Objective:To explore the efficacy and safety of orelabrutinib combined with R-CHOP in patients with high-risk nongerminal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL) with extranodal involvement.Methods:This retrospective study was conducted on 35 patients who were seen at Guangxi Medical University Cancer Hospital and were immunohistochemically confirmed to have non-GCB DLBCL, had an International Prognostic Index score of 3 - 5, and confirmed to have ≥2 extranodal involvement on PET/CT. The treatment comprised the standard R-CHOP regimen combined with oral orelabrutinib (150 mg/day) for six cycles. In patients who developed neutropenia or grade 3 neutropenia with fever during treatment, administration of prophylactic pegylated granulocyte colony-stimulating factor 48 h after the end of chemotherapy was started on the next cycle. The endpoints included overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS) time, overall survival (OS) time, and safety assessment.Results:The 35 eligible patients enrolled had a median age of 53 years (21 - 72 years) and a median follow-up time of 28 months (12 - 36 months) ; 19 patients had double-expressor (DE) status. The ORR was 88.6%, and the CR rate was 68.6%. The 2-year PFS and OS rates were 68.6% (95% CI 54.0% - 7.2%) and 87.5% (95% CI 76.7% - 100%), respectively. The 2-year PFS rate was significantly lower in patients with DE status than in those without DE status [54.4% (95% CI 35.4% - 84.2%) vs. 85.2% (95% CI 68.3% - 100%), P=0.048]. Serious adverse events included febrile neutropenia, pneumonia, and atrial flutter, but no treatment-related deaths. Conclusion:In patients with high-risk non-GCB DLBCL and extranodal involvement, the combination of orelabrutinib with R-CHOP regimen had good efficacy and manageable toxicity.

Objective:To investigate the clinical efficacy of radical gastrectomy with mesan-gientization via the inferior margin of the pancreas approach (GMIP).Methods:The retrospective cohort study was conducted. The clinicopathological data of 255 patients of Siewert Ⅱ and (or) Ⅲ adenocarcinoma of esophagogastric junction (AEG) who were admitted to Cancer Hospital Affiliated to Shanxi Medical University from March 2024 to March 2025 were collected. There were 191 males and 64 females, aged (62 ±7)years. Of 255 patients, 152 cases undergoing GMIP were allocated into the mesangientization radical resection group, 103 cases undergoing D 2 radical resection of gastric cancer were allocated into D 2 radical resection group. Observation indicators: (1) surgical and post-operative situations; (2) lymph node dissection status. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Wilcoxon test. Comparison of count data between groups was conducted using the chi-square test or corrected chi-square test. Compari-son of ordinal data was conducted using the rank sum test. Results:(1) Surgical and postoperative situations. In the mesangientization radical resection group, the time of lymph node dissection was (115±14)minutes, volume of intraoperative blood loss was (81±37)mL. In the D 2 radical resection group, the above indicators were (97±13)minutes, (104±39)mL, respectively. There were significant differences in the above indicators between the two groups ( t=-8.68, -4.64, P<0.05). In the mesan-gientization radical resection group, the total number of examined lymph node was 40.00(10.00), the number of lymph node dissected (the total number of each group) was 29.00(5.00), the number of lymph node metastasis (the total number of each group) was 2.00(1.00). In the D 2 radical resection group, the above indicators were 27.00(9.00), 8.00(4.00), 1.00(1.00), respec-tively. There were significant differences in the above indicators between the two groups ( Z=-10.68, -13.57, -6.80, P<0.05). (3) Lymph node dissection status. There were significant differences in number of lymph node dissected of No.14v, 12a, 12p, 11d, 11p, 10, postgastric, 9, 8a, 8p lymph node between the mesangientization radical resection group and the D 2 radical resection group ( P<0.05). There were significant differences in number of lymph node metastasis of No.11d and postgastric lymph node between the mesangientization radical resection group and the D 2 radical resection group ( P<0.05). Conclusion:Compared with D 2 radical resection, the GMIP for Siewert Ⅱ or Ⅲ AEG has less volume of intraoperative blood loss and more complete lymph node dissection.

Objective:To summarize the clinicopathological features, evolving trends in treatment and surgical approaches, and survival outcomes of patients who underwent D2 radical gastrectomy for gastric cancer in Shanxi Provincial Cancer Hospital over the past 11 years with the goal of providing a reference for the clinical practice of gastric cancer in this region.Methods:A retrospective observational study was conducted to analyze the clinicopathological data of patients who underwent D2 radical gastrectomy for pathologically confirmed gastric malignancy at the Department of Gastrointestinal Surgery, Shanxi Provincial Cancer Hospital from January, 2013 to December, 2023. Exclusion criteria consisted of: (1) residual gastric cancer or recurrent gastric cancer after surgery; (2) emergency gastric cancer resection due to bleeding, perforation, obstruction, or other causes; (3) comorbidity with other primary malignant tumors; (4) severe preoperative cardiopulmonary insufficiency or hepatic and renal insufficiency who cannot tolerate radical surgery; and (5) inconsistent main diagnosis information across the medical record system, pathological system, and gastric cancer-specific database. Patients were divided into three groups based on treatment methods: the surgery-only group, the perioperative chemotherapy group, and the adjuvant chemotherapy group. Endpoints included: (1) baseline patient characteristics; (2) trends in tumor location and pathological features; (3) evolution of treatment modalities; and (4) survival outcomes.Results:A total of 15,644 patients were included in the analysis, with 12,591 males and 3,053 females, the male-to-female gender ration was approximately 4∶1; the mean age was (61.2±9.5) years. The tumor sites were mainly concentrated in the esophagogastric junction (EGJ) (57.4%), followed by the antrum (25.9%). The incidence of EGJ cancer initially rose and then declined. However, gastric antrum tumors remained stable, and gastric body tumors showed a slow upward trend after 2020, accounting for 16.7%. In terms of pathological types, poorly differentiated carcinoma was the most prevalent, accounting for 55.9%, followed by moderately differentiated carcinoma (24.2%), mucinous adenocarcinoma (or signet ring cell carcinoma,14.1%), neuroendocrine carcinoma (4.8%), and well-differentiated carcinoma (0.9%). The proportion of poorly differentiated adenocarcinoma showed a significant upward trend overall as well, peaking at 65.6% in 2022 and decreasing to 57.5% in 2023. Mucinous adenocarcinoma (or signet ring cell carcinoma) exhibited fluctuations with a first increase followed by a decrease: it peaked at 17.3% in 2018, dropped sharply to 8.4% in 2022, and rose back to 13.8% in 2023. The proportions of well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, and neuroendocrine tumors remained stable year by year. In terms of pathological staging, the overall proportions of gastric cancer at Stage 0, Stage I, Stage II, Stage III, and Stage IVa were 0.5%, 17.3%, 25.1%, 54.9%, and 2.3%, respectively. For Stage III, its proportion was 74.6% in 2013, which decreased to 46.4% by 2023. Stages I and II gastric cancer showed an upward trend, with their proportions rising from 10.2% and 12.1% in 2013 to nearly 21.0% and 29.6% in 2023, respectively. Between 2013 and 2023, the proportion of patients who received surgery alone continued to decrease, with this proportion dropping to 34.7% in 2023. In contrast, the number of patients who received adjuvant chemotherapy increased year by year, reaching 54.2% in 2023. Since 2017, the application of perioperative chemotherapy has gradually increased, rising to 11.1% in 2023. Immunotherapy showed an almost synchronous growth trend with perioperative chemotherapy. However, targeted therapy exhibited a downward trend after a period of growth. There were 10,704 cases of open surgery (68.4%), 4,744 cases of laparoscopic surgery (30.3%), and 193 cases of transthoracic surgery (1.2%). Pathological margin positivity was observed in 443 cases (2.8%), and the volume of gastric cancer surgeries gradually increased, peaked in 2021 before subsequently decreasing gradually. However, the volume of laparoscopic surgeries did not decrease; instead, it showed an upward trend. The main resection method for EGJ tumors was total gastrectomy, accounting for 78.5% of the total, followed by proximal gastrectomy, which accounted for 21.5%. After total gastrectomy, esophagojejunal Roux-en-Y anastomosis was the primary anastomotic method, and for proximal gastrectomy, the main anastomotic method was esophagogastric anastomosis, which accounted for 68.0% of the total. For distal gastrectomy, Billroth II anastomosis was the most common anastomotic technique, accounting for 92.7% of these procedures. The overall incidence of postoperative complications was 14.5% (2,264/15,644), among which the incidence of severe complications (grades III-IV) was 4.5% (706/15,644). The entire cohort was followed up with for (47.1±36.8) months, and the 1-year, 3-year, and 5-year overall survival rates were 86.4%, 65.9%, and 58.1%, respectively. For patients with stage 0, I, II, III, and IV gastric adenocarcinoma, the 1-year overall survival rates were 95.7%, 98.0%, 89.4%, 81.0%, and 49.1%, respectively; the 3-year overall survival rates were 92.1%, 94.6%, 81.9%, 51.4%, and 14.7%, respectively; and the 5-year overall survival rates were 89.4%, 91.7%, 75.1%, 41.5%, and 10.0%, respectively. For patients with stage I, II, III, and IV gastric neuroendocrine carcinoma, the 1-year overall survival rates were 96.7%, 91.1%, 73.8%, and 52.6%, respectively; the 3-year overall survival rates were 87.2%, 69.6%, 46.1%, and 32.1%, respectively; and the 5-year overall survival rates were 87.2%, 62.2%, 36.7%, and 32.1%, respectively.Conclusions:Gastric cancer in Shanxi Province is characterized by a male predominance, a high prevalence of tumors at the esophagogastric junction, a large proportion of poorly differentiated adenocarcinoma, and presentation at advanced stages (predominantly Stage III). The detection rate of early gastric cancer has been increasing year by year, the volume of laparoscopic surgeries has been on the rise annually, and the treatment model has shifted from single surgery to comprehensive treatment.

Objective:To explore the efficacy and safety of orelabrutinib combined with R-CHOP in patients with high-risk nongerminal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL) with extranodal involvement.Methods:This retrospective study was conducted on 35 patients who were seen at Guangxi Medical University Cancer Hospital and were immunohistochemically confirmed to have non-GCB DLBCL, had an International Prognostic Index score of 3 - 5, and confirmed to have ≥2 extranodal involvement on PET/CT. The treatment comprised the standard R-CHOP regimen combined with oral orelabrutinib (150 mg/day) for six cycles. In patients who developed neutropenia or grade 3 neutropenia with fever during treatment, administration of prophylactic pegylated granulocyte colony-stimulating factor 48 h after the end of chemotherapy was started on the next cycle. The endpoints included overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS) time, overall survival (OS) time, and safety assessment.Results:The 35 eligible patients enrolled had a median age of 53 years (21 - 72 years) and a median follow-up time of 28 months (12 - 36 months) ; 19 patients had double-expressor (DE) status. The ORR was 88.6%, and the CR rate was 68.6%. The 2-year PFS and OS rates were 68.6% (95% CI 54.0% - 7.2%) and 87.5% (95% CI 76.7% - 100%), respectively. The 2-year PFS rate was significantly lower in patients with DE status than in those without DE status [54.4% (95% CI 35.4% - 84.2%) vs. 85.2% (95% CI 68.3% - 100%), P=0.048]. Serious adverse events included febrile neutropenia, pneumonia, and atrial flutter, but no treatment-related deaths. Conclusion:In patients with high-risk non-GCB DLBCL and extranodal involvement, the combination of orelabrutinib with R-CHOP regimen had good efficacy and manageable toxicity.

Objective:To investigate the clinical efficacy of radical gastrectomy with mesan-gientization via the inferior margin of the pancreas approach (GMIP).Methods:The retrospective cohort study was conducted. The clinicopathological data of 255 patients of Siewert Ⅱ and (or) Ⅲ adenocarcinoma of esophagogastric junction (AEG) who were admitted to Cancer Hospital Affiliated to Shanxi Medical University from March 2024 to March 2025 were collected. There were 191 males and 64 females, aged (62 ±7)years. Of 255 patients, 152 cases undergoing GMIP were allocated into the mesangientization radical resection group, 103 cases undergoing D 2 radical resection of gastric cancer were allocated into D 2 radical resection group. Observation indicators: (1) surgical and post-operative situations; (2) lymph node dissection status. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Wilcoxon test. Comparison of count data between groups was conducted using the chi-square test or corrected chi-square test. Compari-son of ordinal data was conducted using the rank sum test. Results:(1) Surgical and postoperative situations. In the mesangientization radical resection group, the time of lymph node dissection was (115±14)minutes, volume of intraoperative blood loss was (81±37)mL. In the D 2 radical resection group, the above indicators were (97±13)minutes, (104±39)mL, respectively. There were significant differences in the above indicators between the two groups ( t=-8.68, -4.64, P<0.05). In the mesan-gientization radical resection group, the total number of examined lymph node was 40.00(10.00), the number of lymph node dissected (the total number of each group) was 29.00(5.00), the number of lymph node metastasis (the total number of each group) was 2.00(1.00). In the D 2 radical resection group, the above indicators were 27.00(9.00), 8.00(4.00), 1.00(1.00), respec-tively. There were significant differences in the above indicators between the two groups ( Z=-10.68, -13.57, -6.80, P<0.05). (3) Lymph node dissection status. There were significant differences in number of lymph node dissected of No.14v, 12a, 12p, 11d, 11p, 10, postgastric, 9, 8a, 8p lymph node between the mesangientization radical resection group and the D 2 radical resection group ( P<0.05). There were significant differences in number of lymph node metastasis of No.11d and postgastric lymph node between the mesangientization radical resection group and the D 2 radical resection group ( P<0.05). Conclusion:Compared with D 2 radical resection, the GMIP for Siewert Ⅱ or Ⅲ AEG has less volume of intraoperative blood loss and more complete lymph node dissection.

Objective:To summarize the clinicopathological features, evolving trends in treatment and surgical approaches, and survival outcomes of patients who underwent D2 radical gastrectomy for gastric cancer in Shanxi Provincial Cancer Hospital over the past 11 years with the goal of providing a reference for the clinical practice of gastric cancer in this region.Methods:A retrospective observational study was conducted to analyze the clinicopathological data of patients who underwent D2 radical gastrectomy for pathologically confirmed gastric malignancy at the Department of Gastrointestinal Surgery, Shanxi Provincial Cancer Hospital from January, 2013 to December, 2023. Exclusion criteria consisted of: (1) residual gastric cancer or recurrent gastric cancer after surgery; (2) emergency gastric cancer resection due to bleeding, perforation, obstruction, or other causes; (3) comorbidity with other primary malignant tumors; (4) severe preoperative cardiopulmonary insufficiency or hepatic and renal insufficiency who cannot tolerate radical surgery; and (5) inconsistent main diagnosis information across the medical record system, pathological system, and gastric cancer-specific database. Patients were divided into three groups based on treatment methods: the surgery-only group, the perioperative chemotherapy group, and the adjuvant chemotherapy group. Endpoints included: (1) baseline patient characteristics; (2) trends in tumor location and pathological features; (3) evolution of treatment modalities; and (4) survival outcomes.Results:A total of 15,644 patients were included in the analysis, with 12,591 males and 3,053 females, the male-to-female gender ration was approximately 4∶1; the mean age was (61.2±9.5) years. The tumor sites were mainly concentrated in the esophagogastric junction (EGJ) (57.4%), followed by the antrum (25.9%). The incidence of EGJ cancer initially rose and then declined. However, gastric antrum tumors remained stable, and gastric body tumors showed a slow upward trend after 2020, accounting for 16.7%. In terms of pathological types, poorly differentiated carcinoma was the most prevalent, accounting for 55.9%, followed by moderately differentiated carcinoma (24.2%), mucinous adenocarcinoma (or signet ring cell carcinoma,14.1%), neuroendocrine carcinoma (4.8%), and well-differentiated carcinoma (0.9%). The proportion of poorly differentiated adenocarcinoma showed a significant upward trend overall as well, peaking at 65.6% in 2022 and decreasing to 57.5% in 2023. Mucinous adenocarcinoma (or signet ring cell carcinoma) exhibited fluctuations with a first increase followed by a decrease: it peaked at 17.3% in 2018, dropped sharply to 8.4% in 2022, and rose back to 13.8% in 2023. The proportions of well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, and neuroendocrine tumors remained stable year by year. In terms of pathological staging, the overall proportions of gastric cancer at Stage 0, Stage I, Stage II, Stage III, and Stage IVa were 0.5%, 17.3%, 25.1%, 54.9%, and 2.3%, respectively. For Stage III, its proportion was 74.6% in 2013, which decreased to 46.4% by 2023. Stages I and II gastric cancer showed an upward trend, with their proportions rising from 10.2% and 12.1% in 2013 to nearly 21.0% and 29.6% in 2023, respectively. Between 2013 and 2023, the proportion of patients who received surgery alone continued to decrease, with this proportion dropping to 34.7% in 2023. In contrast, the number of patients who received adjuvant chemotherapy increased year by year, reaching 54.2% in 2023. Since 2017, the application of perioperative chemotherapy has gradually increased, rising to 11.1% in 2023. Immunotherapy showed an almost synchronous growth trend with perioperative chemotherapy. However, targeted therapy exhibited a downward trend after a period of growth. There were 10,704 cases of open surgery (68.4%), 4,744 cases of laparoscopic surgery (30.3%), and 193 cases of transthoracic surgery (1.2%). Pathological margin positivity was observed in 443 cases (2.8%), and the volume of gastric cancer surgeries gradually increased, peaked in 2021 before subsequently decreasing gradually. However, the volume of laparoscopic surgeries did not decrease; instead, it showed an upward trend. The main resection method for EGJ tumors was total gastrectomy, accounting for 78.5% of the total, followed by proximal gastrectomy, which accounted for 21.5%. After total gastrectomy, esophagojejunal Roux-en-Y anastomosis was the primary anastomotic method, and for proximal gastrectomy, the main anastomotic method was esophagogastric anastomosis, which accounted for 68.0% of the total. For distal gastrectomy, Billroth II anastomosis was the most common anastomotic technique, accounting for 92.7% of these procedures. The overall incidence of postoperative complications was 14.5% (2,264/15,644), among which the incidence of severe complications (grades III-IV) was 4.5% (706/15,644). The entire cohort was followed up with for (47.1±36.8) months, and the 1-year, 3-year, and 5-year overall survival rates were 86.4%, 65.9%, and 58.1%, respectively. For patients with stage 0, I, II, III, and IV gastric adenocarcinoma, the 1-year overall survival rates were 95.7%, 98.0%, 89.4%, 81.0%, and 49.1%, respectively; the 3-year overall survival rates were 92.1%, 94.6%, 81.9%, 51.4%, and 14.7%, respectively; and the 5-year overall survival rates were 89.4%, 91.7%, 75.1%, 41.5%, and 10.0%, respectively. For patients with stage I, II, III, and IV gastric neuroendocrine carcinoma, the 1-year overall survival rates were 96.7%, 91.1%, 73.8%, and 52.6%, respectively; the 3-year overall survival rates were 87.2%, 69.6%, 46.1%, and 32.1%, respectively; and the 5-year overall survival rates were 87.2%, 62.2%, 36.7%, and 32.1%, respectively.Conclusions:Gastric cancer in Shanxi Province is characterized by a male predominance, a high prevalence of tumors at the esophagogastric junction, a large proportion of poorly differentiated adenocarcinoma, and presentation at advanced stages (predominantly Stage III). The detection rate of early gastric cancer has been increasing year by year, the volume of laparoscopic surgeries has been on the rise annually, and the treatment model has shifted from single surgery to comprehensive treatment.

Background Currently,the diagnosis of depressive disorder relies on symptomatology,which is greatly influenced by subjective factors such as clinicians' experience.Finding more accurate and reliable quantitative diagnostic methods is currently an urgent problem.Objective To explore the value of Fisher discriminant function based on inflammatory cytokines in the diagnosis of depressive disorder,so as to provide references for clinical diagnosis.Methods A total of 136 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)criteria,who underwent inpatient treatment at Hebei Mental Health Center from April 2020 to November 2020,were enrolled as study group.67 healthy participants matched for age and gender,was recruited during the same period.Serum levels of inflammatory cytokine were measured using enzyme-linked immunosorbent assay(ELISA).Fisher discriminant model was employed to establish a discriminant function for inflammatory cytokines exhibiting significant statistical differences between study group and control group,which was then validated.Results The levels of pro-inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6),interferon-γ(INF-γ)and tumor necrosis factor-α(TNF-α)were higher in the study group compared with control group,with statistically significant differences(U=9.115,5.239,4.431,5.428,P<0.01).Conversely,the levels of anti-inflammatory cytokines interleukin-4(IL-4),interleukin-10(IL-10)and interleukin-13(IL-13)were lower in the study group compared with control group,with statistically significant differences(U=7.398,7.331,7.614,P<0.01).The retrospective test in Fisher discriminant function achieved a correct discrimination rate of 89.66%,and the cross validation achieved a correct discrimination rate of 88.67%.Conclusion The Fisher discriminant function developed in this study may serve as a valuable auxiliary method in the diagnosis of depressive disorder.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

The clinical data of a case of Niemann-Pick disease type C diagnosed at Beijing Children′s Hospital, Capital Medical University on December 22, 2017 were retrospectively analyzed.The patient, male, 1 year and 28 days old, was admitted to the hospital primarily due to intermittent fever, cough and dyspnea for 8 months, and hepatosplenomegaly for 20 days.The patient initially presented with cough, expectoration, and wheezing, followed by hypotonia and delayed motor development.At the age of 1 year, the child developed hepatosplenomegaly and diffuse interstitial changes in both lungs.At the age of 3 years, the child had obvious vertical supranuclear gaze palsy and gelastic cataplexy, followed by dysarthria and dysphagia.The foam cells were found by bone marrow cytology, while sphingomyelinase and glucocerebrosidase were normal, so Niemann-Pick disease type A/B and Gaucher disease were excluded.Finally, genetic testing revealed two pathogenic mutations in the NPC1 gene, so Niemann-Pick disease type C was confirmed.Miglustat treatment began when the child was 3 years old, and vertical supranuclear gaze palsy and gelastic cataplexy improved for a while, but then the neurological symptoms worsened again, with dysphagia and dyspnea gradually increasing, and finally he died at the age of 4 years and 11 months.

Objective To establish a liver-specific Rbp4 gene knockout mouse model and to explore the effect of liver Rbp4 gene deletion on glucose metabolism.Methods Cre-LoxP technology was used to construct a liver-specific Rbp4 gene knockout mouse model using C57/BL6J and Alb-Cre mice.The genotype of the mice was identified by polymerase chain reaction and agarose gel electrophoresis.Ten 18 week old C57/BL6J male mice were included in the WT group,10 flox homozygous and Alb-Cre negative mice of the same age were included in the experimental control group(Rbp4flox/flox:Cre-),and 10 flox homozygous and Alb-Cre positive mice of the same age were included in the experimental group(Rbp4flox/flox:Cre+).Expression levels of RBP4 protein and mRNA in the liver were verified by Western Blot and quantitative reverse transcription-polymerase chain reaction(qRT-PCR),respectively,and expression levels of Rbp4 mRNA in other tissues were detected by qRT-PCR.Morphological changes in liver tissue were detected by hematoxylin and eosin staining.Blood glucose values were detected in mouse tail vein blood samples using a blood glucose meter,and glucose tolerance and insulin tolerance were determined.Expression levels of the liver glucose metabolism genes phosphoenolpyruvate carboxylase(Pepck)and glucose-6-phosphatase(G6pase)were detected by qRT-PCR.Results Liver-specific Rbp4 knockout mice were successfully bred and identified.RBP4 protein and mRNA levels were significantly decreased in the liver of Rbp4flox/flox:Cre+mice(P＜0.05),but there was no significant difference in the relative expression levels of Rbp4 mRNA in fat,kidney,pancreas,spleen,heart,or muscle tissues among the three groups(P＞0.05).Liver-specific Rbp4 knockout had no significant effect on liver morphology,glucose tolerance,or insulin tolerance(P＞0.05).Pepck mRNA levels in the liver differed significantly among the three groups(P＜0.05),and pairwise comparison showed that liver Pepck mRNA levels were significantly lower in Rbp4flox/flox:Cre+mice compared with levels in Rbp4flox/flox:Cre-mice(P＜0.05).There was no significant difference in liver glucose-6-phosphatase(G6pase)mRNA expression among the three groups(P＞0.05).Conclusions We successfully constructed a liver-specific Rbp4 knockout mouse model.Deletion of Rbp4 in the liver inhibited expression of Pepck mRNA in the liver,thus providing a basis for further exploration of the role of this gene in glucose metabolism in mice.