cases had persistent small ductus arteriosus, and 3 cases were lost to follow-up.Conclusions:Right ductus arteriosus is mostly related to the right aortic arch, and those with mirror image branches are prone to complex cardiac malformations; cases of left aortic arch with right ductus arteriosus are tend to accompany isolated right subclavian artery. Ultrasound has an important application in the screening and diagnosis of right PDA.

Application of the sternocleidomastoid intermuscular approach in unilateral parathyroid surgery / 中华内分泌外科杂志

Objective:To investigate the feasibility and advantages of unilateral primary hyperparathyroidism (PHPT) treated by transthyretal interosseous muscle approach surgery.Methods:Clinical data of 7 patients with unilateral PHPT treated by interstitial sternocleidomastoid muscle approach from Jan. 2021 to Feb. 2022 in the thyroid surgery of China-Japan Union Hospital of Jilin University were retrospectively analyzed, including preoperative blood calcium concentration, operation time, incision length, intraoperative parathyroid hormone (PTH) , blood calcium concentration and PTH value in the first month after surgery, abnormal sensation of the skin in the anterior cervical area, etc. The feasibility and advantages of interstitial sternocleidomastoid muscle approach surgery for unilateral PHPT were analyzed.Results:All 7 patients with unilateral PHPT were operated successfully. The PTH was 17.2-63.3 pg/ml on recheck 1 month after surgery, which were all within the normal range. The time from skin opening to resection of the diseased parathyroid gland was 20-35 min, and the length of the surgical incision was 3-4 cm. all patients were given intravenous and oral calcium therapy after surgery, and the blood calcium and PTH levels were within the normal range at 3-12 months of follow-up; the incision recovered well, and there was no significant sensory and functional abnormalities in the anterior neck area.Conclusion:The treatment of unilateral PHPT through the sternocleidomastoid interosseous approach can ensure the safety and efficacy of the operation while better protecting the sensory and motor functions of the anterior cervical region and improving the aesthetics of the surgical incision.

Research Progress in Valve-sparing Aortic Root Replacement / 中山大学学报(医学科学版)

With continuous improvements in surgical techniques， medical engineering and material science， root replacement with composite valve graft （CVG） or Bentall procedure has become the standard procedure for aortic root lesions. As an alternative to the Bentall procedure， valve-sparing aortic root replacement （VSRR） avoids the complications associated with lifelong anticoagulation and mechanical valves； reduces the incidence of thromboembolic and bleeding events； and its favorable haemodynamics and potentially lower risk of endocarditis ensure durable postoperative aortic valve function and a much better quality of patient survival. This article reviews the indications for root replacement with preservation of the aortic valve， the key points of the standardized technique and its long-term results in different patients.

Research progress on use of common packaging forms of injections / 药学实践杂志

Objective To provide theoretical reference and practical basis for accurately choosing the suitable packaging forms for different Injections. Methods Based on the raw materials in the common packaging forms of injections, the research and application progress on different packaging forms for injections were reviewed by analyzing the characteristics and technical requirements of different packaging forms, and the current registration information of pharmaceutical packaging materials in the Center for Drug Evaluation, NMPA were introduced. Results For preparations with small single-dose and low-cost, the ampoules or injection vials could be chosen. Powder injections are usually packaged in injection vials. For rescue medicines and valuable medicines, the pre-filled syringes could be chosen. For chronic disease treatment drugs (such as insulin) that require long-term injection, or some injections for emergency use, a pen-type syringe package that patients can inject themselves could be used. Neutral glass packaging or plastic packaging should be used for some acidic or alkaline. Conclusion The drug manufacturers should comprehensively consider the physicochemical properties of drugs, the performance of packaging raw materials, compatibility test results, price-cost, and convenience in carrying and use when choosing the appropriate packaging form to ensure the quality, safety, and effectivity of drugs.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Gestational dexamethasone exposure impacts hippocampal excitatory synaptic transmission and learning and memory function with transgenerational effects

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

A brief discussion on the inspiration and thinking of the Metaverse concept to promote the innovative development of intelligent medicine in China / 中华外科杂志

Created by digital technology,the Metaverse is a digital platform where the digital virtual world and the actual real world can coexist to some extent. Based on the integration of Metaverse and medical science,this article describes the great development of intelligent medicine in the fields of medical practice,medical education and medical research,especially in the field of surgery. First,the technical source of the Metaverse concept in the field of intelligent medicine can be traced back to technology to generate actual digital data sets from human anatomy. Second,the successful industrial practice of Metaverse in the field of intelligent medicine conforms to the authentic and credible fundamental purpose of "taking people as the first priority and serving people"， that is， "virtual" must be based on "actual" for "actual".

A scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase receiving initial imatinib therapy / 中华血液学杂志

Objective: To develop a scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving initial imatinib therapy. Methods: Data from consecutive adults with newly diagnosed CML-CP treated by initial imatinib was interrogated and subjects were distributed randomly into training and validation cohort, in a ratio of 2∶1. Fine-gray models were applied in the training cohort to identify co-variates of predictive value for major molecular response (MMR) and MR4. A predictive system was built using significant co-variates. The predictive system was then tested in the validation cohort and the area under the receiver-operator characteristic curve (AUROC) was used to estimate accuracy of the predictive system. Results: 1 364 CML-CP subjects receiving initial imatinib were included in this study. Subjects were distributed randomly into training cohort (n=909) and validation cohort (n=455) . In the training cohort, the male gender, European Treatment and Outcome Study for CML (EUTOS) Long-Term Survival (ELTS) intermediate-risk, ELTS high-risk, high WBC (≥130×10(9)/L or 120×10(9)/L, MMR or MR4) and low HGB (<110 g/L) at diagnosis were significantly related with poor molecular responses and were given points based on their regression coefficients. For MMR, male gender, ELTS intermediate-risk and low HGB (<110 g/L) were given 1 point; ELTS high-risk and high WBC (≥130×10(9)/L) , 2 points. For MR4, male gender was given 1 point; ELTS intermediate-risk and low HGB (<110 g/L) were given 2 points; high WBC (≥120×10(9)/L) , 3 points; ELTS high-risk, 4 points. We divided all subjects into 3 risk subgroups according to the predictive system above. Cumulative incidence of achieving MMR and MR4 in 3 risk subgroups was significantly different in both training and validation cohort (all P values <0.001) . In the training and validation cohorts, the time-dependent AUROC ranges of MMR and MR4 predictive systems were 0.70-0.84 and 0.64-0.81, respectively. Conclusions: A scoring system combining gender, WBC, HGB level and ELTS risk was built to predict MMR and MR4 in CML-CP patients receiving initial imatinib therapy. This system had good discrimination and accuracy, which could help phsicians optimize the selsction of initial TKI-therapy.

Circulating Exosomal LncRNAs as Novel Diagnostic Predictors of Severity and Sites of White Matter Hyperintensities / 生物医学与环境科学（英文）

OBJECTIVE@#Exosomal long noncoding RNAs (lncRNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lncRNAs in white matter hyperintensities (WMH).@*METHODS@#We used high-throughput sequencing to determine the differential expression (DE) profiles of lncRNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using qRT-PCR. The diagnostic potential of candidate exosomal lncRNAs was proven by binary logistic analysis and receiver operating characteristic (ROC) curves. The diagnostic value of DE exo-lncRNAs was determined by the area under the curve (AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lncRNAs in the subgroup was evaluated.@*RESULTS@#In our results, four DE exo-lncRNAs were identified, and ROC curve analysis revealed that exo-lnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities.@*CONCLUSION@#Plasma exosomal lncRNAs have potential diagnostic value in WMH. Moreover, exo-lnc_011797 is considered to be a predictor of the severity and location of WMH.