The incidence of bile duct stones, as a prevalent disorder of digestive system, has been increasing annually. Challenges such as high recurrence rates, management of complex cases, and applicability in specific populations remain in clinical practice. Endoscopic retrograde cholangiopancreatography (ERCP), renowned for its precise localization and efficient stone removal, has long been regarded as the first-line treatment for choledocholithiasis. However, the limitations of traditional X-ray-guided ERCP have spurred ongoing innovations in its technology, which is an art of balance between " preserving tradition" and " embracing innovation". This work systematically reviewed the evolution and breakthroughs of ERCP and its derivative techniques in the diagnosis and treatment of bile duct stones, with a focus on advances in the radiation-free ERCP and cholangioscopy-guided lithotripsy. Additionally, it addresses diagnostic methods for bile duct stones complicated by strictures, ERCP strategies for concurrent bile duct and gallbladder stones, and novel approaches to preserving the duodenal papilla. Nevertheless, the adoption of these innovations remains constrained for procedural complexity, equipment costs, and expertise of operator. Future efforts should emphasize the multidisciplinary collaboration, technical standardization, and optimization of devices to greater precision and less invasiveness in ERCP, making it more applicable to diverse clinical scenarios, and ultimately achieving comprehensive progress in personalized management of bile duct stones.

Objective To investigate the predictive ability of cyst fluid characteristics for malignant intraductal papillary mucinous neoplasms (IPMNs). Methods We prospectively collected fresh cyst fluid from patients undergoing pancreatic resection at the Department of Hepatobiliary Pancreatic Spleen Surgery, Changhai Hospital, Shanghai, from September 2023 to December 2024, who were ultimately pathologically confirmed with IPMN. We assessed the characteristics of cyst fluid, including viscosity, clarity, and color, and explored its predictive performance for benign or malignant. Results A total of 40 patients with IPMN were included. The sensitivity of the string sign （+） for diagnosing high-grade dysplasia/ invasive carcinoma （HGD/IC） was 90.9%, specificity was 92.9%, and accuracy was 76.0%. The cyst fluid of intestinal-type IPMN often exhibited a gelatinous consistency, and there was no significant difference in the distribution of gelatinous consistency between the HGD/IC group and the low-grade dysplasia （LGD） group. There were no significant differences in CEA, glucose, and amylase levels in the cyst fluid between the HGD/IC group and the LGD group. Conclusions The characteristics of pancreatic cyst fluid, especially viscosity, can effectively predict the benign or malignant nature of IPMN.

Objective To explore the risk factors for the recurrence of autoimmune pancreatitis(AIP),so as to provide a new reference for its clinical treatment.Methods The clinical data of 198 AIP patients admitted to The First Affiliated Hospital of Naval Medical University from 2014 to 2021 were collected,including 164 patients with type 1 AIP and 34 patients with type 2 AIP.Based on the recurrence status of AIP,the patients were categorized into recurrence group(38 cases)and non-recurrence group(160 cases),and differences between the 2 groups were analyzed.Patients with definite duration of glucocorticoid maintenance therapy were further screened,and logistic regression model and Spearman rank correlation analysis were used to analyze the risk factors of AIP recurrence.Results During the follow-up period,19.19％(38/198)of AIP patients experienced a relapse.The 1-,3-,and 5-year cumulative recurrence rates were 6.57％,9.09％,and 12.63％,respectively,with type 1 AIP demonstrating a significantly higher recurrence rate than type 2 AIP(21.95％[36/164]vs 5.88％[2/34],P=0.030).Univariate logistic regression analysis showed that serum low density lipoprotein-cholesterol level(odds ratio[OR]=0.544,95％confidence interval[CI]0.321-0.924,P=0.024)and the duration of glucocorticoid maintenance therapy(OR=0.797,95％CI 0.704-0.902,P＜0.001)were the potential factors of AIP recurrence in 112 patients with definite data on the duration of glucocorticoid maintenance therapy.Multivariate logistic regression analysis showed that the duration of glucocorticoid maintenance therapy was independently associated with AIP recurrence(OR=0.813,95％CI 0.713-0.926,P=0.002).Spearman rank correlation analysis further demonstrated a negative correlation between the duration of glucocorticoid maintenance therapy and AIP recurrence(r=-0.545,P＜0.001).Additionally,receiver operating characteristic curve analysis indicated that the duration of glucocorticoid maintenance therapy had good predictive effect on AIP recurrence,with an area under curve value of 0.873(95％CI 0.800-0.945,P＜0.001).Conclusion Long-term regular glucocorticoid therapy is an independent protective factor against AIP recurrence,and it can significantly reduce the recurrence of AIP.

BackgroundDepression in mid-to-late pregnancy has significant negative effects on pregnant women and their offspring. Previous studies have shown that pregnant women with depression in mid-to-late pregnancy exhibit lower frontal lobe activation levels， but the activation phase and its impact on depression require further investigation. ObjectiveTo analyze the functional near-infrared spectroscopy （fNIRS） features of depressed pregnant women in mid-to-late pregnancy， and to provide references for assisting in the clinical screening of depression in them. MethodsA total of 40 pregnant women in mid to late pregnancy with Edinburgh Postnatal Depression Scale （EPDS） score above 11 who underwent prenatal examination at the department of obstetrics of the Third Hospital of Mianyang from September 2023 to July 2024 were included as the study group. During the same period， 40 pregnant women in mid-to-late pregnancy with EPDS score below 11 who were matched with the age， family history， and past history of the study group were recruited as the control group. A self-designed questionnaire was used to collect basic information of the pregnant women. The fNIRS technique was used to measure the prefrontal and temporal lobe integral values and center of gravity values during the verbal fluency task （VFT） pregnant women in mid-to-late pregnancy. Spearman correlation analysis was conducted to examine the correlation between EPDS scores and fNIRS imaging features， as well as demographic characteristics， in mid-to-late pregnant women with depression. Multiple linear regression was used to analyze the influencing factors of depression symptoms in this population. ResultsStatistically significant differences were observed between the study group and the control group in terms of educational level and body mass index （BMI） （χ²/t=4.528， 2.292， P<0.05）. The study group demonstrated a lower prefrontal integral value and a higher prefrontal center of gravity value compared with the control group （t=-7.601， 5.641， P<0.05）. EPDS scores of depressed pregnant women in mid-to-late pregnancy were negatively correlated with prefrontal lobe integral value （r=-0.680， P<0.01）， while positively correlated with prefrontal lobe center of gravity value and BMI （r=0.737， 0.604， P<0.01）. Multiple linear regression analysis showed that age （β=-0.214， P<0.01）， BMI （β=0.340， P<0.01）， prefrontal integral value （β=-0.351， P<0.01）， and prefrontal center of gravity value （β=0.347， P<0.01） were influencing factors of depressive symptoms in pregnant women in mid-to-late pregnancy. ConclusionThe prefrontal lobe activation degree of depressed pregnant women in mid-to-late pregnancy is lower than that of non-depressed pregnant women， and the activation phase is delayed. Age， prefrontal lobe integral value， prefrontal center of gravity value and BMI may be the influencing factors of depressive symptoms in pregnant women in the middle and late pregnancy.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Objective:To investigate the clinical value of Delphian lymph node (DLN) metastasis (DLNM) in predicting regional lymph node involvement in patients with intrathyroidal papillary thyroid carcinoma (PTC).Methods:Clinical and pathological data from 345 consecutive patients with pathologically confirmed DLN status, who underwent initial surgical treatment at the Department of Surgical Oncology, First Affiliated Hospital of Zhejiang University School of Medicine between Jan 2020 and Dec 2022, were retrospectively analyzed.Results:DLNM was identified in 61 patients (17.7%). Univariate analysis revealed significant associations between DLNM and male sex, elevated preoperative thyroglobulin levels, larger tumor size, maximum tumor diameter >10 mm, bilateral lesions, multifocality, lymphovascular invasion, and lymph nodes metastases in pretracheal, paratracheal, and lateral cervical(all P ≤0.001). Elevated thyroglobulin antibody levels ( χ2=6.201, P=0.013) and Hashimoto's thyroiditis ( χ2=11.340, P<0.001) were protective factors for DLNM. Multivariate analysis identified male sex, lymphovascular invasion, pretracheal, and paratracheal lymph node metastases ( χ2=6.689, P=0.010; χ2=8.163, P=0.004; χ2=7.605, P=0.006; χ2=8.324, P=0.004) as independent risk indicators for DLNM. Patients with DLNM exhibited significantly higher risks of lymph nodes metastases in pretracheal ( χ2=27.307, P<0.001), paratracheal ( χ2=38.697, P<0.001), and lateral cervical ( χ2=36.459, P<0.001). Conclusion:DLNM demonstrates predictive value for both central compartment and lateral cervical lymph node metastases, warranting particular attention to meticulous dissection of the prelaryngeal region during surgery.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To establish a combined model of spectral CT multi-parameters and clinical features to distinguish between gastric poorly cohesive carcinoma and tubular adenocarcinoma.Methods A total of 87 patients with gastric cancer confirmed by postoperative pathology were retrospectively selected,including 26 patients with poorly cohesive carcinoma and 61 patients with tubular adenocarcinoma.Predictors were identified by univariate and multivariate logistic regression analyses,and a combined model was established.The area under the curve(AUC)of receiver operating characteristic(ROC)curve was used to evaluate the differential diagnostic efficiency of the parameters and the model.The AUC was compared by DeLong method.Results The gender[odds ratio(OR)5.124,P=0.004],normalized iodine density in the arterial phase(nIoDAP)(OR 5.789,P=0.017),arterial enhancement fraction(AEF)(OR 7.007,P=0.002)and ΔIoD(OR 0.025,P=0.021)were identified as independent predictors for poorly cohesive carcinoma by logistic regression analysis.The AUC of combined model established by four variables in distinguishing poorly cohesive carcinoma and tubular adenocarcinoma was 0.837[95％confidence interval(CI)0.716-0.907],which was significantly higher than that of single tumor spectral CT parameters(P＜0.01).Conclusion The combined model based on patients'gender and tumor spectral CT parameters(nIoDAP,AEF and ΔIoD)can effectively distinguish gastric poorly cohesive carcinoma and tubular adenocarcinoma,providing a basis for gastric cancer patients'individualized treatment strategy.

Objective:To construct a calcium alginate (ALG-Ca 2+) composite hydrogel loaded with chlorella protein (Cp) (ALG-Ca 2+@Cp) and investigate its combined effect with microwave hyperthermia on the proliferation, apoptosis, and immune activation of mouse pancreatic cancer cells. Methods:ALG-Ca 2+@Cp was prepared using a physical cross-linking method and its physiochemical properties was characterized via scanning electron microscopy, rheological analysis, Ca 2+ release experiments, and microwave thermal conversion tests. The BCA protein quantification assay was used to evaluate the adsorption capacity of ALG-Ca 2+@Cp for pancreatic cancer cell antigens. The effects of ALG-Ca 2+@Cp extract combined with microwave intervention on pancreatic cancer cell proliferation, apoptosis protein expression, and cell viability were assessed using CCK-8 assays, ELISA, and Calcein-AM/PI double fluorescence staining. Flow cytometry was performed to determine the maturation-promoting ability of ALG-Ca 2+@Cp on immature mouse bone marrow-derived dendritic cells (BMDCs). Results:ALG-Ca 2+@Cp exhibited a three-dimensional network structure with a storage modulus (G') greater than the loss modulus (G''), demonstrating typical hydrogel properties. The hydrogel loaded with 0.5 mol/ml Ca 2+ reached 48°C after 5 minutes of microwave irradiation at 5.0 W/cm 2, and Ca 2+ release plateaued within 5 minutes. ALG-Ca 2+@Cp effectively adsorbed pancreatic cancer cell antigens. Combined with microwave treatment, it significantly reduced pancreatic cancer cell proliferation ( A450 value 0.39±0.07 vs 2.78±0.15) and increased apoptosis markers calreticulin (CRT) and high mobility group box-1 protein (HMGB1) [(557.09±37.84) pg/ml vs (135.14±11.84) pg/ml, (4.77±0.18) ng/ml vs (1.6±0.16) ng/ml], leading to decreased cell viability; and all the differences were statistically significant (all P value <0.05). ALG-Ca 2+@Cp synergistically promoted the maturation of immature BMDCs in the presence of pancreatic cancer antigens, with a CD 80+ positivity rate of (75.67±6.53)%. Conclusions:ALG-Ca 2+@Cp is successfully constructed. Its combination with microwave hyperthermia can significantly enhance the cytotoxicity and immune activation against mouse pancreatic cancer cells by targeting intracellular antigens and inducing immunogenic cell death.

The incidence of bile duct stones, as a prevalent disorder of digestive system, has been increasing annually. Challenges such as high recurrence rates, management of complex cases, and applicability in specific populations remain in clinical practice. Endoscopic retrograde cholangiopancreatography (ERCP), renowned for its precise localization and efficient stone removal, has long been regarded as the first-line treatment for choledocholithiasis. However, the limitations of traditional X-ray-guided ERCP have spurred ongoing innovations in its technology, which is an art of balance between " preserving tradition" and " embracing innovation". This work systematically reviewed the evolution and breakthroughs of ERCP and its derivative techniques in the diagnosis and treatment of bile duct stones, with a focus on advances in the radiation-free ERCP and cholangioscopy-guided lithotripsy. Additionally, it addresses diagnostic methods for bile duct stones complicated by strictures, ERCP strategies for concurrent bile duct and gallbladder stones, and novel approaches to preserving the duodenal papilla. Nevertheless, the adoption of these innovations remains constrained for procedural complexity, equipment costs, and expertise of operator. Future efforts should emphasize the multidisciplinary collaboration, technical standardization, and optimization of devices to greater precision and less invasiveness in ERCP, making it more applicable to diverse clinical scenarios, and ultimately achieving comprehensive progress in personalized management of bile duct stones.