ObjectiveTo evaluate whether the use of intrapartum ultrasound （IPUS） to monitor the labor process， as alternative method of traditional vaginal examination （VE）， could reduce the incidence of postpartum complications associated with vaginal delivery. MethodsA total of 360 primiparas who underwent cervical dilation balloon induction of labor （IOL） and achieved successful vaginal delivery after childbirth at the Third Affiliated Hospital of Sun Yat-sen University between January 2022 and December 2023， were included in the retrospective study with half assessed for labor progress using IPUS （n=180） and the other half using VE （n=180）. The differences in the relevant indicators of the labor process and the complications of vaginal delivery were compared between the two groups of pregnant women. ResultsThere was no significant difference in the duration of membrane rupture， the first stage of labor and the second stage of labor between the two groups. However， the number of VE in the IPUS group was significantly lower ［nulliparous： 4 （3-4） vs. 6 （5-8）， P＜0.001； multiparous： 2 （2-3） vs. 4 （3-5）， P＜0.001］. The IPUS group experienced a lower incidence of postpartum fever compared to the VE group ［1.67%（3/180） vs. 7.22%（13/180）， P=0.006］， while other complications of vaginal delivery， such as fever during labor， postpartum hemorrhage （PPH）， laceration， poor wound healing and uroschesis， were not significantly different （all P ＞ 0.05）. The logistic regression analysis confirmed that the use of IPUS served as a protective factor for postpartum fever with an OR of 0.06 ［95% CI （0.01， 0.36）； P=0.002］， while the duration of membrane rupture was a risk factor ［OR： 1.12； 95% CI （1.03， 1.22）； P = 0.011］. ConclusionsIPUS， as an alternative to traditional VE， does not affect the progress of labor. However， it can significantly reduce the frequency of VE and the incidence of postpartum fever， thereby facilitating the rapid recovery of postpartum women， which makes it clinically valuable for application.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

ObjectiveTo investigate the perceived experience and acceptance of intrapartum ultrasound （IPUS） as a novel method for labor progress assessment among pregnant women. MethodsFrom February 2023 to December 2024， a total of 180 pregnant women admitted to the Labor Ward of Lingnan Hospital， the Third Affiliated Hospital of Sun Yat-sen University， who were planned for vaginal trial of labor ， were accessed for labor progress using IPUS and vaginal examination （VE） after the onset of labor and prior to the initiation n of labor analgesia. A self-designed questionnaire was used to investigate the women's perceived experiences with both examination methods and their acceptance of IPUS. The pain intensity associated with the examinations was evaluated using the visual analogue pain scale （VAS）. Differences in the women's experiences and pain intensity between the two labor progress assessment methods were compared. ResultsThe acceptance rate of IPUS was 96.67% （174/180）， with the remaining 6 cases undecided. Over 60% of the pregnant women reported IPUS assessment as comfortable and none of them felt discomfort， whereas 32.8% felt uncomfortable with VE （χ²=196.02， P＜0.001）. Nearly two-thirds of the pregnant women believed that VE would cause psychological distress， while none reported such effect with IPUS （χ²=261.52， P＜0.001）. Approximately 77.78% （140/180） of the pregnant women believed that IPUS could reduce their fear of vaginal delivery and enhance their confidence if it replaced VE. The VAS score for IPUS ［0 （0， 2）］ was significantly lower than that for VE ［4 （4， 6）］ （Z=-14.62， P＜0.001）. Further stratified analysis showed that over 90% （164/180） of the pregnant women found IPUS painless， with no moderate or severe pain reported， compared to 43.33% （78/180） experienced moderate or severe pain with VE （P＜0.001）. ConclusionAs a novel approach for labor progress assessment， IPUS not only alleviates the pain and discomfort associated with traditional VE and reduces the fear of childbirth but also enhances women's confidence in delivery， thereby achieving a high level of acceptance among parturient women in China.

Endotoxins are common exogenous pyrogens. Excessive endotoxins in medical devices and injections can lead to serious consequences such as sepsis, septic shock, and even death. Therefore, endotoxin detection plays a crucial role in medical, pharmaceutical, and food sectors. The wide application of Limulus amebocyte lysate (LAL) has led to a sharp decline in the number of horseshoe crabs. Moreover, the LAL assay has limitations such as interbatch variations and difficulty in quantification. The recombinant factor C (rFC) assay is stable between batches, highly sensitive, and capable of quantitation, and thus it can be used as an alternative for the LAL assay. However, the high cost and complex procedures involved in producing recombinant factor C have limited the widespread application of this method. In order to simplify the preparation and reduce the production cost of recombinant factor C, this study focuses on the production of recombinant factor C based on the baculovirus expression system. Multiple measures such as a high-yield and anti-apoptotic vector qBac-IIIG, the optimal signal peptide, and the optimized codon were used to reach the goal of endotoxin detection with cell supernatant. This method simplifies the steps of protein purification. The sensitivity of the supernatant reached 0.05 EU/mL in a 1-L fermentation system, and 500 000 detecting reactions can be supported per liter of fermentation broth. This study increases the yield and activity of recombinant factor C, simplifies the procedures of protein purification, and reduces the cost, laying a foundation for the promotion and application of recombinant factor C in endotoxin detection.
Animals ; Recombinant Proteins/genetics* ; Horseshoe Crabs/chemistry* ; Baculoviridae/metabolism* ; Endotoxins/analysis* ; Protein C/biosynthesis* ; Genetic Vectors/genetics* ; Arthropod Proteins/genetics* ; Enzyme Precursors ; Serine Endopeptidases

Background::Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3 + and CD8 + T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3 CT (CD3 + T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology. Methods::The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted.Results::The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3 CT and CD3-CD8 (the combination of CD3 + and CD8 + T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3 CT was confirmed as an independent prognostic factor, with high CD3 CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12–0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05–0.92, P = 0.037). Conclusions::We quantify the spatial distribution of CD3 + and CD8 + T cells within tissue regions in WSIs using AI technology. The CD3 CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3 CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

Objective To investigate the risk factors of pancreatic pseudocysts(PPC) in patients with acute pancreatitis (AP) in a retrospective cohort study. Methods 460 AP patients with complete follow-up data admitted in Affiliated Hospital of Qingdao University from January 2004 to March 2012 were retrospectively analyzed,who were divided into PPC group and control group. Age,gender,body mass index(BMI),history of diabetes,etiology,the presence of ascites and hydrothorax,the presence of abdominal mass,the presence of acute fluid collection, APACHEⅡ score at 48 h admission, CT severity index (CTSI), serum albumin, amylase,LDH,ALP, BUN, Cr, TG, TB, conjugated bilirubin, CRP, serum calcium and other laboratory markers were recorded. Univariate logistic regression analysis was used to select the factors that were statistically different between two groups, and multivariate logistic regression analysis was performed to determine the independent risk factors for AP complicated with PPC. Results 143(31.1%) of 460 AP patients developed PPC. On univariate analysis, a total of 11 factors including male sex, BMI ≥28 kg/m2, history of diabetes, alcoholic pancreatitis, ascites, pleural effusion, palpable abdominal mass, acute fluid collections,APACHEⅡscore,CTSI≥7 and serum albumin were statistically different between two groups. On multiple logistic regression analysis, it was shown that male sex (OR 3.23, 95% CI 1.560~ 6.301, P=0.03),history of diabetes (OR 2.23,95% CI 1.021~3.920,P=0.04), ascites (OR 1.62,95% CI 0.652~2.432, P=0.01), pleural effusion (OR 2.43, 95% CI 1.201~7.201, P=0.03), a palpable abdominal mass(OR 1.83,95% CI 0.737~4.320,P<0.001) and CTSI≥7(OR 5.12,95% CI 1.890~14.012, P<0.001) were independent risk factors significantly associated with the PPC formation. Conclusions The male sex, diabetic history, ascites, pleural effusion, palpable abdominal mass and high CTSI score were the independent risk factors of PPC formation in AP.

Objective To investigate the expression of BAMBI in pancreatic carcinoma tissue and its clinical value.Methods Expression of BAMBI was detected by immunohistochemistry in 69 cases of pancreatic cancer and 15 normal pancreatic samples.The survival and its association with clinicopathologic parameters were analyzed.Results The expression of BAMBI in the cancer tissue was much higher than that in the normal tissues (56.5％ vs 16.7％,P ＜0.01).The expression of BAMBI was not associated with age,sex and tumor size,differentiation,but expression of BAMBI in patient with lymph node metastasis was higher than that in patient without lymph node metastasis (67.4％ vs 38.5％,P =0.019),the expression of BAMBI in TNM stage Ⅲ was higher than that in stage Ⅰ + Ⅱ (75.0％ vs 31.0％,P =0.001).The median survival of BAMBI-positive group (6 months) was lower than that of BAMBI-negative group (10 months).Conclusions BAMBI is over-expressed in pancreatic carcinoma,and its expression is associated with lymph node metastasis,TNM staging,differentiation and prognosis.

Cell-free protein expression system is a new method to express target protein in vitro and has been widely applied to the study of protein structure, protein function and other related fields. Preparation of cell extract is one of the key factors that affect the efficiency of the cell-free system. To improve the efficiency and economical feasibility of cell-free protein synthesis, we discussed the parameters during the preparation of the cell extract. These parameters include centrifugation speed, pre-incubation, and dialysis. We used the green fluorescent protein as the reporter protein, and obtained a simple procedure for the preparation of Escherichia coli cell extract. A simple centrifugation step (12 000 x g, 10 min) followed by a brief incubation was sufficient for the preparation of an active cell extract to support protein expression with higher productivity (209 microg/mL). Compared to the traditional E. coli S30 procedure, the processing time was reduced by 62%, and the productivity was increased by 2.6 times. The new procedure will make the advantage of cell-free technology more obvious, and promote its wider application.
Cell Fractionation ; methods ; Cell-Free System ; Escherichia coli ; cytology ; genetics ; metabolism ; Escherichia coli Proteins ; biosynthesis ; chemistry ; isolation & purification ; Green Fluorescent Proteins ; metabolism

[Objective] To explore the clinical pathological characteristics and treatment of pancreatic careinoid. [Methods] Eight patients with pancreatic careinoid were recruited between January in 1997 and December in 2007 for retrospective analysis which involved tumor markers, inanunohistostaining, accompanied with other tumors, misdiagnosis, metastasis, in-hospital mortality rate, and so on. The relevant literatures were simultaneously reviewed to comprehend the clinical pathological characteristics of pancreatic carcinoid. [Results] Tumor markers CEA, CA199, CA125, and CA72-4 in pancreatic carcinoid were 0%, 25%, 12.5%, and 0%, respectively. Specimen immanohistostaining Syn, CgA, NSE, and CK in pancreatic carcinoid were 25%, 62.5%, 75%, and 75%, respectively. Two pancreatic carcinoids were accompanied by other tumors in 8 cases. The misdiagnosis rate of pancreatic carcinoid (7/8) was markedly high. Pancreatic carcinoid possessed high metastasis (50%), high in-hospital mortality rate (37.5%) and low radical operation undergone (62.5%). [Conclusions] Pancrcatic carcinoid was accompanied with high misdiagnosis rate and poor prognosis. Routine sero-markers did not help discover pancreatic carcinoid early. The final diagnosis depended on specimen immunohistostaining with Syn, CgA, NSE, and CK.

Objective To explore the effects of ecoimmunonutrition support on the intestinal barrier function and pancreas in rats with severe acute pancreatitis (SAP). Methods Totally 64 SPF rats were randomly divided into sham operation group (control group) , SAP without enteral nutrition support group (SAP group), SAP with early enteral nutrition support group (EEN group), and SAP with early ecoimmunonutrition support group (EIN group). Bacteria translocation (BT), plasma endotoxin (ET) , gut permeability, pancreas pathology score,and distant ileum pathology were determined on the 4th and 7th post-modeling day. Results The BT rate was significantly higher in SAP group, EEN group, and EIN group than in control group (P ＜ 0.05), was significantly lower in EEN group and EIN group than in SAP group (P ＜ 0.05), and was significantly lower in EIN group than in EEN group (P ＜ 0.05). ET and FD-40 levels in blood were both significantly higher in SAP group, EEN group, and EIN group than in control group (P ＜0.01)and were significantly lower in EIN group and EEN group than in SAP group (P ＜0.01); ET was significantly lower in EIN group than in control group (P ＜0.05). Pathological scores were significantly higher in SAP group, EEN group, and EIN group than in control group (P ＜0.01)and were significantly lower in EEN group and EIN group than in SAP group (P ＜ 0.01). The individual pathological scores of EIN group were not significantly different from EEN group (P ＞ 0.05), while the total score was significantly lower in EIN group than in EEN group (P ＞ 0.05). Distant iliac mucosa was significantly thicker in EIN group than in other groups. Conclusions Early enteral nutrition support protects the intestinal barrier and pancreas in rats with SAP. Ecoimmunonutrition has better nutritional effectiveness than the normal enteral nutrition.