Exogenous neuritin restores auditory following cochlear spiral ganglion neuron denervation of gerbils.

Spiral ganglion neurons (SGNs) transmit sound signals received by hair cells to the auditory center to produce hearing. The quantity and function are important for maintaining normal hearing function. Limited by the regenerative capacity, SGNs are unable to regenerate spontaneously after injury. Various neurotrophic factors play an important role in the regeneration process. Neuritin is a neurite growth factor that plays an important role in neural plasticity and nerve injury repair. In this study, we used bioinformatics analysis to show that neuritin was negatively correlated with cochlear damage. Then, we aimed to establish a cochlear spiral ganglion-specific sensorineural deafness model in gerbils using ouabain and determine the effects of exogenous neuritin protein in protecting damaged cochlear SGNs and repairing damaged auditory nerve function. The provides a new research strategy and scientific basis for the prevention and treatment of sensorineural deafness caused by the loss of SGNs. We were discovered that neuritin is expressed throughout the development of the gerbil cochlea, primarily in the SGNs and Corti regions. The expression of neuritin was negatively correlated with the sensorineural deafness induced by ouabain. In vitro and in vivo revealed that neuritin significantly maintained the number and arrangement of SGNs and nerve fibers in the damaged cochlea and effectively protected the high-frequency listening function of gerbils.

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<MMC group<biological amniotic membrane group<blank control group(all P<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.

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.

Retrospective comparative study of the efficacy of JAK inhibitor (tofacitinib) in the treatment of systemic sclerosis-associated interstitial lung disease.

The oral Janus kinases inhibitor (JAKi) has improved the management of skin manifestations in systemic sclerosis (SSc), and our study aimed to explore the efficacy of non-selective JAKi tofacitinib in ameliorating interstitial lung disease (ILD) in the patients with SSc. The hospitalization data of the SSc-ILD patients from April 2019 to April 2021 were collected, and the changes of pulmonary function and the radiological findings in pulmonary high-resolution CT (HRCT) from the 9 patients who received tofacitinib for at least 6 months and a matched group of 35 SSc-ILD patients treated with conventional immunosuppressants or glucocorticoids, were compared and analyzed. There were no significant differences in demographic data and clinical characteristics between the tofacitinib-treated group (tofa-group) and the matched group. However, in the tofa-group, the changes in serum lactate dehydrogenase (LDH) concentration and serum interleukin-6 levels were significantly lower than those in the matched group. Moreover, the tofa-group showed amelioration in decreased diffusing capacity of the lung for carbon monoxide (DLCO) (62.05 ± 9.47 vs. 66.61 ± 12.39, p = 0.046), reductions in ground-glass attenuation involvement (1.00 ± 0.86 vs. 0.33 ± 0.50, p = 0.024) and irregular pleural thickening (1.33 ± 0.50 vs. 0.67 ± 0.51, p = 0.004) in pulmonary HRCTs, alleviated modified Rodnan skin score (mRSS) of skin sclerosis (9.22 ± 3.81 vs. 7.11 ± 3.92, p = 0.048), and reduced HRCT scores of pulmonary fibrosis (15.00 ± 3.87 vs. 12.66 ± 4.92, p = 0.009). Logistic regression analysis showed that the involvement of ground-glass attenuation (OR 11.43) and the add-on therapy of tofacitinib (OR 9.98) were the relevant factors in the amelioration of HRCT. Our results indicate that the use of JAKi (tofacitinib) may be relevant to significant improvement of the sclerosis and early radiological abnormalities in SSc-ILD patients. Further studies are needed to confirm these findings and to explore its efficacy more precisely. Key Points • The currently available therapies for SSc-ILD have limited therapeutic benefits. • The add-on therapy of the oral JAK inhibitor is available in the real world. • The tofacitinib was promising in the improvement of the sclerosis and early radiological abnormalities in SSc-ILD patients.

Transcutaneous auricular vagus nerve stimulation would be an alternative to implantable cervical vagus nerve stimulation in some situation.

Implantable cervical vagus nerve stimulation (iVNS) is a representative and promising neuromodulation. However, the invasive nature restricts its application. Traditional auricular acupuncture treatment has a long history. The auricular branch of the vagus nerve (ABVN) is a branch on the surface of the ear. Some studies demonstrates that transcutaneous auricular vagus nerve stimulation (taVNS) would achieve similar effects as iVNS. TaVNS and iVNS share a common anatomical basis and acting mechanism. In this article, we made a comparison between iVNS and taVNS in indications and efficacy. The recent studies have revealed similar clinical efficacy of taVNS, taVNS would expand the indication of iVNS. High-quality clinical evidences are needed before taVNS become be an alternative of iVNS.

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.

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.

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.

Correlation of serum vitamin D with semen parameters and sex hormone levels in men / 现代泌尿外科杂志

【Objective】 To explore the correlation between serum vitamin D level and male semen parameters and serum sex hormones. 【Methods】 A total of 56 men who received assisted reproductive treatment in our hospital during Oct.2020 and Oct.2021 were included in the infertility group, and 56 male patients with previous reproductive histories who were treated due to other diseases during the same period were enrolled as the control group. The sperm motility and concentration were assessed using a computer assisted semen analysis system (CASA). The normal sperm morphology rate was evaluated with sperm morphological staining. Sperm DNA fragmentation index (DFI) was detected with chromatin diffusion method to evaluate sperm chromatin integrity. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and 25-hydroxyvitamin D [25(OH)D] were detected with ELISA. The correlation between serum 25(OH)D level and semen parameters and sex hormones was analyzed. 【Results】 Serum 25(OH)D level was significantly higher in the control group than in the infertile group (P=0.002). It was positively correlated with semen parameters, including sperm motility (r=0.483, P<0.001), sperm count (r=0.216, P=0.019), and testosterone level (r=0.210, P=0.025). There was no significant correlation between serum 25(OH)D concentration and sperm morphology, LH and FSH levels. 【Conclusion】 Serum 25(OH)D is significantly correlated with and affects total sperm count, sperm motilityand serum testosterone, thus playing a role in male reproduction. The specific mechanism needs further study.

Effects of Modified Sanhuang Powder （加味三黄散） Combined with Cold Compression on Swelling and Pain after Knee Arthroscopy： A Retrospective Cohort Study / 中医杂志

ObjectiveTo compare the effects of topical application of Modified Sanhuang Powder （加味三黄散， MSP） combined with cold compression versus cold compression alone on swelling and pain after knee arthroscopy through a retrospective cohort study. MethodsMedical records of 134 patients with knee arthroscopy-induced knee swelling and pain were divided into non-exposure group （51 cases） and exposure group （83 cases） based on whether they used MSP for external application after surgery. The non-exposure group received simple cold compression therapy in addition to functional exercise and routine treatment after surgery， while the exposure group received topical MSP on the basis of what were given in the non-exposure group. The Visual Analog Scale （VAS） scores were compared between the two groups before and 7 days after treatment， and knee swelling measurements were taken before and 3， 5， and 7 days after treatment. The clinical effective rate was compared between the two groups. ResultsThe VAS scores in both groups were lower after treatment （P＜0.05）， and the exposure group had lower scores than the non-exposure group （P＜0.05）. On the 3rd， 5th， and 7th days of treatment， the scores on swelling at 2 cm above the superior pole of the patella， at the midline of the patella， and 5 cm below the inferior pole of the patella significantly decreased after treatment in both groups （P＜0.05）， and the exposure group had lower scores than the non-exposure group （P＜0.05）. The total clinical effective rate in the exposure group was 91.56% （76/83）， which was higher than 78.43% （40/51） in the non-exposure group （P＜0.05）. ConclusionTopical application of MSP combined with cold compression is effective in relieving postoperative swelling and pain after knee arthroscopy and is superior to cold compress alone.

Effects of metformin hydrochloride tablets on clinical efficacy and number of dominant follicles in polycystic ovary syndrome / 药学实践杂志

Objective To explore the effect of metformin hydrochloride tablets on the clinical efficacy, number of dominant follicles and ovarian volume of polycystic ovary syndrome. Methods 150 patients diagnosed with polycystic ovary syndrome who were diagnosed and treated in our hospital from January 2019 to March 2021 were selected .The patients were divided into observation group and control group by random number table. The control group was treated with letrozole + gonadotropin, and the observation group was treated with letrozole + gonadotropin + hydrochloric acid + Metformin tablets. The clinical efficacy, endometrial thickness, number of high-quality follicles, sex hormone levels, blood lipid levels, and adverse reactions were compared between the two groups. Results ① The effective rate of treatment in the observation group was 90.67%, which was significantly higher than that in the control group, 78.67% (P<0.05). ② After treatment, the endometrial thickness of the observation group was lower than that of the control group, and the number of high-quality follicles was more than that of the control group(P<0.05). ③ After treatment, the levels of Luteinizing Hormone-LH, Follicle Stimulating Hormone-FSH and Testosterone (T) in the observation group were lower than those in the control group (P<0.05). ④ After treatment, the total cholesterol (TC) and triglyceride (TG) in the observation group were lower than those in the control group (P<0.05). ⑤ The incidence of adverse reactions in the observation group was 8.00%, which was significantly lower than 20.00% in the control group (P<0.05). Conclusion Letrozole + gonadotropin + metformin hydrochloride tablets could significantly improve the sex hormone and blood lipid levels in patients with polycystic ovary syndrome, relieve the symptoms of the patients, and improve their uterine condition, which had a good clinical effect.

Assessing Abdominal Aortic Aneurysm Progression by Using Perivascular Adipose Tissue Attenuation on Computed Tomography Angiography

Objective@#Recent studies have highlighted the active and potential role of perivascular adipose tissue (PVAT) in atherosclerosis and aneurysm progression, respectively. This study explored the link between PVAT attenuation and abdominal aortic aneurysm (AAA) progression using computed tomography angiography (CTA). @*Materials and Methods@#This multicenter retrospective study analyzed patients with AAA who underwent CTA at baseline and follow-up between March 2015 and July 2022. The following parameters were obtained: maximum diameter and total volume of the AAA, presence or absence of intraluminal thrombus (ILT), maximum diameter and volume of the ILT, and PVAT attenuation of the aortic aneurysm at baseline CTA. PVAT attenuation was divided into high (> -73.4 Hounsfield units [HU]) and low (≤ -73.4 HU). Patients who had or did not have AAA progression during the follow-up, defined as an increase in the aneurysm volume > 10 mL from baseline, were identified. Kaplan–Meier and multivariable Cox regression analyses were used to investigate the association between PVAT attenuation and AAA progression. @*Results@#Our study included 167 participants (148 males; median age: 70.0 years; interquartile range: 63.0–76.0 years), of which 145 (86.8%) were diagnosed with AAA accompanied by ILT. Over a median period of 11.3 months (range: 6.0–85.0 months), AAA progression was observed in 67 patients (40.1%). Multivariable Cox regression analysis indicated that high baseline PVAT attenuation (adjusted hazard ratio [aHR] = 2.23; 95% confidence interval [CI], 1.16–4.32; P = 0.017) was independently associated with AAA progression. This association was demonstrated within the patients of AAA with ILT subcohort, where a high baseline PVAT attenuation (aHR = 2.23; 95% CI, 1.08–4.60; P = 0.030) was consistently independently associated with AAA progression. @*Conclusion@#Elevated PVAT attenuation is independently associated with AAA progression, including patients of AAA with ILT, suggesting the potential of PVAT attenuation as a predictive imaging marker for AAA expansion.

A Novel EYA1 Mutation Causing Alternative RNA Splicing in a Chinese Family With Branchio-Oto Syndrome: Implications for Molecular Diagnosis and Clinical Application

Objectives@#. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. @*Methods@#. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. @*Results@#. A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. @*Conclusion@#. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

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.