[Comparison of analgesic effect of modified superior trunk block and traditional interscalene brachial plexus block with liposomal bupivacaine after arthroscopic rotator cuff repair].

Objective: To compare the postoperative analgesic effect of modified superior trunk block and traditional interscalene brachial plexus block in arthroscopic rotator cuff repair. Methods: A total of 40 patients undergoing arthroscopic rotator cuff repair in the Second Affiliated Hospital of Wenzhou Medical University from October to November 2023 were prospectively included, whose American Society of Anesthesiologists (ASA) grade were Ⅰ-Ⅱ. They were divided into modified superior trunk block group (group S) and interscalene brachial plexus block group (group I) by random number table according to different nerve block methods, with 20 cases in each group. Local anesthetics was a mixture of 1.33% liposomal bupivacaine and 0.5% levobupivacaine hydrochloride injection in equal volume. Patients in group S were injected 5 ml mixture for ultrasound-guided modified superior trunk block, and patients in group I were injected with 15 ml mixture for ultrasound-guided traditional interscalene block respectively. Both groups underwent superficial cervical plexus block (5 ml mixture). Standardized general anesthesia and standardized postoperative analgesia were followed. The primary outcome measures included 48 h resting numerical rating scale (NRS) scores after surgery and the incidence of hemidiaphragmatic paralysis (HDP) at 30 min after block. The secondary outcome measures included resting NRS scores during the post anesthesia care unit (PACU), 12, 24, and 36 h after surgery, postoperative opioid consumption and satisfaction with analgesia, pulse oxygen saturation (SpO2) at 30 min after block, sensory and motor block duration, and the incidence of perioperative adverse reactions. The non-inferiority cut-off value of resting NRS scores for patients in group S was set as"1 point"at each observation time point after surgery. Results: In group S, one patient was excluded because the target nerve was blocked by the subclavian vein and could not be blocked, nineteen patients [11 males and 8 females, aged (52.2±9.0) years] were eventually included. In group I, there were 7 males and 13 females, aged (55.0±5.1) years. Resting NRS scores of group S and Group I at 48 h after surgery were 0 (0, 0) and 0 (0, 0.8) point, respectively, with no statistical significance (P>0.05). The median difference was 0 (95%CI:0-0) point and the upper 95%CI was 0 point, which was lower than the preset non-inferiority cut-off value"1 point"(non-inferiority P<0.001). The incidence of HDP in group S and group I were 5% (1/19) and 75% (15/20), respectively, with statistically significant (P<0.001). There were no significant differences in resting NRS scores at PACU and 12, 24, 36 h after surgery, opioid dosage, satisfaction with analgesia, SpO2 at 30 min after block, sensory and motor block duration between two groups (all P>0.05). No respiratory adverse events such as hypoxemia and airway spasm occurred in two groups after extubation. One patient in group I showed symptoms of breath shortness when entering PACU, and 3 patients felt uncomfortable due to prolonged numbness and weakness of the blockade limb (>2 days). No nerve block procedures and opioid drugs relative adverse reactions and no neurological complications happened in both groups. Conclusion: Liposomal bupivacaine usage for modified superior trunk block can provide long-term postoperative analgesic effects which is noninferior to traditional interscalene brachial plexus block and causes less HDP in patients undergoing arthroscopic rotator cuff repair.

Pharmacodynamic profiling in three patients with molybdenum cofactor deficiency type A reveals prolonged biological effects after withdrawal of cyclic pyranopterin monophosphate.

Molybdenum cofactor deficiency type A has successfully been treated in a small number of children with daily intravenous administration of cyclic pyranopterin monophosphate. Pharmacodynamic data for this novel treatment have not been published and alternative dosing intervals have not been explored. We monitored pharmacodynamic biomarkers of sulfite oxidase and xanthine oxidoreductase activity in three patients with MoCD-A for a period of 2 to 9 months after discontinuation of cPMP substitution. We found that the clinical and metabolic effects were sustained for longer than expected, over 7 days at least. Our data implicate a biological half-life of the molybdenum cofactor dependent enzyme activities of approximately 3 days and suggest the possibility that less frequent than once daily dosing intervals could be a safe alternative to current practice.

[Pathogenesis and treatment decisions of degenerative lumbar scoliosis].

Degenerative lumbar scoliosis (DLS) is a spinal deformity characterized primarily by abnormal curvature of the lumbar vertebrae, commonly occurring in individuals aged 50 and above. Its pathogenesis involves various factors, including intervertebral disc degeneration, ligament and muscle degradation, as well as genetic and environmental elements. In terms of treatment, non-surgical treatments such as pharmacotherapy, physical therapy, and exercise are regarded as the primary approach. However, for severe cases, individualized surgical intervention is also a viable option, and reasonable classification is the key to surgical decision-making. Current research predominantly emphasizes the osseous structural aspects of the spine, neglecting neural and muscular factors. Future interdisciplinary research is expected to explore more comprehensive and effective treatment modalities, aiding in the restoration of spinal cord function in patients.

[Construction and verification of pancreatic fistula risk prediction model after pancreaticoduodenectomy based on ensemble machine learning].

Objective: To construct an ensemble machine learning model for predicting the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy and evaluate its application value. Methods: This is a research on predictive model. Clinical data of 421 patients undergoing pancreaticoduodenectomy in the Department of Pancreatic Surgery,Union Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology from June 2020 to May 2023 were retrospectively collected. There were 241 males (57.2%) and 180 females (42.8%) with an age of (59.7±11.0)years (range: 12 to 85 years).The research objects were divided into training set(315 cases) and test set(106 cases) by stratified random sampling in the ratio of 3∶1. Recursive feature elimination is used to screen features,nine machine learning algorithms are used to model,three groups of models with better fitting ability are selected,and the ensemble model was constructed by Stacking algorithm for model fusion. The model performance was evaluated by various indexes,and the interpretability of the optimal model was analyzed by Shapley Additive Explanations(SHAP) method. The patients in the test set were divided into different risk groups according to the prediction probability (P) of the alternative pancreatic fistula risk score system (a-FRS). The a-FRS score was validated and the predictive efficacy of the model was compared. Results: Among 421 patients,CR-POPF occurred in 84 cases (20.0%). In the test set,the Stacking ensemble model performs best,with the area under the curve (AUC) of the subject's work characteristic curve being 0.823,the accuracy being 0.83,the F1 score being 0.63,and the Brier score being 0.097. SHAP summary map showed that the top 9 factors affecting CR-POPF after pancreaticoduodenectomy were pancreatic duct diameter,CT value ratio,postoperative serum amylase,IL-6,body mass index,operative time,albumin difference before and after surgery,procalcitonin and IL-10. The effects of each feature on the occurrence of CR-POPF after pancreaticoduodenectomy showed a complex nonlinear relationship. The risk of CR-POPF increased when pancreatic duct diameter<3.5 mm,CT value ratio<0.95,postoperative serum amylase concentration>150 U/L,IL-6 level>280 ng/L,operative time>350 minutes,and albumin decreased by more than 10 g/L. The AUC of a-FRS in the test set was 0.668,and the prediction performance of a-FRS was lower than that of the Stacking ensemble machine learning model. Conclusion: The ensemble machine learning model constructed in this study can predict the occurrence of CR-POPF after pancreaticoduodenectomy,and has the potential to be a tool for personalized diagnosis and treatment after pancreaticoduodenectomy.

[Clinicopathological features and prognosis of sporadic mismatch repair deficient colorectal cancer].

Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side (P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Surface Fluorination of Nuclear Graphite Exposed to Molten 2LiF-BeF2 (FLiBe) Salt and Its Cover Gas at 700 °C.

This study demonstrates that the reaction of Li2BeF4 (FLiBe) with graphite both in the liquid phase and the gas phase of the molten salt leads to the formation of covalent and semi-ionic carbon-fluorine bonds at the graphite surface and is accompanied by surface microstructural changes, removal of C-O groups, and deposition of metallic beryllium, based on XPS, Raman, and glow discharge mass spectroscopy characterization. At 700 °C, the observed surface density of C-F is higher after 240 h than after 12 h of exposure to molten FLiBe salt; the kinetics of covalent C-F formation is slower than that of semi-ionic C-F formation, and the relative amount of semi-ionic C-F content increases with depth. The graphite sample exposed to the cover gas exhibits less surface fluorination than the salt-exposed sample, with predominantly semi-ionic C-F. Based on these observations and the observed LiF/BeF2 ratio by surface XPS, the hypotheses that fluorination of the salt-exposed graphite occurs via a gas-phase mechanism or that it requires salt intrusion are refuted; future studies are warranted on the transport of C-F semi-ionic and covalent species in graphite at high temperatures.

Predicting Cognitive Decline for Non-Demented Adults with High Burden of Tau Pathology, Independent of Amyloid Status.

BACKGROUND: Abnormal tau proteins are independent contributors to cognitive impairment. Nevertheless, not all individuals exposed to high-level tau pathology will develop cognitive dysfunction. We aimed to construct a model to predict cognitive trajectory for this high-risk population. METHOD: Longitudinal data of 181 non-demented adults (mean age= 73.1; female= 45%), who were determined to have high cerebral burden of abnormal tau by cerebrospinal fluid (CSF) measurements of phosphorylated tau (ptau181) or total tau, were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Cognitive decline was defined as Mini-Mental State Examination scores decline ≥ 3 over three years. A predictive nomogram was constructed using stepwise backward regression method. The discrimination, calibration, and clinical usefulness of the nomogram were evaluated. The model was validated in another 189 non-demented adults via a cross-sectional set (n=149, mean age = 73.9, female = 51%) and a longitudinal set (n= 40, mean age = 75, female = 48%). Finally, the relationships of the calculated risk scores with cognitive decline and risk of Alzheimer's disease were examined during an extended 8-year follow-up. RESULT: Lower volume of hippocampus (odds ratio [OR] = 0.37, p< 0.001), lower levels of CSF sTREM2 (OR = 0.76, p = 0.003), higher scores of Alzheimer's Disease Assessment Scale-Cognitive (OR = 1.15, p = 0.001) and Functional Activities Questionnaire (OR = 1.16, p = 0.016), and number of APOE ε4 (OR = 1.88, p = 0.039) were associated with higher risk of cognitive decline independent of the amyloid status and were included in the final model. The nomogram had an area of under curve (AUC) value of 0.91 for training set, 0.93 for cross-sectional validation set, and 0.91 for longitudinal validation set. Over the 8-year follow-up, the high-risk group exhibited faster cognitive decline (p< 0.001) and a higher risk of developing Alzheimer's dementia (HR= 6.21, 95% CI= 3.61-10.66, p< 0.001 ). CONCLUSION: APOE ε4 status, brain reserve capability, neuroinflammatory marker, and neuropsychological scores can help predict cognitive decline in non-demented adults with high burden of tau pathology, independent of the presence of amyloid pathology.

[Pituitary Crooke cell neuroendocrine tumor of adrenocorticotropic hormone differentiation-specific transcription factor lineage: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors. Methods: Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed. Results: Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing's syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas. Conclusions: Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.

The inhibition roles of RAB23 gene in granulosa cell proliferation and progesterone synthesis of hen ovarian prehierarchical follicles.

1. The proliferation of granulosa cells is vital for the development and recruitment of hen ovarian prehierarchical follicles (PF). The RAB23 protein is a member of the Rab family, belonging to the GTPase family. This study studied the regulatory roles of the RAB23 gene in PF.2. The expression of RAB23 was significantly increased in granulosa cells (GC) during PF growth and was highest in GC at 6-8 mm diameter (p < 0.05). The RAB23 protein was mainly expressed in the GC, oocytes (OC) as well as somatic cells (SC) of the PF.3. The mRNA expression of FSHR, CCND1,CYP11A1, StAR and HSD3B1 was significantly increased in the siRNA RAB23 group (p < 0.05). Additionally, protein expression of FSHR, CCND1, CYP11A1, HSD3B1 was significantly increased (p < 0.05) after GC were transfected with RAB23-specific siRNA. Protein expression of StAR in the siRNA RAB23 group was numerically higher than that in the positive control (PC) and negative control (NC) groups. The GC proliferation rate and progesterone synthesis of the prehierarchical follicles in hen ovaries were markedly increased in vitro (p < 0.05).4.This study revealed that RAB23 might play an inhibitory role in GC proliferation and progesterone synthesis during the prehierarchical follicles development in vitro.

[Epidemiological characteristics and drug resistance of diarrheagenic Escherichia coli infection in diarrhea patients in Shanghai, 2016-2022].

Objective: To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods: The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results: In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions: Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.

[Association between intraoperative hypothermia and outcomes in neonatal patients undergoing non-cardiac surgery].

Objective: To investigate the impact of intraoperative hypothermia on postoperative outcome in neonatal patients undergoing non-cardiac surgery. Methods: The data of 1 008 neonates undergoing non-cardiac surgery in Children's Hospital, Zhejiang University School of Medicine from January 2020 to October 2022 were retrospectively collected,which included 558 males and 450 females, with a midian age [M (Q1, Q3)] of 6 (2, 14) days. Neonates were divided into 4 groups according to whether hypothermia (below 36 ℃) occurred and the lowest body temperature during the surgery: normal temperature group (n=246), mild hypothermia group (the lowest temperature ranged 35.0-35.9 ℃, n=434), moderate hypothermia group (the lowest temperature ranged 34.0-34.9 ℃, n=232) and severe hypothermia group (the lowest temperature<34 ℃, n=96). The primary outcome was the incidence of intraoperative hypothermia. The four groups' difference of postoperative hospital stay, postoperative mortality within 30 days, postoperative pulmonary complications, postoperative hemorrhage/blood transfusion and acidosis were compared. Multivariate logistic regression was used to analyze the relationship between intraoperative hypothermia and prolonged postoperative hospital stay (>14 d), 30 d-mortality and other complications. Results: In the 1 008 neonatal patients, 762 (75.6%) cases suffered intraoperative hypothermia, among which the incidence of mild, moderate and severe hypothermia was 43.1% (434/1008), 23.0% (232/1008) and 9.5% (96/1008), respectively. The postoperative hospital stay in normal, mild, moderate and severe hypothermia groups was 9.0 (5.8, 18.0), 12.0 (7.0, 21.0), 17.0 (10.0, 34.5) and 31.5 (12.5, 55.8) days. The mortality rate with 30 days after surgery was 2.9% (7/246), 4.4% (19/434), 6.9% (16/232) and 14.7% (14/96), the incidence of postoperative pulmonary complications was 31.7%(78/246), 39.9%(173/434), 44.8%(104/232) and 67.4%(64/96), the rate of postoperative hemorrhage/blood transfusion was 19.9%(49/246), 32.3%(140/434), 49.1%(114/232) and 79.0%(75/96), and the incidence of acidosis was 26.8%(66/246), 35.7%(155/434), 44.4%(103/232) and 46.3%(44/96), respectively. All differences were statistically significant (all P<0.05). According to the adjusted logistic regression analysis, compared with the normal body temperature group, severe hypothermia was associated with prolonged postoperative hospital stay (OR=1.962, 95%CI: 1.063-3.619) and postoperative pulmonary complications (OR=2.020, 95%CI: 1.149-3.553). The mild, moderate and severe hypothermia group could increase the risk of postoperative blood/transfusion rate (mild: OR=1.690, 95%CI: 1.080-2.644; Moderate: OR=2.382, 95%CI: 1.444-3.927; Severe: OR=8.334, 95%CI: 3.123-8.929). The mild and moderate hypothermia could raise the risk of acidosis (mild: OR=1.458, 95%CI: 1.009-2.107; Moderate: OR=1.949, 95%CI: 1.279-2.972). Conclusion: Intraoperative hypothermia can prolong the postoperative hospital stay, and increase the risk of postoperative mortality, postoperative pulmonary complications, postoperative hemorrhage/transfusion, and acidosis.

[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

[Retrospective clinicopathological analysis of pulmonary light chain deposition disease secondary to Sjögren's syndrome].

Objective: To analyze of the clinical, imaging, and pathological features of pulmonary light chain deposition disease(PLCDD) secondary to Sjögren's syndrome(SS), and to improve the understanding of the disease. Methods: We retrospectively analyzed the clinical data of 23 PLCDD cases diagnosed by pathology in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2009 to 2023, a total of 11 cases of PLCDD secondary to SS(SS-PLCDD) were selected, the median age was 51 years old(range:36~74),10 female and 1 male, the clinical, imaging, and pathological features were summarized. Results: All 11 cases showed bilateral multiple pulmonary nodules on HRCT with 10 cases accompanied by cysts, 6 cases with vessels in the cystic wall or crossing the cysts. Microscopically, all 11 cases showed amorphous eosinophilic material with negative Congo red staining deposited in the lung, vascular involvement was common, with variable lymphocyte, plasma cell infiltration and multinucleated giant cell reaction, cysts formation was observed in 6 cases,1 case combined with pulmonary lymphoma. No extrapulmonary involvement in all 11 cases. Ten patients were treated with glucocorticoid and (or) immunosuppressants, 1 patient changed to bortezomib-dexamethasone chemotherapy after 1 year, with a mean follow-up of 50 months, 5 cases were stable on clinical and (or) HRCT findings, 2 cases showed remission on HRCT, 2 cases progressed on HRCT. Conclusions: SS-PLCDD affects predominantly middle-aged females with lesions confined to the lung; HRCT showed bilateral multiple nodules and thin-walled cysts. Pulmonary pathology presented as non-amyloid material with negative Congo red staining and interstitial changes associated with SS. The overall prognosis was good, but caution is advised regarding the underlying lymphoma.

Protocol change improves live birth and recurrent cycle cancellation rates after a previous IVF cycle cancellation: an analysis of 13 000 autologous cycles reported to SART CORS.

STUDY QUESTION: After an IVF cycle cancellation, does changing the stimulation protocol affect the odds of live birth and recurrent cancellation in the subsequent cycle? SUMMARY ANSWER: After IVF cycle cancellation, compared to those who repeated the same stimulation protocol, those who changed their protocol had higher odds of live birth and lower odds of recurrent cycle cancellation. WHAT IS KNOWN ALREADY: There is limited data addressing the effect of changing the stimulation protocol after an IVF cycle is cancelled during initial stimulation. The odds of live birth outcomes are not known so far in studies addressing the effect of changing the protocol. STUDY DESIGN, SIZE, DURATION: Retrospective Cohort Study using the 2014-2017 Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. PARTICIPANTS/MATERIALS, SETTING, METHODS: The data included 13 135 patients with a first autologous IVF cycle that resulted in a cycle cancellation and was followed by a second autologous cycle within the study period. We excluded fertility preservation cycles, supernumerary cycle attempts after the second IVF cycle attempt, and cycles with more than one stimulation protocol documented per cycle start. Patients who received the same protocol for both cycles (n = 6434) were compared to those who changed their protocol in the second cycle (n = 6701). Multivariable logistic regression analyses were performed to estimate the adjusted odds of live birth and recurrent cancellation. MAIN RESULTS AND THE ROLE OF CHANCE: Changing the protocol in the second cycle resulted 14% lower odds of recurrent cycle cancellation (P = 0.01) and 17% higher odds of live birth after fresh transfers (P = 0.04). When stratifying the data by specific combinations of protocol change (agonist flare, agonist suppression, antagonist), there was an increase in live birth when switching from antagonist to agonist suppression (odds ratio (OR) = 1.36, P = 0.03) and from agonist suppression to antagonist (OR = 1.73, P = 0.01) compared to those who repeated their same stimulation protocol. Specifically in poor responders, outcomes were worse when using the agonist flare protocol and significantly improved with the agonist suppression protocol. LIMITATIONS, REASONS FOR CAUTION: Comparison of response to stimulation between first and second cycles cannot be made in this study because the index IVF cycle was cancelled during ovarian stimulation, and thus there is no reportable outcome data for that cycle. Additionally, SART only tracks the three stimulation protocols addressed in this study and does not have data on more contemporary protocols that are used in poor responders thus limiting the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS: Using the SART CORS database, which includes >90% of all reported IVF cycles in the USA, provides generalizability to the demographically diverse IVF populations found here. In agreement with prior studies assessing change in IVF protocols, the agonist flare protocol seems to result in worse IVF outcomes, and based on our results, we believe that there is no role for the agonist flare protocol in patients with a prior poor response to stimulation. STUDY FUNDING/COMPETING INTEREST(S): None declared. TRIAL REGISTRATION NUMBER: N/A.

First Report of Diaporthe tectonendophytica Causing Leaf Spot on Dalbergia odorifera in Guangxi, China.

Dalbergia odorifera T. Chen (Family: Fabaceae) is a national level II protected plant in China, with extremely high economic value and medical properties (Zhao et al. 2020). In June 2023, an unknown leaf spot was found in a garden land of Pingxiang city, Guangxi, China, and approximately 80% of the plants covered an area of 500 m2 displayed similar symptoms. The spots were grey to white, 4~6 mm in diameter (n=30) with black pycnida on the spots surface (Fig S1, A-D). Multiple disease spots were observed on a single leaf. The pycnida on the lesion were picked and mashed, to make a conidia suspension using sterile water. The conidial solution was then spread onto a potato dextrose agar (PDA) plate containing streptomycin, with 10 mg of streptomycin per 100 mL, and incubated for 3 days at 28°C with a 12 hour photoperiod. Three isolates (GXPX01, GXPX02 and GXPX03) were obtained by re-culturing the colonies on fresh PDA plates. The colony on PDA were white with aerial mycelia (Fig S1, E-F). Black conidiomata developed at 28°C with a 12 hour photoperiod in 20 days (Fig S1, G-H). Alpha conidia were 4.2~6.4 µm × 1.8~2.6 µm (average =5.1 × 2.3 µm, n = 30), mostly bi-guttulate, hyaline, ellipsoid, apex bluntly rounded, base obtuse to subtruncate, smooth (Fig S1, I). Beta conidia were 15.1~33.5 µm × 1~1.8 µm (average = 24.5 × 1.5 µm, n = 30), filiform, hyaline, curved or hamate, aseptate, base subtruncate (Fig S1, J). Morphological characteristics of the three isolates matched those of Diaporthe spp.(Gomes et al. 2013). The rDNA internal transcribed spacer (ITS) region, the translation elongation factor 1-α (TEF1), the calmodulin (CAL), the histone H3 (HIS) and the ß-tubulin (TUB2) genes of the three isolates were amplified using the primer pairs ITS4/ITS5, EF1-728F/EF1-986R, CAL-228F/CAL2Rd, CYLH3F/H3-1B, and T1 /CYLTUB1R, respectively (Crous et al. 2004, Sun et al. 2021). The sequences were all deposited in GenBank (accession numbers OR437511 to OR437513 for ITS, OR454965 to OR454967 for TEF1, OR454968 to OR454970 for CAL, OR454971 to OR454973 for TUB2, OR454974 to OR454976 for H3). Sequences had 98.36% to 100% homology with the corresponding sequences of known Diaporthe tectonendophytica strains MFLUCC 13-0471 in the NCBI database. Phylogenetic analysis was based on combined ITS, TEF1, TUB2 and CAL sequences data using MEGA 11 software to construct phylogenetic tree with Maximum Likelihood (Doilom et al. 2017). In the phylogenetic tree, the combined sequences attributed the three isolates to the D. tectonendophytica (Fig S2). The pathogenicity was tested on leaves of 1.5-year-old D. odorifera seedlings. Three leaves were wounded with a sterile needle and individually inoculated with a 5 mm mycelial disk of PDA culture from each isolate. Sterile PDA disks inoculated leaves as a control. The test was repeated three times. The inoculated plants were placed in a greenhouse at 25℃ and 90% humidity, with a photoperiod of 12 hours. Five days after inoculation, necrotic lesions appeared on inoculated leaves and symptoms from all three isolates were the same as those form natural infections ( Fig S1, K-N), whereas all the control remained symptomless (Fig S1, P). The pathogen was reisolated from the inoculated leaves and again identified as D. tectonendophytica, with the same methodology used for the initial identification. D. tectonendophytica was reported to cause plant diseases, such as stem gray blight of red-fleshed dragon fruit (Hylocereus polyrhizus) (Rahim et al. 2021), leaf spots disease on Elaeagnus conferta and Pometia pinnata (Sun et al. 2021). To our knowledge, this is the first report of D. ctonendophytica causing leaf spot disease on D. odorifera.

ELABELA-APJ Axis Enhances Mesenchymal Stem Cell Proliferation and Migration via the METTL3/PI3K/AKT Pathway.

Mesenchymal stem cells (MSCs) possess a strong therapeutic potential in regenerative medicine. ELABELA (ELA) is a 32 amino acid peptide that binds to the apelin peptide jejunum receptor (APJ) to regulate cell proliferation and migration. The aim of this study was to investigate the function of ELA vis-a-vis the MSC proliferation and migration, and further explore the underlying mechanism. We demonstrated that the exogenous supplement of ELA boosts the proliferation and migration ability of MSCs, alongside improved in vitro cell viability. These capabilities were rendered moot upon APJ knockdown. In addition, ELA (5-20 µM) was shown to upregulate the expression of METTL3 in a concentrationdependent pattern, a capacity which was suppressed by APJ reduction, whereas the downregulation of METTL3 expression blocked the beneficial effects induced by ELA. ELA was also observed to upregulate the phosphorylation level of AKT. This ELA-induced activation of the PI3K/AKT pathway, however, is inhibited with knockdown of METTL3. Our data indicate that ELA could act as a promoter of MSC proliferation and migration in vitro through the APJ receptor, something which might be attributed to the activation of the METTL3/PI3K/AKT signaling pathway. Therefore, ELA is a candidate for optimizing MSC-based cell therapy, while METTL3 is a potential target for its promoting action on MSCs.

[Clinical study on the efficacy and safety of glaucoma drainage implants in the treatment of different types of glaucoma].

Objective: To evaluate the efficacy and safety of glaucoma drainage implants(XEN-45 Gel Stent) for glaucoma treatment. Methods: A prospective study was conducted to continuously collect the clinical data of patients who were diagnosed with glaucoma and underwent XEN-45 Gel Stent implantation in the Ophthalmology Department of Peking University People's Hospital from January 2022 to August 2023. The visual acuity, intraocular pressure, number of glaucoma medications, and success rate of the patients were analyzed before and after surgery at 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, and 18 months. The differences in intraocular pressure and number of glaucoma medications among primary open-angle glaucoma, primary angle closure glaucoma, secondary glaucoma, and different implantation methods of XEN-45 Gel Stent among patients with primary open-angle glaucoma were compared. The intraoperative and postoperative complications were observed, and the risk factors for needling and surgical complete success were analyzed. Results: A total of 48 eyes from 48 patients were included in this study, comprising 27 males and 21 females, with a mean age of (54.4±18.0) years and the disease duration was 36.0(7.3, 81.0) months.There were 28 cases of primary open-angle glaucoma, 4 cases of primary angle closure glaucoma, and 16 cases of secondary glaucoma.The follow-up period was 8.0 (3.0, 12.0) months. At 12 months after surgery, the intraocular pressure decreased from 20.5 (17.0, 26.0) mmHg to (13.5±3.3) mmHg (P<0.05), and the number of glaucoma medications decreased from 3.0 (3.0, 4.0) to 0.0 (0.0, 0.0) (P<0.05). The complete success rate and qualified success rate were 73.9% (17/23) and 91.3% (21/23), respectively. The most common postoperative complications were shallow anterior chamber in 6 cases (12.5%), hypotony in 3 cases (6.3%), and blocked stent in 3 cases (6.3%). The most common postoperative treatment was needling in 27 cases (56.3%). There was no significant difference in intraocular pressure among different types of glaucoma. In the comparison of postoperative effects of different surgical implantation methods for primary open-angle glaucoma, there were no statistically significant differences in intraocular pressure and the number of glaucoma medications at other follow-up time points except 1 month after surgery (P<0.05). Univariate logistic regression analysis did not find any risk factors associated with needling and surgical complete success. Conclusions: XEN-45 Gel Stent implantation is an effective and safe surgical option for different types of glaucoma patients in China, which can significantly reduce intraocular pressure and the use of glaucoma medications and has a high success rate. However, some patients may need needling or other treatments after surgery.