[Study on the relationship between hemoglobin glycosylation index and arteriosclerosis- related blood lipids].

Objective: To study the relationship between hemoglobin glycation index (HGI) and blood lipid indices such as low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and plasma atherogenic index (AIP). Methods: This cross-sectional study included 16 049 participants from the Beijing Apple Garden community between December 2011 and August 2012. The subjects were divided into three groups based on the HGI quartile: low (n=5 388), medium (n=5 249), and high (n=5 412). The differences in blood lipid indicators between different HGI groups were compared and multivariate logistic regression model was established to analyze the association between HGI and dyslipidemia. And multivariate logistic regression model was established to analyze the relationship between HGI and blood lipid indicators in different glucose metabolism populations. Results: There were 16 049 participants in all (mean age: 56 years), including 10 452 women (65.1%). They were classified into normal glucose tolerance (9 093 cases), prediabetes (4 524 cases), and diabetes (2 432 cases) based on glucose tolerance status. In the general population, with the increase of HGI, LDL-C, non-HDL-C, and AIP gradually increased (all P values for trends were <0.05), and the proportion of abnormalities increased significantly (χ2=101.40, 42.91, 39.80; all P<0.001). A multivariate logistic regression model was established, which suggested a significant correlation between HGI and LDL-C, non-HDL-C, and AIP (all P<0.05), after adjusting for factors such as age, sex, fasting blood glucose, hypertension, body mass index, smoking, and alcohol consumption. In the overall population, normal glucose tolerance group, and diabetes group, HGI had the highest correlation with non-HDL-C (OR values of 1.325, 1.678, and 1.274, respectively); in the prediabetes group, HGI had a higher correlation with LDL-C (OR value: 1.510); and in different glucose metabolism groups, AIP and HGI were both correlated (OR: 1.208-1.250), but not superior to non-HDL-C and LDL-C. Conclusion: HGI was closely related to LDL-C, non HDL-C, and AIP in the entire population and people with different glucose metabolism, suggesting that HGI may be a predictor of atherosclerotic cardiovascular disease.

Accuracy of patient-specific implants versus CAD/CAM splints with the mandible-first approach in bimaxillary orthognathic surgery for skeletal Class II malocclusion.

This retrospective study aimed to compare the accuracy of patient-specific implants (PSI) versus mandible-first computer-aided design and manufacturing (CAD/CAM) splints for maxilla repositioning in orthognathic surgery of skeletal Class II malocclusion patients. The main predictor was the surgical method (PSI vs. splints), with the primary outcome being the discrepancy in maxilla centroid position, and secondary outcomes being translation and orientation discrepancies. A total of 82 patients were enrolled (70 female, 12 male; mean age 25.5 years), 41 in each group. The PSI group exhibited a median maxillary position discrepancy of 1.25 mm (interquartile range (IQR) 1.03 mm), significantly lower than the splint group's 1.98 mm (IQR 1.64 mm) (P < 0.001). In the PSI group, the largest median translation discrepancy was 0.74 mm (IQR 1.17 mm) in the anteroposterior direction, while the largest orientation discrepancy was 1.83° (IQR 1.63°) in pitch. In the splint group, the largest median translation discrepancy was 1.14 mm (IQR 1.37 mm) in the anteroposterior direction, while the largest orientation discrepancy was 3.03° (IQR 2.11°) in pitch. In conclusion, among patients with skeletal Class II malocclusion, the application of PSI in orthognathic surgery yielded increased precision in maxillary positioning compared to mandible-first CAD/CAM splints.

[The Miao medicine Sidaxue alleviates rheumatoid arthritis in rats possibly by downregulating matrix metalloproteinases].

OBJECTIVE: To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1ß levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. RESULTS: Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1ß, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. CONCLUSION: Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1ß/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.

[The clinical features, survival analysis, and geriatric assessment of 85 patients with follicular lymphoma: a single-center study].

Objective: To retrospectively analyze the clinical characteristics and prognosis of 85 newly diagnosed patients with follicular lymphoma (FL), as well as the prognostic value of comprehensive geriatric assessment (CGA) in patients with FL aged ≥ 60 years old. Methods: The clinical data and prognosis of 85 newly diagnosed FL patients admitted from August 2011 to June 2022 were collected. The clinical features, laboratory indicators, therapeutic efficacy, survival and prognostic factors of patients were statistically analyzed, and the prognosis of patients was stratified using various geriatric assessment tools. Results: ① The patients with FL were mostly middle-aged and older, with a median age of 59 (20-87) years, including 41 patients (48.2%) aged ≥60 years. The ratio of male to female was 1∶1.36. Overall, 77.6% of the patients were diagnosed with Ann Arbor stage Ⅲ-Ⅳ, and 17 cases (20.0%) were accompanied by B symptoms. Bone marrow involvement was the most common (34.1%). ②Overall, 71 patients received immunochemotherapy. The overall response rate was 86.6%, and the complete recovery rate was 47.1% of 68 evaluated patients. Disease progression or relapse in the first 2 years was observed in 23.9% of the patient. Overall, 14.1% of the patients died during follow-up. ③Of the 56 patients receiving R-CHOP-like therapies, the 3-year and 5-year progression-free survival (PFS) rates were 85.2% and 72.8%, respectively, and the 3-year and 5-year overall survival (OS) rates were 95.9% and 88.8%, respectively. The univariate analysis showed that age ≥60 years old (HR=3.430, 95% CI 1.256-9.371, P=0.016), B symptoms (HR=5.030, 95% CI 1.903-13.294, P=0.016), Prognostic Nutritional Index (PNI) <45.25 (HR=3.478, 95% CI 1.299-9.310, P=0.013), Follicular Lymphoma International Prognostic Index (FLIPI) high-risk (HR=2.918, 95% CI 1.074-7.928, P=0.036), and PRIMA-prognostic index (PRIMA-PI) high-risk (HR=2.745, 95% CI 1.057-7.129, P=0.038) significantly predicted PFS. Moreover, age ≥60 years old and B symptoms were independent risk factors for PFS. Progression of disease within 24 months (POD24) significantly predicted OS in the univariate analysis. Conclusions: FL is more common among middle-aged and older women. Age, B symptoms, PNI score, FLIPI high-risk, PRIMA-PI high-risk, and POD24 influenced PFS and OS. The CGA can be used for treatment selection and risk prognostication in older patients with FL.

[Comparison of surgical outcomes between Kahook Dual Blade goniotomy and Trabectome surgery in patients with open-angle glaucoma].

Objective: To compare the medium-term therapeutic effects of Kahook Dual Blade (KDB) goniotomy and Trabectome surgery in the treatment of patients with primary open-angle glaucoma (POAG). Methods: This study was a non-randomized prospective interventional controlled clinical study. POAG patients who underwent KDB goniotomy or Trabectome surgery at Beijing Tongren Hospital from May 2017 to April 2022 were enrolled. The definition of successful surgery was postoperative average intraocular pressure (IOP)≤21 mmHg (1 mmHg=0.133 kPa) and IOP decrease≥20%. Follow-up visits were conducted on the 1st day, 1st week, 1st, 3rd and 6th month after surgery. The IOP value, the number of IOP-lowering medications, the proportion of surgical success (average IOP≤21 mmHg at 6 months), and complications were evaluated. Statistical methods included independent sample t-test, Mann-Whitney rank sum test, χ2 test, repeated measures two-factor analysis of variance, Bonferroni, Friedman M test, Wilcoxon, and Log-rank. The Kaplan-Meier method was used to calculate the cumulative success rate of each group. Results: Seventeen male patients (17 eyes) and 10 female patients (10 eyes) were included. The mean age was (39.9±17.7) years old. There were 11 patients in the KDB group and 16 patients in the Trabectome group. There was no significant difference in clinical baseline conditions between the two groups (P>0.05). The IOPs in the KDB and Trabectome groups at postoperative 1 week [(16.6±6.3) and (16.4±4.1) mmHg) and 6 months [(17.8±5.3) and (19.9±4.4) mmHg) were lower than those before surgery [(25.1±9.3) and (27.4±9.1) mmHg) (all P<0.05). There was no significant difference in the overall IOP between groups (P>0.05). The IOP reduction rates in the KDB and Trabectome groups were 23.4% and 19.0%, with no significant difference (P=0.674). The numbers of IOP-lowering medications used in the KDB and Trabectome groups at 3 months [2.0 (1.0, 4.0) and 2.0 (1.0, 2.3)] and 6 months [2.0 (0.0, 4.0) and 2.0 (1.0, 3.0)] after surgery were not significantly different from those before surgery [4.0 (2.0, 4.0) and 3.0 (2.0, 4.0)] (both P>0.05). There was no statistical significance in the overall number of IOP-lowering medications used between the two groups (P>0.05). There was also no statistically significant difference in the proportion of patients with an IOP decrease of≥20% and the proportion of patients whose mean postoperative IOP was≤21 mmHg (all P>0.05). The proportions of IOP≤21 mmHg in the KDB group and the Trabectome group at 6 months after surgery were 81.8% and 68.8% (P>0.05). Serious intraoperative or postoperative complications occurred in neither group. Conclusions: Both KDB trabeculotomy and Trabectome surgery can effectively reduce IOP and have a good safety profile in treating POAG, with the same number of IOP-lowering medications.

Exploring the role of histone deacetylase inhibitors in cancer development and therapeutic potential.

The process of acetylation and deacetylation of histones within the nucleus operates within a dynamic equilibrium. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) collaboratively and precisely regulate normal gene transcription and expression. Any disorder in the activity of HATs/HDACs can lead to uncontrolled gene expression, consequently resulting in tumorigenesis. Histone deacetylase inhibitors (HDACIs) have the capacity to block the cell cycle, thereby restraining tumor cell proliferation and tumor growth. Also, HDACIs exhibit a significant capability to diminish the expression of apoptosis protein inhibitors such as Bcl-2 and B-cell lymphoma-extra-large (Bcl-xL), while concurrently up-regulating pro-apoptotic proteins such as Bax, Bad, and Bim. Also, HDACIs demonstrate the ability to inhibit tumor cell angiogenesis. Representing a new category of targeted anti-cancer therapeutics, HDACIs possess the capability to restore the expression of tumor suppressor genes, induce apoptosis, and stimulate cell differentiation. Additionally, they exert anti-cancer effects through diverse pathways both in vivo and in vitro, thereby presenting promising prospects in tumor therapy. This review delves into the involvement of HDACs in cancer pathology and the therapeutic potential of HDACIs as emerging drugs in cancer treatment.

[The preliminary application of mNGS in the diagnosis of invasive fungal sinusitis].

Objective: By conducting a retrospective analysis of the clinical data of 14 patients diagnosed with invasive fungal rhinosinusitis (IFRS) confirmed by metagenomics next generation sequencing (mNGS) technology, we aim to explore the rapid diagnosis value of mNGS in IFRS. Methods: The clinical data of 14 IFRS patients admitted to TianJin First Central Hospital were retrospectively analyzed from February 2021 to October 2023. The study cohort comprised 8 males and 6 females, with ages ranging from 14 to 77 years. All patients were diagnosed as IFRS by performing mNGS sequencing technology of nasal sinus lesion biopsy specimens. Clinical data such as laboratory examination, imaging examination, histopathological examination results, treatment plan and prognosis were summarized and analyzed. Results: All 14 patients were diagnosed as IFRS, with mNGS detecting pathogens such as Rhizopus (7 cases), Aspergillus (5 cases), Trichoderma (1 case), and Scedosporium apiospermum (1 case). Follow-up evaluations were conducted for a period ranging from 2 months to 2 years post-treatment. At the end of follow-up, 11 out of 14 IFRS patients achieved a complete cure with no signs of recurrence, while the symptoms of the remaining 3 patients significantly improved with comprehensive treatment. Conclusion: mNGS emerges as a highly effective diagnostic tool for IFRS, providing valuable microbiological evidence for clinical diagnosis and demonstrating promising clinical utility.

[Preparation of a dual-specific antibody targeting human CD123 and exploration of its anti-acute myeloid leukemia effects].

Objective: To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) . Methods: Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified. Results: ① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123(+) tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group (P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10(5)/ml to 3.2×10(6)/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8(+) PD-1(+) LAG-3(+) T cells was 10.90%, and the proportion of propidium iodide (PI) (-) Annexin Ⅴ(+) T cells and PI(+) Annexin Ⅴ(+) T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group (P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group (P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group (P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123(+) tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123(+) MV4-11 cells, CD123(+) Molm13 cells, and CD123(+) THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group (P<0.05) . Conclusion: In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123(+) tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

[Analysis of the application effect and safety of transnasal humidified rapid insufflation ventilatory exchange technique in hysteroscopic diagnostic and therapeutic surgery].

Objective: To investigate the effect and safety of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) technique in hysteroscopic diagnostic and therapeutic surgery. Methods: This study was a randomized controlled trial. A total of 100 female patients undergoing hysteroscopy surgery at Beijing Tongren Hospital from September to December 2023 were selected and randomly divided into two groups by the random number table method: the THRIVE group and the mask oxygen group, with 50 patients in each group. Patients in both groups were given total intravenous anesthesia with propofol combined with remifentanil and preserved spontaneous respiration. The THRIVE group was given oxygen by the THRIVE device with an oxygen flow rate of 50 L/min, while the mask oxygen group was given oxygen by the mask with an oxygen flow rate of 5 L/min; the oxygen concentration of both groups was set at 100%. The general condition of the patients, vital signs during the operation, the amount of anesthesia drugs used and the operation time were recorded. The primary observation index was the incidence of hypoxic events in the two groups; the secondary observation indexes were the incidence and time of intraoperative apnea as well as the corresponding oxygenation interventions and the incidence of non-hypoxic adverse events. Results: The age of the THRIVE group was (42±14) years, and the age of the mask oxygen group was (43±15) years. The duration of surgery in the THRIVE group was (15.9±3.4) min, which was statistically lower than that of the mask oxygen group (16.3±4.5) min (P=0.041), and there were no differences observed in the duration of awakening time and anesthesia time (both P>0.05). There was no significant difference in the dosage of propofol, remifentanil, and intraoperative vasoactive drugs between the two groups (all P>0.05). The SpO2 of the patients in the THRIVE group at the end of the operation was (99.7±1.1) %, which was higher than that of the mask-oxygen group (99.1±1.1) % (P<0.05). There was no difference in SpO2 of the two groups at the other time points (all P>0.05). There were no differences in HR and MAP of two group patients at each time point (all P>0.05). The incidence of hypoxic events in the THRIVE group was 12.0% (6/50), which was lower than that of 28.0% (14/50) in the mask oxygen group (P=0.045). The difference in the incidence and duration of apnea between the two groups was not statistically significant (all P>0.05). There were no cases of temporary need for laryngeal mask or tracheal intubation during surgery in both groups. There was no statistically significant difference in the incidence of intraoperative body movement, dizziness, nausea and vomiting between the two groups (all P>0.05), and no cardiac, cerebral, renal or other important organ insufficiency occurred in the two weeks after surgery. Conclusion: THRIVE technology can provide effective oxygenation for patients undergoing hysteroscopic diagnosis and treatment, maintain patients' circulatory stability, and improve the safety and efficiency of surgery.

[Clinical analysis of 9 children with refractory N-methyl-D-aspartate receptor antibody encephalitis children treated with tocilizumab].

Objective: To analyze the clinical features of children with refractory N-methyl-D-aspartate (NMDA) receptor antibody encephalitis treated with tocilizumab. Methods: Demographic and clinical manifeatations, immunotherapy and prognosis data of 9 children with refractory NMDA receptor antibody encephalitis who received tocilizumab in the Department of Pediatrics Neurology, XiangYa Hospital of Central South University from August 2021 to September 2023 were collected retrospectively. Prognosis was evaluated using the modified Rankin scale at initial diagnosis, at the initiation of tocilizumab treatment, and at the last follow-up. Treatment related complications, neuroimaging, and electroencephalography data were analyzed. Results: Among the 9 children, 6 were male and 3 were female, with an onset age of 4.2 (2.8, 8.7) years. At the onset of the disease, 9 children had a modified Rankin scale score of 5. When tocilizumab treatment was initiated, 7 children had a score of 5, and 2 children had a score of 4. The interval between the onset and initiation of tocilizumab treatment was 12 (5, 27) months, and the treatment frequency was 8 (5, 13) times. The follow-up time was 2.8 (1.5, 3.7) years. At the last follow-up, the symptoms of 9 children, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction, were improved to varying degrees, and none of them had seizures. At the last follow-up, 4 cases with a modified Rankin scale score of 0, 1 case with a score of 1, 2 cases with a score of 3, 1 case with a score of 4 and 1 case with a score of 5. The modified Rankin scale at the last follow-up was significantly different from that at the start of tocilizumab (Z=-2.56, P=0.014). All children had no serious adverse reactions during the treatment. Conclusions: After treatment with tocilizumab, the symptoms in patients with refractory NMDA receptor antibody encephalitis, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction were improved, and none of them had seizures. The modified Rankin scale were improved, and the safety was good.

Classification of breast edema on T2-weighted imaging for predicting sentinel lymph node metastasis and biological behavior in breast cancer.

OBJECTIVE: To determine whether preoperative classification of breast edema on T2-weighted imaging (T2WI) is useful for predicting sentinel lymph node (SLN) metastasis and biological behavior in patients with early-stage breast cancer. METHODS: This retrospective study involved 341 women with breast cancer who underwent breast MRI from January 2019 to March 2022. Breast edema was scored on a scale of 1-4 on T2WI (1, no edema; 2, peritumoral edema; 3, prepectoral edema; and 4, subcutaneous edema). A logistic regression model was employed for univariate and multivariate analyses. A clinicopathological model was established using independent influencing factors identified in the multivariate analyses, excluding breast edema score (BES). Subsequently, BES was incorporated into this model to establish a combined BES model. The AUC and Delong test were used to examine the additional predictive value of the BES. RESULTS: Logistic regression analysis showed that breast edema was an independent risk factor for SLN metastasis. The combined BES model significantly improved the predictive performance of SLN metastasis compared with the clinicopathological model alone (AUC, 0.77 vs. 0.71; p=0.005). In addition, the BES was significantly positively correlated with the tumor diameter (p<0.001), histologic grade (p=0.001), Ki-67 index (p<0.001), and non-luminal subtypes (p<0.001). CONCLUSION: The BES on T2WI is useful for predicting SLN metastasis. A higher grade of breast edema is associated with breast cancer aggressiveness and increases the probability of SLN metastasis.

[Upregulating KLF11 ameliorates intestinal inflammation in mice with 2, 4, 6-trinitrobenesulfonic acid-induced colitis by inhibiting the JAK2/STAT3 signaling pathway].

OBJECTIVE: To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. METHODS: We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2, 4, 6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. RESULTS: The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P < 0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P < 0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P < 0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P < 0.05). CONCLUSION: KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.

[Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis].

OBJECTIVE: To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. METHODS: C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. RESULTS: Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = -3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = -0.723, P > 0.05), TNF-α (t = -0.659, P > 0.05), IL-4 (t = -0.263, P > 0.05), IL-10 (t = -0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = -4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = -1.902, P > 0.05), IL-4 (t = -1.333, P > 0.05), IL-10 (t = -1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). CONCLUSIONS: During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

[Research progress in the regulation of pathogenesis and the transformation of chronic liver disease by short-chain fatty acids].

Short-chain fatty acids are metabolites of the intestinal flora and serve as the main energy source for intestinal epithelial cells. At the same time, as important signaling molecules, it regulate a variety of cellular inflammatory responses and homeostatic proliferation through receptor-dependent and independent pathways. Short-chain fatty acids regulate the gut-liver axis and thereby directly act on the liver, participating in the pathogenesis and transformation of various liver diseases, including alcoholic liver disease, metabolic dysfunction-related liver disease, autoimmune liver disease, liver fibrosis, and hepatocellular carcinoma. In addition, short-chain fatty acids can inhibit HBV DNA replication. This article reviews the research progress on the role of short-chain fatty acids in aspects of the pathogenesis and transformation of chronic liver diseases.

[Salivary carcinoma showing thymus-like differentiation: clinicopathological analysis of 7 cases].

Objective: To analyze the clinicopathological features of salivary carcinoma showing thymus-like differentiation(CASTLE). Methods: Cases diagnosed with salivary CASTLE from January 2020 to December 2023 were collected and selected from the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. A total of 7 cases of salivary CASTLE were identified. All the cases originated from parotid. There were 3 males and 4 females. The patients' age range was 11-70 years.The clinical, microscopic, immunohistochemical and prognostic features of these cases were analyzed. Results: The duration of disease ranged from 1 month to 1 year, and 1 patient had facial numbness and 1 with swelling sensation occasionally. Radiographically, 4 cases showed malignant signs. Microscopically, 4 cases involved in parotid gland, and all the tumors had different degrees of lymphoid tissue background. The tumor cells arranged in nests, 5 cases with lymphoepithelial carcinoma-like and 2 cases with squamous cell carcinoma morphology. The tumor cells expressed CD5 and CD117 proteins diffusely in lymphoepithelial carcinoma-like cases. However, the tumor cells expressed CD5 diffusely and CD117 focally in cases with squamous cell carcinoma morphology. All the cases had no Epstein-Barr virus infection. Among the 6 patients with follow-up information, all of them underwent postoperative radiotherapy, and none of them had local recurrence and lymph node metastasis. Conclusions: Salivary CASTLE is a rare tumor, it should be distinguished from lymphoepithelial carcinoma and squamous cell carcinoma. The patients often have better prognosis and CD5 protein expression has a valuable role in the differential diagnosis.

Different microbial ecological agents change the composition of intestinal microbiota and the levels of SCFAs in mice to alleviate loperamide-induced constipation.

Probiotics exert beneficial effects by regulating the intestinal microbiota, metabolism, immune function and other ways of their host. Patients with constipation, a common gastrointestinal disorder, experience disturbances in their intestinal microbiota. In the present study, we investigated the effectiveness of two microbial ecological agents (postbiotic extract PE0401 and a combination of postbiotic extract PE0401 and Lacticaseibacillus paracasei CCFM 2711) in regulating the makeup of the intestinal microbiota and alleviating loperamide hydrochloride-induced constipation in mice. We also preliminarily explored the mechanism underlying their effects. Both microbial ecological agents increased the abundance of the beneficial bacteria Lactobacilli and Bifidobacterium after administration and were able to relieve constipation. However, the degree of improvement in constipation symptoms varied depending on the makeup of the supplement. The postbiotic extract PE0401 increased peristalsis time and improved faecal properties throughout the intestinal tract of the host. PE0401 relieved constipation, possibly by modulating the levels of the constipation-related gastrointestinal regulatory transmitters mouse motilin, mouse vasoactive intestinal peptide, and 5-hydoxytryptamine in the intestinal tract of the host and by increasing the levels of the short-chain fatty acids (SCFAs) acetic acid, propionic acid, and isovaleric acid. It also increased the relative abundance of Lactobacillus and Bifidobacterium and reduced that of Faecalibaculum, Mucispirillum, Staphylococcus, and Lachnoclostridium, which are among the beneficial microbiota in the host intestine. Furthermore, PE0401 decreased the levels of constipation-induced host inflammatory factors. Therefore, the two microbial ecological agents can regulate the intestinal microbiota of constipation mice, and PE0401 has a stronger ability to relieve constipation.

[Application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection in the sphincter-preserving resection of low rectal cancer].

Objectives: To investigate the application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection (LDER) in the anal preservation treatment of low rectal cancer. Methods: Inclusion criteria: (1) age was 18-70; (2) the distance of the lower tumor edge from the anal verge was 4-5 cm; (3) primary tumor with a diameter ≤3 cm; (4) preoperative staging of T1~2N1~2M0; (5) "difficult pelvis", defined as ischial tuberosity diameter<10 cm or body mass index>25 kg/m2; (6) patients with strong intention for sphincter preservation; (7) no preoperative treatment (e.g., chemotherapy, radiotherapy, molecular targeted therapy, or immunotherapy); (8) no lateral lymph node enlargement; (9) no previous anorectal surgery; (10) patients with good basic condition who could tolerate surgery. Exclusion criteria: (1) previously suffered from malignant tumors of the digestive tract or currently suffering from malignant tumors out of the digestive tract; (2) patients with preoperative anal dysfunction (Wexner score ≥ 10), or fecal incontinence. The specific surgical steps are as follows: the distal end of the rectum was dissected to the level of the interspace between internal and external sphincters of anal canal. Five centimeters proximal to the tumor, the mesorectum was ligated, and a liner stapler was used to transect the rectum. The distal rectum with the tumor were then everted and extracted through the anus. The rectum was transected 0.5-1.0 cm distal to the tumor with a linear stapler. Full thickness suture was used to reinforce the stump of the rectum, which was then brought back into the pelvic cavity. Finally, an end-to-end anastomosis between the colon and the rectum was performed. A retrospective descriptive study was performed of the clinical and pathological data of 12 patients with T1-T2 stage low rectal cancer treated with LDER at Henan Provincial People's Hospital from January 2020 to December 2022. Results: All 12 patients successfully completed LDER with sphincter preservation, without conversion to open surgery or changes in surgical approach. The median surgical time was 272 (155-320) minutes, with a median bleeding volume of 100 (50-200) mL. No protective stoma was performed, and all patients received R0 resection. The average hospital stay was 9 (7-15) days. There were no postoperative anastomotic leakage or perioperative deaths. All 12 patients received postoperative follow-up, with a median follow-up of 12 months (6-36 months) and a Wexner score of 8 (5-14) at 6 months postoperatively. There was no tumor recurrence or metastasis during the follow-up period. Conclusions: LDER is safe and effective for the treatment of low rectal cancer.

[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

[New progress in the first-line treatment of advanced hepatocellular carcinoma].

Hepatocellular carcinoma is a kind of cancer with a strong invasion, a high incidence rate and mortality, and a poor prognosis. At the time of diagnosis, most patients are already in the advanced stages of a tumor and have lost the chance for radical surgical treatment. Advanced hepatocellular carcinoma treatment has a gradual transition from systemic chemotherapy to targeted therapy, immunotherapy, and combination therapy, especially immune checkpoint inhibitor-based immunotherapy combination therapy, such as combination with bevacizumab monoclonal antibodies and other drugs, or combination with TACE, HAIC, radiotherapy, ablation, and other treatment methods. Combination therapy has significant synergistic effects and thus has already become a future treatment trend for hepatocellular carcinoma. An immunotherapy-based combination therapy plan will run through the whole process of systemic therapy, which is expected to bring better survival benefits to patients with hepatocellular carcinoma. This article reviews the latest research progress in aspects of the first-line treatment of advanced hepatocellular carcinoma.

Biallelic EPCAM deletions induce tissue-specific DNA repair deficiency and cancer predisposition.

We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss of MSH2. Through the use of patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation of colonic and brain organoids from reprogrammed EPCAMdel iPSC derived from patient fibroblasts. Differentiation of iPSC to epithelial-colonic organoids exhibited continuous increased EPCAM expression and hypermethylation of the MSH2 promoter. This was associated with loss of MSH2 expression, increased mutational burden, MMRD signatures and MS-indel accumulation, the hallmarks of MMRD. In contrast, maturation into brain organoids and examination of blood and fibroblasts failed to show similar processes, preserving MMR proficiency. The combined use of iPSC, organoid technologies and functional genomics analyses highlights the potential of cutting-edge cellular and molecular analysis techniques to define processes controlling tumorigenesis and uncovers a new paradigm of tissue-specific MMRD, which affects the clinical management of these patients.