Building methodological consensus to ensure rigor and reproducibility in zebrafish fertility research.

The summary included in the text: Zebrafish are an increasingly popular model for studying the genetic and environmental factors that shape male and female fertility; however, the field currently lacks a standardized approach to fertility assessment. The current lack of consensus makes comparisons across studies more challenging and is an obstacle to reproducibility in the fields of reproductive biology and toxicology. Here, we review the diversity of spawning approaches used in zebrafish reproductive toxicology research to asses fertility and provide evidence that spawning parameters can result in meaningful differences in egg production and spawning success.

[Comparison of efficacy between short-term personalized vestibular rehabilitation supervised by special personnel and fixed vestibular rehabilitation on recurrent peripheral vertigo].

Objective: To explore the efficacy of short-term personalized vestibular rehabilitation supervised by special personnel (ST-PVR) versus fixed vestibular rehabilitation (FVR) on decompensated recurrent peripheral vertigo. Methods: A randomized controlled trial was carried out. Patients diagnosed with decompensated recurrent vertigo in the clinic of Eye & ENT Hospital, Fudan University from January to December 2018 were randomly allocated into FVR and ST-PVR groups via computer-generated randomization. The FVR group received fixed scheme involving gaze stabilization exercises, habituation exercises, balance and gait training, while the ST-PVR group received individualized training programs based on symptoms and vestibular function examination results, with adjustments made according to the progress of recovery. Patient symptoms and vestibular function improvement were assessed using the dizziness handicap inventory (DHI), activities-specific balance confidence (ABC), self-rating anxiety scale (SAS), caloric test, and sensory organization test (SOT) at 2, 4, and 8 weeks of treatment. Results: A total of 44 patients were included, including 16 males and 28 females, with an average age of (50.6±13.5) years. There were 21 cases in the FVR group and 23 cases in the ST-PVR group. In the ST-PVR group, DHI score (49.5±26.8 vs 61.3±21.4, P=0.046) and SAS score (39.1±7.8 vs 44.3±6.6, P=0.021) significantly improved after 2 weeks of treatment, while significant improvement occurred only after 8 weeks of treatment in the FVR group (DHI score: 28.1±15.9 vs 53.1±18.5, P=0.001; SAS score: 35.3±6.7 vs 43.1±8.4, P=0.010). There was no significant change of ABC score in the FVR group after 8 weeks of treatment (86.5±12.9 vs 83.4±18.1, P=0.373), while a significant improvement was observed in the ST-PVR group after 4 weeks of treatment (83.6±15.2 vs 78.4±15.1, P=0.015). The caloric test results showed that after 8 weeks of treatment, the proportion of patients with unilateral weakness<25% increased in both groups [FVR group: 57.1% (12/21) vs 9.5% (2/21), P=0.001; ST-PVR group: 52.2% (12/23) vs 17.4% (4/23), P=0.014]. In the ST-PVR group, the proportion of patients with dominant preference≤25% significantly increased [91.3% (21/23) vs 60.9% (14/23), P=0.016], while there was no significant change in the FVR group [61.9 (13/21) vs 57.1% (12/21), P=0.500]. The proportion of patients with SOT score≥70 in the ST-PVR group increased significantly after 2 weeks of treatment [69.6% (16/23) vs 30.4% (7/23), P=0.009], while the FVR group showed a significant increase only after 8 weeks of treatment [81.0% (17/21) vs 42.9% (9/21), P=0.012]. Conclusion: Both FVR and ST-PVR effectively promote vestibular compensation by improving objective vestibular functions and relieving subjective symptoms and anxiety of the patients with decompensation recurrent vertigo, while ST-PVR might shorten the recovery time and increase balance confidence.

Cardiac MRI for clinical dilated cardiomyopathy: Improved diagnostic power via combined T1, T2, and ECV.

INTRODUCTION: Early diagnosis of patients with dilated cardiomyopathy (DCM) remains challenging. Cardiac MR can correlate myocardial changes with their pathological basis. There have been some previous studies on the effect of T1 mapping in DCM, but there is limited data on the incremental value of T2 mapping for DCM in routine clinical practice. This study will examine whether the combination of MRI T1 and T2 mapping offers greater advantages in the diagnosis of DCM. METHODS: The study included 28 patients with DCM and 21 healthy controls. CMR evaluation included late gadolinium enhancement (LGE), T1 mapping, extracellular volume (ECV) fraction and T2 mapping. The DCM group was divided into LGE (+) and LGE (-) subgroups. The main modes of LGE are subendocardial, midwall, subepicardial, or transmural. T1 values, T2 values, and ECV in the 16 segments myocardial levels were measured by post-processing software. Student's t-tests or Mann-Whitney U test was used to compare between two groups, and one-way ANOVA or Kruskal-Wallis H test was used to compare between multiple groups, with p values corrected by Bonferroni. The difference was considered statistically significant at P < 0.05. ROC curve analysis was used to compare the area under the curve (AUC) of each index and its combined value, and the cut-off value, sensitivity and specificity were determined by Jordan's index. RESULTS: Mean native myocardial T1, ECV and T2 were significantly higher in the DCM group compared to controls (p ≤ 0.001, respectively). The best cut-off values for T1, T2 and ECV to discriminate DCM from controls were 1184 ms, 40.9 ms and 29.2%, respectively. The AUC of T1, ECV and T2 were 0.87, 0.89, and 0.83, respectively. The combined AUC of the three values was 0.96. CONCLUSION: Native T1 value and ECV overcome some of the limitations of LGE, and the T2 helps to understand the extent of myocardial damage. The combination of T1 and T2 mapping techniques can reveal fibrotic and oedematous changes in the early stages of DCM, providing a more comprehensive assessment of DCM and better guidance for individualised clinical management of patients. IMPLICATIONS FOR PRACTICE: We suggest that the addition of T2 mapping to the routine CMR examination of patients with suspected DCM, and the combined assessment of T1mapping and T2 mapping can provide complementary information about the disease and improve the early diagnosis of DCM.

Development and validation of a nomogram and risk stratification system to predict overall survival after surgical repair for pediatric patients with medulloblastoma based on easily accessible variables.

OBJECTIVE: This study aimed to develop and validate a nomogram and risk stratification system for the overall survival of pediatric patients with medulloblastoma after surgical repair. PATIENTS AND METHODS: In this multicenter, retrospective study, consecutive patients who underwent surgery for medulloblastoma at Shanghai Children's Medical Center and the First Affiliated Hospital of Fujian Medical University from 2010 to 2022 formed the training and external validation datasets, respectively. Univariable and multivariable Cox regression analyses were performed to identify variables associated with mortality in the training dataset. A nomogram prediction model was developed based on independent variables in the multivariable Cox regression analysis to predict the 1-, 3-, and 5-year overall survival. The area under receiver operating characteristic curve (AUC) and calibration curve were used to evaluate the discrimination and calibration of the nomogram. A risk stratification system based on the median risk score was also established to divide patients into two risk groups. RESULTS: In the training dataset, Cox regression analyses identified tumor size, brainstem involvement and chemotherapy as independent predictors for overall survival. The AUC of the nomogram was 0.75 at 1 year, 0. 75 at 3 years, 0.77 at 5 years in the training dataset, 0.74 at 1 year, 0.70 at 3 years, and 0.70 at 5 years in the validation dataset. The calibration curve for the probability of 1-, 3-, and 5-year survival showed good agreement between the nomogram prediction and actual observation in the training and validation datasets. The risk stratification system could perfectly classify patients into two risk groups, and the overall survival in the two groups had a good division. CONCLUSIONS: This low-cost, convenient, and noninvasive nomogram can be translated into clinical practice as a tool for risk stratification and individualized prognosis prediction for children with medulloblastoma.

[Galangin inhibits oxidized low-density lipoprotein-induced angiogenic activity in human aortic endothelial cells by downregulating lncRNA H19].

OBJECTIVE: To investigate the effects of galangin on angiogenic activity of oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs) and explore the underlying mechanisms. METHODS: HAECs incubated with 10, 20, 40, and 80 µmol/L galangin for 24 h were assessed for cell viability changes using MTT assay to determine the cytotoxicity of galangin. HAECs treated with 5 mg/mL ox-LDL and incubated with 20 and 40 µmol/L galangin for 24 h, and the cells overexpressing lncRNA H19 and incubated with 40 µmol/L galangin for 24 h were examined for lncRNA H19 level with qRT-PCR. The migration and tube formation capacity of the cells were observed using scratch assay and angiogenesis assay, and ROS levels in the cells were detected with flow cytometry. The protein expression levels of VEGFA, MMP-2 and MMP-9 in the treated cells were detected with Western blotting. RESULTS: Galangin at 10, 20, or 40 µmol/L produced no obvious toxicity (P>0.05), whereas 80 µmol/L galangin significantly inhibited the viability of HAECs (P<0.01). Treatment with ox-LDL significantly increased the expression of lncRNA H19 in HAECs. Galangin significantly lowered lncRNA H19 expression in ox-LDL-induced HAECs, suppressed cell migration, angiogenesis and ROS production level, and reduced the protein levels of VEGFA, MMP-2 and MMP-9 (P<0.01). The effects of galangin were blocked by overexpression of lncRNA H19 in the cardiomyocytes. CONCLUSION: The therapeutic effect of galangin for atherosclerosis is mediated by inhibiting lncRNA H19 expression to reduce ox-LDL-induced migration, oxidative stress, and angiogenesis of HAECs.

[Efficacy of 0.05% cyclosporine A combined with vitamin A palmitate in the treatment of meibomian gland dysfunction-related dry eye].

Objective: To evaluate the efficacy of 0.05% cyclosporine A eye drops combined with vitamin A palmitate eye gel in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: A single-center, prospective, randomized, parallel controlled trial design was used to include patients diagnosed with MGD-associated dry eye. The patients were randomly divided into three groups and administered with medications binocularly for 12 weeks. The CsA+VA group was given 0.05% cyclosporine A eye drops twice a day and vitamin A palmitate eye gel three times a day. The CsA+HA group was given 0.05% cyclosporine A eye drops twice a day and 0.1% sodium hyaluronate eye drops three times a day. The HA group was given 0.1% sodium hyaluronate eye drops 3 times a day. The OSDI score, tear meniscus height, fluorescein tear break-up time, Schirmer Ⅰ test (without anesthesia), tear film lipid layer thickness, meibomian gland morphology and function examination, and corneal fluorescein sodium staining score were evaluated at baseline, 4, 8, and 12 weeks after the initiation of the treatment, respectively. Results: A total of 120 patients with MGD-related dry eye met the enrollment criteria, but 10 patients were lost to follow-up; 110 patients were finally included for observation, including 36 patients in the CsA+VA group, 38 in the CsA+HA group and 36 in the HA group. The OSDI score, tear meniscus height, fluorescein tear break-up time and meibomian gland secretion of the 3 groups were significantly improved. At the 12th week of the treatment, the differences of the CsA+VA group [25.45±15.11, (0.30±0.13) mm, (3.72±1.40) s, (5.03±2.52) points] and the CsA+HA group [26.98±16.89, (0.27±0.10) mm, (4.34±1.76) s, (5.11±2.39) points] from the HA group [24.57±11.26, (0.24±0.06) mm, (3.18±1.11) s, (9.11±3.34) points] were statistically significant (P<0.05). Compared with the CsA+HA group [(68.39±26.66) nm], the tear film lipid layer thickness in the CsA+VA group [(72.61±23.65) nm] was significantly increased (P<0.05). In the CsA+VA group, the meibomian gland secretion characters and discharge capacity among patients with severe abnormalities [(6.28±2.59) and (5.89±2.77) points at the 12th week of treatment], moderate abnormalities [(4.27±2.02) and (4.64±2.02) points at the 12th week of treatment] and mild abnormalities [(2.80±0.84) and (2.60±0.55) points at the 12th week of treatment] were significantly different (P<0.05). Conclusion: 0.05% cyclosporine A combined with vitamin A palmitate can significantly improve the symptoms and signs of patients with MGD-related dry eye, especially the tear film lipid layer thickness and the meibomian gland secretion characters and discharge capacity in severe cases.

Comparative investigation of transport and deposition of nebulized particles in nasal airways following various middle turbinectomy.

BACKGROUND: Topical intranasal medication is required following functional endoscopic sinus surgery (FESS). The optimal particle size of transnasal nebulization aimed at the sinonasal cavities is not conclusive. The current study aims to evaluate the effect of particle size and various surgery scope of middle turbinectomy (MT) on post-full FESS drug delivery to the sinonasal cavities. METHODS: Sinonasal reconstructions were performed from post-full FESS CT scans in 6 chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Four additional models representing alternative surgery scopes of MT were established from each post-FESS reconstruction for simulation data comparison. Airflow and particle deposition of nebulized delivery were simulated via computational fluid dynamics (CFD) and validated through in vitro experiments. The optimal particle sizes reaching a deposition of at least 75% of the maximum in the targeted regions were identified. RESULTS: The drug deposition rate onto the targeted regions increased following MT, with the greatest deposition following posterior MT (P-MT). Droplets in the range of 18-26 λm reached a deposition of larger than 75% of the maximum onto the targeted regions. Drug delivery rate in the sinonasal cavities varied significantly among individuals and across different types of MT with varying surgical scopes. CONCLUSIONS: This study is the first to investigate the effect of various surgery scope on drug delivery by transnasal nebulization to the sinonasal cavities. The findings strongly affirm the vast potential of transnasal nebulization as an effective post-FESS treatment option. Moreover, it emphasizes that the drug delivery process via atomizers to the nasal cavity and paranasal sinuses is highly sensitive to the particle size.

[Sevoflurane alleviates ventilator-induced lung injury in rats by down-regulating the TRPV4/C-PLA2 signaling pathway].

OBJECTIVE: To explore the mechanism underlying the protective effect of sevoflurane against ventilator-induced lung injury (VILI). METHODS: Thirty-two SD rats were randomized into mechanical ventilation (MV) group, MV+sevoflurane group (MS group), MV+sevoflurane+transient receptor potential vanillate subtype 4 (TRPV4) agonist group (MST group) and MV+ sevoflurane + vehicle group (MSV group). Arachidonic acid (AA) in the lung tissues was quantified with ELISA. TRPV4, cytoplasmic phospholipase A2 (C-PLA2) and myosin light chain kinase (MLCK) protein expressions were detected by Western blotting. Lung injury in the rats was evaluated by assessing MLCK protein expression level, pulmonary permeability index, lung wet/dry ratio, leukocyte count in the bronchoalveolar lavage fluid (BALF), myeloperoxidase content in lung tissue, and histological score of the lungs. RESULTS: The rats in MV group showed significantly increased TRPV4 and C-PLA2 expression levels in the lung tissues with increased lung permeability and obvious lung inflammation compared with those in the other 3 groups (P < 0.05). No significant differences were found in the parameters associated with lung injuries between MS group and MSV group. Compared with those in MST group, the rats in MS group and MSV group showed significantly reduced AA production and TRPV4 and C-PLA2 expressions in the lungs (P < 0.05) with alleviated lung hyper-permeability and inflammation (P < 0.05). CONCLUSION: Sevoflurane protects against VILI in rats by down-regulating the TRPV4/C-PLA2 signaling pathway.

[Study on the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A].

Objective: To summarize the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A. Methods: In the retrospective study, a total of 1 226 clinical isolates from suspected multidrug-resistant pulmonary tuberculosis patients in Beijing TB control system from 2016 to 2021 were identified as Mycobacterium tuberculosis (MTB) strains by MPB64 antigen detection test. Rifampicin-resistant tuberculosis (RR-TB) strains were screened by the phenotypic drug susceptibility using the proportion method. The drug susceptibilities of Levofloxacin(LFX), Moxifloxacin(MFX), Bedaquiline(BDQ) and Linezolid(LZD)were detected by the phenotypic drug susceptibility with microplate method. The drug resistance rate, drug resistance level and minimum inhibitory concentration (MIC) distribution of four anti-tuberculosis drugs in group A were analyzed. We calculated the demographic distribution of RR-TB, multidrug-resistant tuberculosis(MDR-TB), pre-extensively drug resistant tuberculosis (pre-XDR-TB), extensively drug resistant tuberculosis (XDR-TB) patients and the cross resistance of LFX and MFX, then summarized the drug-resistance spectrum of BDQ-resistant and LZD-resistant strains and the treatment outcome of RR-TB patients. Measurement data were expressed as rate or composition ratio,χ2 test was used between and within groups, and P<0.05 was considered statistically significant. Results: Among the 1 226 suspected multidrug-resistant pulmonary tuberculosis patients, the detection rates of RR/MDR/pre-XDR/XDR-TB patients were 20.8%(255/1 226), 15.2%(186/1 226), 5.7%(70/1 226), 0.5%(6/1 226), respectively. There were statistically significant differences in the distribution of patients with the four types of drug resistance in terms of age and treatment history (χ2=14.95, P=0.020;χ2=15.91, P=0.001). The drug resistance rates of LFX, MFX, BDQ and LZD in RR-TB patients were 27.5% (70/255), 27.5% (70/255), 0.4% (1/255) and 2.4% (6/255), respectively. The MICs of LFX, MFX and LZD-susceptible MTB were mainly at 0.25 mg/L, and the MIC of BDQ-susceptible MTB was mainly concentrated at 0.03 mg/L. 25.1% (64/255) of the RR MTB were resistant to both LFX and MFX, and 6 strains were resistant to LFX or MFX, showing incomplete two-way cross resistance. One BDQ-resistant strain and six LZD-resistant strains were detected. The treatment success rate of RR-TB patients was 74.4% (151/203), and there were statistically significant differences in treatment outcomes between resistant and sensitive patients on the LFX-containing treatment regimen (Fisher's exact test, P=0.012). Conclusions: The prevalence of fluoroquinolones (LFX and MFX) resistance in rifampicin-resistant MTB is very serious. LFX and MFX show incomplete bidirectional cross-resistance. BDQ and LZD have the most promising future in the treatment of MDR-TB. Improve drug-resistance testing will help to further improve the success rate of treatment.

[Prevalence of comorbid depression and anxiety and effect of psychological interventions among schistosomiasis patients in China: a meta-analysis].

OBJECTIVE: To investigate the prevalence of comorbid depression and anxiety and to evaluate the effect of psychological interventions among schistosomiasis patients in China, so as to provide insights into improvements of psychological health among schistosomiasis patients. METHODS: Publications pertaining to comorbid depression and anxiety and psychological interventions among Chinese schistosomiasis patients were retrieved in electronic databases, including CNKI, Wanfang Data, PubMed, Web of Science, and Embase. The prevalence of comorbidity, psychological interventions, and scores for the Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) before and after psychological interventions among Chinese schistosomiasis patients were extracted. The prevalence of comorbid depression and anxiety was investigated among Chinese schistosomiasis patients using a meta-analysis, and the effect of psychological interventions for depression and anxiety was evaluated. RESULTS: A total of 231 publications were retrieved, and 14 publications that met the inclusion and exclusion criteria were included in the final analysis, including 2 English publications and 12 Chinese publications. Meta-analysis showed that the prevalence rates of comorbid depression and anxiety were 61% [95% confidential interval (CI): (48%, 72%)] and 64% [95% CI: (42%, 81%)] among Chinese schistosomiasis patients. Both the SDS [1.45 points, 95% CI: (1.30, 1.60) points] and SAS scores [2.21 points, 95% CI: (2.05, 2.38) points] reduced among Chinese schistosomiasis patients after psychological interventions than before psychological interventions, and the SDS [-0.47 points, 95% CI: (-6.90, -0.25) points] and SAS scores [-1.30 points, 95% CI: (-1.52, -1.09) points] reduced among Chinese schistosomiasis patients in the case group than in the control group. CONCLUSIONS: The comorbid anxiety and depression are common among Chinese schistosomiasis patients, and conventional psychological interventions facilitate the improvements of anxiety and depression among schistosomiasis patients.

[Progress of researches on Blastocystis hominis infection among patients with inflammatory bowel disease and irritable bowel syndrome].

Blastocystis is a common unicellular intestinal protozoa in humans and animals, and the most common clinical manifestations of infections include abdominal pain and diarrhea. Based on the sequence of the small-subunit ribosomal RNA (SSU rRNA) gene, 28 subtypes of B. hominis (ST1 to ST17, ST21 and ST23 to ST32) have been characterized. Previous studies have demonstrated that B. hominis infection is strongly associated with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other intestinal diseases, which threatens the health and quality of life among patients with B. hominis infection and is considered as an important public health problem. This review summarizes the progress of researches on B. hominis infection among IBD and IBS patients during the past 20 years, so as to provide insights into management of blastocystosis in China.

[The value of a nomogram for predicting the outcome of intracerebral hemorrhage based on clinical characteristics and diffusion-weighted imaging of hyperintense lesions].

Objective: To investigate the value of a nomogram predicting the outcome of intracerebral hemorrhage (ICH) based on clinical characteristics and diffusion-weighted imaging (DWI) of hyperintense lesions. Methods: A case-control study. Consecutive patients, aged 30-88(59±13) years old, with ICH were recruited at the Stroke Center of Zhengzhou People's Hospital from January 2018 to August 2021. Patients were divided into a group with DWI lesions and a group without DWI lesions depending on whether there were DWI hyperintense lesions distant from the hematoma. Prognosis was evaluated at 90 days via the modified Rankin Scale (mRS). Univariate and multivariable logistic regression models were used to identify independent predictors of a poor ICH outcome (mRS score≥4), and a nomogram model was developed. The performance of the nomogram was validated via the area under the receiver operating characteristic curve (AUC) and a calibration chart. Results: Of the 303 patients included in the study, 24.8% presented with DWI lesions; 17.5% with asymptomatic DWI lesions and 7.3% with symptomatic DWI lesions. Poor outcomes were significantly more frequent in the group with DWI lesions than in the group without DWI lesions (χ2=21.32, P<0.001). In multivariable regression analysis, age [odds ratio (OR)=1.032, 95% confidence interval (CI) 1.002-1.063, P=0.035], hematoma volume (OR=1.050, 95%CI 1.011-1.090, P=0.012), hematoma location (OR=3.839, 95%CI 1.248-11.805, P=0.019), DWI lesions (OR=3.955, 95%CI 1.906-8.206, P<0.001), and baseline NIHSS scores (OR=1.102, 95%CI 1.038-1.170, P=0.001) were independent predictors of a poor outcome. In subgroup analysis patients with asymptomatic DWI lesions had a 3-fold greater risk of a poor outcome compared to those without DWI lesions (OR=3.135, 95%CI 1.382-7.112, P=0.006), and patients with symptomatic DWI lesions had a 7-fold greater risk of a poor outcome compared to those without DWI lesions (OR=7.126, 95%CI 2.279-22.277, P=0.001). A nomogram model was established based on the independent predictors for a poor outcome. The AUC of the nomogram was 0.846 (95%CI 0.795-0.898), and a calibration chart indicated good consistency between values predicted by the nomogram and actual observed values. Conclusions: DWI lesions are an independent risk factor for a poor outcome in patients with ICH-particularly symptomatic DWI lesions. A nomogram model based on clinical characteristics and DWI lesions exhibited good efficacy when predicting the outcome of ICH.

Transient dystonia correlates with parkinsonism after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine in nonhuman primates.

Unilateral internal carotid artery 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion in non-human primates produces transient contralateral hemi-dystonia followed by stable contralateral hemi-parkinsonism; the relationship between dystonia and parkinsonism remains unclear. We hypothesized that transient dystonia severity following MPTP correlates with parkinsonism severity. In male Macaca nemestrina (n = 3) and M. fascicularis (n = 17) we administered unilateral intra-carotid MPTP, then correlated validated blinded ratings of transient peak dystonia and delayed parkinsonism. We also correlated dystonia severity with post-mortem measures of residual striatal dopamine and nigral neuron counts obtained a mean 53 ± 15 days following MPTP, after resolution of dystonia but during stable parkinsonism. Median latency to dystonia onset was 1 day, and peak severity 2.5 days after MPTP; total dystonia duration was 13.5 days. Parkinsonism peaked a median of 19.5 days after MPTP, remaining nearly constant thereafter. Peak dystonia severity highly correlated with parkinsonism severity (r[18] = 0.82, p < 0.001). Residual cell counts in lesioned nigra correlated linearly with peak dystonia scores (r[18] = -0.68, p=<0.001). Dystonia was not observed in monkeys without striatal dopamine depletion (n = 2); dystonia severity correlated with striatal dopamine depletion when residual nigral cell loss was less than 50% ([11] r = -0.83, p < 0.001) but spanned a broad range with near complete striatal dopamine depletion, when nigral cell loss was greater than 50%. Our data indicate that residual striatal dopamine may not reflect dystonia severity. We speculate on mechanisms of transient dystonia followed by parkinsonism that may be studied using this particular NHP MPTP model to better understand relationships of transient dystonia to nigrostriatal injury and parkinsonism.

[Clinical value of lymph node dissection of No. 14cd during pancreaticoduodenectomy in patients with pancreatic head carcinoma].

Objectives: To evaluate the positive rate of left posterior lymph nodes of the superior mesenteric artery (14cd-LN) in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma,to analyze the impact of 14cd-LN dissection on lymph node staging and tumor TNM staging. Methods: The clinical and pathological data of 103 consecutive patients with pancreatic cancer who underwent pancreaticoduodenectomy at Pancreatic Center,the First Affiliated Hospital of Nanjing Medical University from January to December 2022 were analyzed,retrospectively. There were 69 males and 34 females,with an age(M (IQR))of 63.0 (14.0) years (range:48.0 to 86.0 years). The χ2 test and Fisher's exact probability method was used for comparison of the count data between the groups,respectively. The rank sum test was used for comparison of the measurement data between groups. Univariate and multivariate Logistic regression analyzes were used for the analysis of risk factors. Results: All 103 patients underwent pancreaticoduodenectomy successfully using the left-sided uncinate process and the artery first approach. Pathological examination showed pancreatic ductal adenocarcinoma in all cases. The location of the tumors was the pancreatic head in 40 cases,pancreatic head-uncinate in 45 cases,and pancreatic head-neck in 18 cases. Of the 103 patients,38 cases had moderately differentiated tumor and 65 cases had poorly differentiated tumor. The diameter of the lesions was 3.2 (0.8) cm (range:1.7 to 6.5 cm),the number of lymph nodes harvested was 25 (10) (range:11 to 53),and the number of positive lymph nodes was 1 (3) (range:0 to 40). The lymph node stage was stage N0 in 35 cases (34.0%),stage N1 in 43 cases (41.7%),and stage N2 in 25 cases (24.3%). TNM staging was stage ⅠA in 5 cases (4.9%),stage ⅠB in 19 cases (18.4%),stage ⅡA in 2 cases (1.9%),stage ⅡB in 38 cases (36.9%),stage Ⅲ in 38 cases (36.9%),and stage Ⅳ in 1 case (1.0%). In 103 patients with pancreatic head cancer,the overall positivity rate for 14cd-LN was 31.1% (32/103),and the positive rates for 14c-LN and 14d-LN were 21.4% (22/103) and 18.4% (19/103),respectively. 14cd-LN dissection increased the number of lymph nodes (P<0.01) and positive lymph nodes (P<0.01). As a result of the 14cd-LN dissection,the lymph node stage was changed in 6 patients,including 5 patients changed from N0 to N1 and 1 patient changed from N1 to N2. Similarly,the TNM stage was changed in 5 patients,including 2 patients changed from stage ⅠB to ⅡB,2 patients changed from stage ⅡA to ⅡB,and 1 patient changed from stage ⅡB to Ⅲ. Tumors located in the pancreatic head-uncinate (OR=3.43,95%CI:1.08 to 10.93,P=0.037) and the positivity of 7,8,9,12 LN (OR=5.45,95%CI:1.45 to 20.44,P=0.012) were independent risk factors for 14c-LN metastasis; while tumors with diameter >3 cm (OR=3.93,95%CI:1.08 to 14.33,P=0.038) and the positivity of 7,8,9,12 LN (OR=11.09,95%CI:2.69 to 45.80,P=0.001) were independent risk factors for 14d-LN metastasis. Conclusion: Due to its high positive rate in pancreatic head cancer,dissection of 14cd-LN during pancreaticoduodenectomy should be recommended,which can increase the number of lymph nodes harvested,provide a more accurate lymph node staging and TNM staging.

Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo.

Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of cancers, including esophageal squamous cell carcinoma (ESCC). However, the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge. By RNA-sequencing analysis, we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA. LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion. Silencing of LLNLR-299G3.1 with ASO (antisense oligonucleotide) resulted in opposite effects. Mechanistically, LLNLR-299G3.1 bound to cancer-associated RNA binding proteins and regulated the expression of cancer-related genes, including OSM, TNFRSF4, HRH3, and SSTR3. ChIRP-seq (chromatin isolation by RNA purification and sequencing) revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1. Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4. Therapeutically, intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide (pICSA-BP-ANPs) strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo. Overall, our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.