Objective To explore the model of decreased ovarian reserve(DOR)induced by experimental autoimmune thyroiditis(EAT)in mice and investigate the protective mechanism of Jiexu Zichong Granules(ZCWS).Methods Ninety-six Kunming female mice were randomly divided into the J control group,BIW control group,J model group,and BIW model group.The mice were immunized with antigen(0.1 mg,once or twice per week)combined with high iodine water(0.64 g/L)for 7-19 weeks to validate the model.Subsequently,30 mice were randomly divided into the ZCWS group,model group,and control group.The DOR model was established by immunization with the antigen(0.2 mg per week)combined with high iodine water feeding for 13 weeks.The ZCWS group received oral administration of traditional Chinese medicine suspension(0.64 g/mL),while the remaining groups received an equivalent volume of physiological saline for 7 weeks.Thyroid and ovarian tissue morphology and related indicators were detected using HE staining,ELISA,IHC,and Western blot.Results Antigen immunization for 13 weeks(0.1-0.2 mg per week)combined with high iodine water feeding stably constructed the EAT DOR model.ZCWS reduced thyroid lymphocyte infiltration,follicular structure destruction,and serum TPOAb and TGAb levels(P<0.01).It inhibited MDA activity(P<0.01),increased GSH-Px and SOD activities(P<0.05),increased primordial,primary,and secondary follicles(P<0.05),and reduced atretic follicles(P<0.01).ZCWS upregulated AMH and downregulated FSH(P<0.01),regulated the expression of Bcl-2,Bax,and Caspase-3 proteins in ovarian tissue,downregulated Keap1 protein(P<0.01),and upregulated Nrf2(P<0.01),HO-1,and LONP1 proteins(P<0.05).It upregulated Bcl-2 protein(P<0.05),downregulated Bax(P<0.01),and Caspase-3(P<0.05)proteins,downregulated Keap1 protein(P<0.01),and upregulated Nrf2(P<0.01),HO-1,and LONP1 proteins(P<0.05)in ovarian tissue.Conclusion ZCWS improves ovarian reserve function in EAT mice by activating the Nrf2 pathway,inhibiting oxidative stress,and reducing follicular atresia.

A 45-year-old male patient with type 2 diabetes developed euglycemic diabetic ketoacidosis(euDKA)after combined use of ertugliflozin and metformin.Four days after medication,the patient developed chest tightness,shortness of breath,fever,accompanied by urinary frequency and dysuria.Laboratory findings showed random blood glucose of 6.5 mmol·L-1,ketone bodies of 3.1 mmol·L-1,and metabolic acidosis on arterial blood gas analysis(pH 7.27,actual bicarbonate 6.9 mmol·L-1).EuDKA was diagnosed,with suspected urinary tract infection.Ertugliflozin was promptly discontinued.Treatments such as fluid resuscitation,low-dose insulin infusion via pump,electrolyte correction,and anti-infective therapy were administred.Symptoms gradually improved,and ketone bodies turned negative after three days.Using the Naranjo's Assessment Scale,the association between euDKA and the suspected drug ertugliflozin was rated as"probable"(score 7).This case suggested that concomitant use of SGLT2 inhibitors and metformin,especially with co-existing infection,may significantly increase the risk of euDKA.Enhanced medication evaluation and monitoring were recommended in clinical practice.

Objective:To establish and validate a predictive model for non-curative resection of rectal neuroendocrine tumors (R-NETs) ≤20 mm.Methods:Data from patients with R-NETs treated at the First Affiliated Hospital of Soochow University and the Suzhou Ninth People's Hospital from January 2013 to December 2023 were retrospectively analyzed. Clinical data, endoscopic findings, and pathological characteristics were analyzed. Univariate analysis was performed using independent sample t-tests and Chi-square tests. Variables were screened using the forward stepwise binary logistic regression to establish a risk prediction model for non-curative resection of R-NETs ≤20 mm, with subsequent construction of a nomogram. The performance of the model was evaluated using the receiver operating characteristic (ROC) curve. The consistency between predicted and observed probabilities was assessed using calibration curves, and the clinical net benefit of the model was evaluated using decision curve analysis. Results:A total of 213 patients were included, with age of 50.53±11.42 years, and 102 (47.9%) were male. The distance of the lesion from the dentate line was 7.11±2.79 cm, and the tumor long diameter was 8.24±3.75 mm. Compared to curative resection cases, non-curative resection cases were more likely to exhibit tumor surface depression, higher tumor G-stage, higher Ki-67 index and higher chromograninA (CgA) positivity rate ( P<0.05). Through forward variable selection in binary logistic regression, a model was established with Ki-67 index ( P=0.014, OR=1.214, 95% CI: 1.039-1.417), surface depression ( P=0.027, OR=2.348, 95% CI: 1.100-5.013), and CgA positivity ( P<0.001, OR=5.399, 95% CI: 2.764-10.544) as parameters, with a corresponding nomogram. The area under the ROC curve of the model was 0.766 (95% CI: 0.696-0.837), and clinical decision curve analysis confirmed its good clinical net benefit. The calibration curve showed good consistency between predicted and observed probabilities. Conclusion:This study establishes a risk prediction model for non-curative resection of R-NETs ≤20 mm based on surface depression, Ki-67 index, and CgA positivity. The model demonstrates strong predictive performance and offers valuable guidance for clinical endoscopists.

Objective:To assess the impact of different exercise modalities on cognitive and physical functions in elderly patients with cognitive frailty using a network meta-analysis based on frequency theory.Methods:A comprehensive computer and manual search was conducted in PubMed, Web of Science, Embase, CINAHL, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for randomized controlled trials on the effects of exercise training on cognitive and physical functions in elderly patients with cognitive frailty. The search covered studies published until December 31, 2023. To ensure the rigor of the study, two researchers independently screened the literature, evaluated the quality using the Cochrane risk of bias tool, and extracted data. Statistical analysis was conducted using Stata 14.0 software.Results:A total of 16 studies were included, involving 10 different exercise interventions (Baduanjin, Tai Chi Chuan, Mindfulness-based Tai Chi Chuan, Otago exercise, high-intensity interval training, dual-task exercise training, multicomponent exercise, aerobic exercise, resistance exercise, and combined aerobic and resistance exercise). The network meta-analysis results showed that, compared with non-exercise control groups, Baduanjin and dual-task exercise training improved cognitive function in elderly patients with cognitive frailty ( P<0.05), with Baduanjin showing the best effect ( SUCRA=0.79). Multicomponent exercise improved frailty ( P<0.05) with the best effect ( SUCRA=1.00), it also improved grip strength ( P<0.05), with the best effect ( SUCRA=0.89). Multicomponent exercise and dual-task exercise training improved walking speed ( P<0.05), multicomponent exercise had the best effect ( SUCRA=1.00) . Conclusions:Baduanjin has an advantage in improving cognitive function in elderly patients with cognitive frailty, while multicomponent exercise is more effective in improving frailty, grip strength, and walking speed. However, the conclusions of this study need further validation.

A 45-year-old male patient with type 2 diabetes developed euglycemic diabetic ketoacidosis(euDKA)after combined use of ertugliflozin and metformin.Four days after medication,the patient developed chest tightness,shortness of breath,fever,accompanied by urinary frequency and dysuria.Laboratory findings showed random blood glucose of 6.5 mmol·L-1,ketone bodies of 3.1 mmol·L-1,and metabolic acidosis on arterial blood gas analysis(pH 7.27,actual bicarbonate 6.9 mmol·L-1).EuDKA was diagnosed,with suspected urinary tract infection.Ertugliflozin was promptly discontinued.Treatments such as fluid resuscitation,low-dose insulin infusion via pump,electrolyte correction,and anti-infective therapy were administred.Symptoms gradually improved,and ketone bodies turned negative after three days.Using the Naranjo's Assessment Scale,the association between euDKA and the suspected drug ertugliflozin was rated as"probable"(score 7).This case suggested that concomitant use of SGLT2 inhibitors and metformin,especially with co-existing infection,may significantly increase the risk of euDKA.Enhanced medication evaluation and monitoring were recommended in clinical practice.

Objective:To explore the predictive value of preoperative frailty assessment using the Geriatric 8 (G8) screening tool for postoperative complications in elderly patients with radical prostatectomy.Methods:In this prospective cohort study, 145 elderly patients who underwent radical prostatectomy in the Urology Department of the Affiliated Central Hospital of Jiangnan University between September 2023 and March 2024 were selected using convenience sampling method. Preoperatively, frailty was assessed using the G8 screening tool. Postoperatively, complications within 30 days were evaluated using the Clavien-Dindo classification. The predictive value of the G8 frailty score for postoperative complications was analyzed using the receiver operating characteristic (ROC) curve.Results:The preoperative frailty incidence among the 145 elderly patients with radical prostatectomy was 43.45% (63/145). The postoperative complication rate was 63.49% (40/63) in the frail patients and 13.41% (11/82) in the non-frail patients, with a statistically significant difference (χ 2=39.184, P<0.01). After adjusting for age, smoking history, polypharmacy, albumin, tumor stage, International Prostate Symptom Score, and activities of daily living, the risk of postoperative complications in the frail patients was 6.011 times higher than in the non-frail patients [ OR=6.011, 95% CI (2.177, 16.594) ]. The area under the ROC curve for G8 frailty score in predicting postoperative complications was 0.798 [95% CI (0.723, 0.873) ] . Conclusions:Elderly patients undergoing radical prostatectomy with frailty have a higher incidence of postoperative complications. G8 screening tool has good efficacy in predicting the risk of postoperative complications in elderly prostate cancer patients.

Objective:To establish and validate a predictive model for non-curative resection of rectal neuroendocrine tumors (R-NETs) ≤20 mm.Methods:Data from patients with R-NETs treated at the First Affiliated Hospital of Soochow University and the Suzhou Ninth People's Hospital from January 2013 to December 2023 were retrospectively analyzed. Clinical data, endoscopic findings, and pathological characteristics were analyzed. Univariate analysis was performed using independent sample t-tests and Chi-square tests. Variables were screened using the forward stepwise binary logistic regression to establish a risk prediction model for non-curative resection of R-NETs ≤20 mm, with subsequent construction of a nomogram. The performance of the model was evaluated using the receiver operating characteristic (ROC) curve. The consistency between predicted and observed probabilities was assessed using calibration curves, and the clinical net benefit of the model was evaluated using decision curve analysis. Results:A total of 213 patients were included, with age of 50.53±11.42 years, and 102 (47.9%) were male. The distance of the lesion from the dentate line was 7.11±2.79 cm, and the tumor long diameter was 8.24±3.75 mm. Compared to curative resection cases, non-curative resection cases were more likely to exhibit tumor surface depression, higher tumor G-stage, higher Ki-67 index and higher chromograninA (CgA) positivity rate ( P<0.05). Through forward variable selection in binary logistic regression, a model was established with Ki-67 index ( P=0.014, OR=1.214, 95% CI: 1.039-1.417), surface depression ( P=0.027, OR=2.348, 95% CI: 1.100-5.013), and CgA positivity ( P<0.001, OR=5.399, 95% CI: 2.764-10.544) as parameters, with a corresponding nomogram. The area under the ROC curve of the model was 0.766 (95% CI: 0.696-0.837), and clinical decision curve analysis confirmed its good clinical net benefit. The calibration curve showed good consistency between predicted and observed probabilities. Conclusion:This study establishes a risk prediction model for non-curative resection of R-NETs ≤20 mm based on surface depression, Ki-67 index, and CgA positivity. The model demonstrates strong predictive performance and offers valuable guidance for clinical endoscopists.

Objective To investigate the mechanism by which angiotensin Ⅱ type 1 receptor autoantibody(AT1-AA)promotes phenotypic switch of vascular smooth muscle cells(VSMCs)and vascular fibrosis through abnormal expression of circadian clock protein BMAL1.Methods Twelve male SD rats(6～8 weeks old,weighing 180～220 g)were randomly divided into(n=6)a control group and an AT1-AA-positive group[established by active immunization of SD rats with AT1R extracellular loop Ⅱ peptide(AT1R-ECLⅡ)].HE and Masson stainings were used to observe structural changes and fibrosis in the thoracic aorta(n=3).Western blotting was performed to detect the expression of Collagen I,phenotypic switch-related proteins(SM22,α-SMA,OPN and MMP2)in vascular tissues and primary VSMCs(n=4),as well as the expression of BMAL1 at CT0,CT4,CT8,CT12,CT16,and CT20.Transwell and scratch assays were used to assess the proliferation and migration of VSMCs(n=3).si-RNA was employed to knock down Bmal1,followed by detection of BMAL1,Collagen I,and phenotypic conversion-related protein expression(n=3).Additionally,AT1-AA-positive AT1R-knockout(AT1R-KO)rats were constructed to measure BMAL1 expression in thoracic aortic tissues(n=4).Results The AT1-AA-positive rats had significantly thickened thoracic aortic vessel wall[(140±9)%vs(120±5)%,P<0.05],badly arranged VSMCs,obvious blue Masson staining,and up-regulated Collagen I expression(P<0.05).In the thoracic aorta of AT1-AA-positive rats and AT1-AA-treated VSMCs,the expression of contractile phenotype-related proteins(α-SMA,SM22)was decreased(P<0.05),while the expression of synthetic phenotype-related proteins(OPN,MMP2)was increased(P<0.05).AT1-AA enhanced the scratch healing ability and migration ability of VSMCs.Furthermore,both mRNA and protein levels of Bmal1 were significantly up-regulated at CT12(P<0.05),and the rhythmicity of Bmal1 was lost.Knockdown of Bmal1 partially ameliorated AT1-AA-induced phenotypic switch of VSMCs.Compared with AT1-AA-positive WT rats,AT1-AA-positive AT1R-KO rats showed significantly reduced BMAL1 expression in the thoracic aorta(1.35±0.06 vs 0.86±0.07,P<0.001).At the cellular level,AT1-AA-induced phenotypic switch and high Collagen I expression in VSMCs were partially improved in AT1R-KO VSMCs.Conclusion AT1-AA promotes VSMCs phenotypic conversion and vascular fibrosis through the AT1R-Bmal1 axis.

Objective:To investigate the epileptogenic networks of bilateral asymmetric tonic seizures (BATS) originating from the posterior insula using stereo-electroencephalography (SEEG).Methods:A retrospective analysis was performed. Among the epilepsy patients who underwent preoperative assessment and SEEG monitoring in the Epilepsy Department of Guangdong Sanjiu Brain Hospital from January 1, 2015 to July 1, 2024, 7 patients with insular epilepsy characterized by BATS originating from the posterior insula were selected based on anatomo-electro-clinical characteristics. The clinical characteristics, neuroimaging features, scalp EEG patterns, and SEEG recordings of the 7 patients were collected and analyzed. Via synchronously analyzing ictal semiology and electroanatomical propagation pathways shown by SEEG, the features of epileptogenic networks were elucidated. Results:Four patients had seizure onset from the dorsal-superior part of the left posterior insula, and 3 patients from the dorsal-superior part of the right posterior insula. The electroencephalographic characteristics of the seizure onset zones showed high consistency in these 7 patients: rhythmic spike or multiple spike discharges at the initial stage, and a low-amplitude rapid rhythm pattern subsequently. Totally, 3-10 seizures were recorded in each patient. Four patients experienced prodromal symptoms, including 3 patients with somatosensory symptoms (1 with chest and abdominal pain, 1 with contralateral facial numbness combined with throat constriction sensation, and 1 with contralateral limb numbness), and 1 patient with non-specific presentation (hugging family member before seizure). The seizure semiological evolution sequence was from prodrome to BATS, and then to secondary symptoms, with 3 patients exhibiting clustered spasms as secondary symptoms, and 4 patients showing eyelids and contralateral upper limb distal tonic-clonic manifestations as secondary symptoms. The epileptogenic networks followed a consistent pattern: the dorsal-superior part of the posterior insula leads to the middle-posterior part of the superior circular sulcus, to the ventral posterior insular and posterior circular sulcus, and then to the supplementary sensorimotor area (SSMA), and finally to the central sulcus, central region-vertex, and inferior parietal lobule. Only 2 patients had the anterior insular-involved epileptic brain networks, while the remaining 5 patients did not involve the anterior insular. During BATS, SEEG electrode contacts corresponding to the posterior insular, superior circular sulcus and SSMA exhibited low-amplitude rapid rhythm patterns.Conclusion:The seizures spread from the dorsal-superior part of the posterior insula to the middle-posterior part of the superior circular sulcus at the early stage of onset, and then connected with SSMA; these structures formed a epileptogenic brain network through abnormal synchronous discharge, which eventually led to BATS.

Objective To analyze the characteristics of the crown-root ratios of the anterior teeth in subjects with different periodontal phenotypes in healthy population.Methods A total of 100 periodontally healthy young volunteers were selected,there were 53 females and 47 males,totaling 594 anterior teeth were included in the study.The periodontal probe method was used to determine the periodontal phenotypes of different tooth positions,with 108 cases of thick gingival type and 90 cases of thin gingival type in mesial incisors;95 teeth of thick gingival type and 103 teeth of thin gingival type in lateral incisors,and 98 teeth of thick gingival type and 100 teeth of thin gingival type in cuspids.Panoramic radiographs were taken,crown length and root length of upper anterior teeth were calculated,and crown-root ratio was calculated,to compare and analyze the differences between the results of the two groups.Results The crown-to-root ratio in thin gingival group of mesial incisors and lateral incisors were higher than those in thick gingival group,and the root length was smaller than thick gingival group.The difference was statistically significant(P＜0.05).The keratinized gingival width of thin gingival group was less than that of thick gingival group,and the difference was statistically significant(P＜0.05).Conclusion The relatively high crown-to-root ratio of mesial incisors and lateral incisors in patients with thin gingival phenotypes and the lesser width of keratinized gingiva in thin gingival phenotypes than thick gingival phenotypes.and risk assessment should be taken into account in the restorative system as well as in the orthodontic design of the anterior tooth movement.