Objective:To explore the efficacy and safety of combining targeted therapy and immunotherapy with standard chemotherapy in patients with advanced pancreatic cancer.Methods:This is a single-center retrospective cohort study. A total of 123 patients with advanced pancreatic cancer who received first-line systemic treatment at the Second Hospital of Hebei Medical University between January 2022 and December 2024 were retrospectively enrolled. There were 65 males and 58 females,with a mean age of (65.1±10.1) years (range:22 to 88 years). According to whether targeted therapy combined with immunotherapy was added to chemotherapy,patients were divided into a triplet group ( n=46) and a standard chemotherapy group ( n=77). The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included radiological efficacy indicators (objective response rate (ORR), disease control rate (DCR),clinical benefit rate,etc.) and treatment-related adverse events. Propensity score matching (PSM,caliper=0.2) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate survival,and Cox regression models were applied to analyze factors influencing OS and PFS. Results:In the original cohort,the median OS was 11 months in the triplet group and 8 months in the chemotherapy group,with no statistically significant difference ( P=0.056). The median PFS was 5 months in the triplet group and 3 months in the chemotherapy group,also without statistical significance ( P>0.05). Multivariate Cox regression analysis indicated that the triplet regimen was an independent prognostic factor for both OS and PFS ( P<0.05). After PSM,baseline balance between groups was good. The median OS was 10.0 months in the triplet group and 7.0 months in the chemotherapy group, with no significant difference ( P=0.094). In terms of efficacy, the ORR was 26.1% (12/46) in the triplet group versus 7.8% (6/77) in the chemotherapy group,with a statistically significant difference ( χ2=6.320, P=0.012). The DCR was 54.3% (25/46) in the triplet group and 33.8% (26/77) in the chemotherapy group,also statistically significant ( χ2=4.214, P=0.037). The incidence of adverse events was similar between groups,mostly grade 1 to 2. Conclusions:The triplet regimen of chemotherapy,targeted therapy,and immunotherapy shows potential in improving efficacy and prolonging survival with acceptable safety in patients with advanced pancreatic cancer. However, its definitive benefits require further investigation.

Objective:To explore the efficacy and safety of combining targeted therapy and immunotherapy with standard chemotherapy in patients with advanced pancreatic cancer.Methods:This is a single-center retrospective cohort study. A total of 123 patients with advanced pancreatic cancer who received first-line systemic treatment at the Second Hospital of Hebei Medical University between January 2022 and December 2024 were retrospectively enrolled. There were 65 males and 58 females,with a mean age of (65.1±10.1) years (range:22 to 88 years). According to whether targeted therapy combined with immunotherapy was added to chemotherapy,patients were divided into a triplet group ( n=46) and a standard chemotherapy group ( n=77). The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included radiological efficacy indicators (objective response rate (ORR), disease control rate (DCR),clinical benefit rate,etc.) and treatment-related adverse events. Propensity score matching (PSM,caliper=0.2) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate survival,and Cox regression models were applied to analyze factors influencing OS and PFS. Results:In the original cohort,the median OS was 11 months in the triplet group and 8 months in the chemotherapy group,with no statistically significant difference ( P=0.056). The median PFS was 5 months in the triplet group and 3 months in the chemotherapy group,also without statistical significance ( P>0.05). Multivariate Cox regression analysis indicated that the triplet regimen was an independent prognostic factor for both OS and PFS ( P<0.05). After PSM,baseline balance between groups was good. The median OS was 10.0 months in the triplet group and 7.0 months in the chemotherapy group, with no significant difference ( P=0.094). In terms of efficacy, the ORR was 26.1% (12/46) in the triplet group versus 7.8% (6/77) in the chemotherapy group,with a statistically significant difference ( χ2=6.320, P=0.012). The DCR was 54.3% (25/46) in the triplet group and 33.8% (26/77) in the chemotherapy group,also statistically significant ( χ2=4.214, P=0.037). The incidence of adverse events was similar between groups,mostly grade 1 to 2. Conclusions:The triplet regimen of chemotherapy,targeted therapy,and immunotherapy shows potential in improving efficacy and prolonging survival with acceptable safety in patients with advanced pancreatic cancer. However, its definitive benefits require further investigation.

Objective:To explore the association between different feeding methods during the first six months after birth and the physical growth of children aged 3 to 5 years.Methods:Data were from the "Taicang and Wuqiang mother-child cohort study"(TAWS) in China. Children were enrolled at birth between November 2016 and September 2020 and followed up at 1, 2, 3, 6, 8, 12, 18, and 24 months, as well as at ages 3 to 5 years. Based on feeding methods within six months of age, children were categorized into an "exclusive breastfeeding group" and a "formula-feeding group". Birth-related information and feeding practices between 8 and 24 months were collected, alongside dietary habits, physical activity, and illness during preschool years. Height and weight of preschool children were measured to calculate height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), body mass index-for-age Z-score (BAZ), and the rates of stunting, underweight, wasting, overweight, and obesity. After adjusting for demographic factors, birth-related information, feeding practices between 8 to 24 months, preschool dietary habits, physical activity, and health status, multiple linear regression and logistic regression were adopted to analyze the influence of feeding methods within six months of age on the physical growth of children aged 3 to 5 years.Results:A total of 1 233 children were included, comprising 629 boys and 604 girls. The number of children aged 3, 4, and 5 years was 436, 406, and 391, respectively. About 754 children were categorized into the exclusive breastfeeding group and 479 into the formula-feeding group. Children who were introduced to formula milk within six months of age had higher HAZ (0.09±0.99), WAZ (0.24±1.07) and BAZ (0.26±1.11) scores at ages 3 to 5 compared to the exclusive breastfeeding group [HAZ, WAZ, and BAZ were (-0.04±0.92), (0.06±1.02) and (0.11±1.08), respectively]. After adjusting for confounding factors, multiple linear regression analysis showed that the β (95% CI) values for HAZ, WAZ and BAZ in the formula-feeding group were 0.16 (0.06-0.25), 0.17 (0.06-0.29) and 0.15 (0.02-0.27), respectively, compared to the exclusive breastfeeding group. After adjusting for confounding factors, the results of the multivariate logistic regression model indicated that there were no statistically significant differences in the risks of stunting, underweight, wasting, overweight, and obesity during the preschool years between the exclusive breastfeeding group and the formula-feeding group, with OR (95% CI) values of 1.04 (0.41-2.62), 0.99 (0.27-3.57), 1.63 (0.53-4.95), 1.08 (0.66-1.74), and 1.58 (0.70-3.60), respectively. Conclusion:Exclusive breastfeeding within six months of age does not increase the risk of undernutrition (including stunting, underweight or wasting) during preschool years. However, the introduction of formula feeding within six months of age significantly increases the physical growth level of the preschool stage.

Objective:To explore the association between different feeding methods during the first six months after birth and the physical growth of children aged 3 to 5 years.Methods:Data were from the "Taicang and Wuqiang mother-child cohort study"(TAWS) in China. Children were enrolled at birth between November 2016 and September 2020 and followed up at 1, 2, 3, 6, 8, 12, 18, and 24 months, as well as at ages 3 to 5 years. Based on feeding methods within six months of age, children were categorized into an "exclusive breastfeeding group" and a "formula-feeding group". Birth-related information and feeding practices between 8 and 24 months were collected, alongside dietary habits, physical activity, and illness during preschool years. Height and weight of preschool children were measured to calculate height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), body mass index-for-age Z-score (BAZ), and the rates of stunting, underweight, wasting, overweight, and obesity. After adjusting for demographic factors, birth-related information, feeding practices between 8 to 24 months, preschool dietary habits, physical activity, and health status, multiple linear regression and logistic regression were adopted to analyze the influence of feeding methods within six months of age on the physical growth of children aged 3 to 5 years.Results:A total of 1 233 children were included, comprising 629 boys and 604 girls. The number of children aged 3, 4, and 5 years was 436, 406, and 391, respectively. About 754 children were categorized into the exclusive breastfeeding group and 479 into the formula-feeding group. Children who were introduced to formula milk within six months of age had higher HAZ (0.09±0.99), WAZ (0.24±1.07) and BAZ (0.26±1.11) scores at ages 3 to 5 compared to the exclusive breastfeeding group [HAZ, WAZ, and BAZ were (-0.04±0.92), (0.06±1.02) and (0.11±1.08), respectively]. After adjusting for confounding factors, multiple linear regression analysis showed that the β (95% CI) values for HAZ, WAZ and BAZ in the formula-feeding group were 0.16 (0.06-0.25), 0.17 (0.06-0.29) and 0.15 (0.02-0.27), respectively, compared to the exclusive breastfeeding group. After adjusting for confounding factors, the results of the multivariate logistic regression model indicated that there were no statistically significant differences in the risks of stunting, underweight, wasting, overweight, and obesity during the preschool years between the exclusive breastfeeding group and the formula-feeding group, with OR (95% CI) values of 1.04 (0.41-2.62), 0.99 (0.27-3.57), 1.63 (0.53-4.95), 1.08 (0.66-1.74), and 1.58 (0.70-3.60), respectively. Conclusion:Exclusive breastfeeding within six months of age does not increase the risk of undernutrition (including stunting, underweight or wasting) during preschool years. However, the introduction of formula feeding within six months of age significantly increases the physical growth level of the preschool stage.

OBJECTIVES: To investigate the role of mitochondrial autophagy disorder caused by deletion of E3 ubiquitin ligase Parkin in neuroinflammation in a mouse model of MPTP-induced Parkinson's disease (PD). METHODS: Wild-type (WT) male C57BL/6 mice and Parkin^-/- mice were given intraperitoneal injections with MPTP or PBS for 5 consecutive days, and the changes in motor behaviors of the mice were observed using open field test. The effects of Parkin deletion on PD development and neuroinflammation were evaluated using immunofluorescence and Western blotting. The changes of the PINK 1/Parkin signaling pathway in the midbrain substantia nigra of the mice were examined to explore the molecular mechanism of Parkin-mediated regulation of mitochondrial autophagy and its effect on neuroinflammation in PD mice. RESULTS: Compared with their WT counterparts, the Parkin^-/- mice with MPTP injections exhibited significant impairment of motor function with decreased TH⁺ neurons, increased α-synuclein (α-syn) accumulation, and increased numbers of GFAP⁺ and I-ba1⁺ cells in the midbrain substantia nigra. Parkin deletion obviously affected PINK1/Parkin-mediated mitochondrial autophagy to result in significantly increased mtDNA and upregulated expressions of STING and NLRP3 inflammatosomes in the midbrain substantia nigra of MPTP-treated transgenic mice. CONCLUSIONS Parkin deletion causes mitochondrial autophagy disorder to accelerate PD progression and exacerbates neuroinflammation in mice by affecting the PINK1/Parkin signaling pathway, suggesting the important role of Parkin in early pathogenesis of PD.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mice ; Mice, Inbred C57BL ; Male ; Parkinson Disease/genetics* ; Protein Kinases/genetics* ; Mitochondria/metabolism* ; Disease Models, Animal ; Autophagy ; Signal Transduction ; Neuroinflammatory Diseases/metabolism* ; Mice, Knockout ; alpha-Synuclein/metabolism* ; Substantia Nigra/metabolism* ; Mitophagy ; Disease Progression

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

ObjectiveTo mine the medication patterns of Chinese medicines for neurodermatitis based on contemporary medical cases in published articles. MethodThe medical cases of treating neurodermatitis with Chinese medicines were retrieved from the medical case articles published by contemporary famous and old Chinese medicine doctors in the library of Shandong University of Traditional Chinese Medicine， CNKI， VIP， and Wanfang Data. A case library was established， and SPSS Statistics 26.0 and SPSS Modeler 18.0 were employed to analyze the symptoms and syndromes of neurodermatitis and mine the medication patterns. ResultAccording to the inclusion and exclusion criteria， 130 medical case articles were included in this study. Neurodermatitis was prevalent in young adults between 20 and 39 years old （female patients of 30-49 years old and male patients of 20-39 years old）， and male patients were more than female patients. The patients mainly presented the clinical manifestations of itchy rashes， thickened skin， and lichenification. Symptoms included skin injury， emotional abnormalities， and Yin damage caused by prolonged illness. Red tongue， thin white or yellow tongue coating， and wiry pulse were common in the patients. The patients with the syndrome of blood deficiency and wind dryness were often treated with Angelicae Sinensis Radix， Rehmanniae Radix， Glycyrrhizae Radix et Rhizoma， Tribuli Fructus， and Chuanxiong Rhizoma. The commonly used herb pairs included Chuanxiong Rhizoma-Paeoniae Radix Alba， Chuanxiong Rhizoma-Glycyrrhizae Radix et Rhizoma， and Rehmanniae Radix Praeparata-Saposhnikoviae Radix， and the commonly used prescriptions were Siwutang and Dangguiyinzi. The patients with the syndrome of muscle and skin dystrophy were mainly treated with Rehmanniae Radix， Sophorae Flavescentis Radix， Paeoniae Radix Alba， Tribuli Fructus， and Dictamni Cortex. The commonly used herb pairs included Polygoni Multiflori Caulis-Sophorae Flavescentis Radix， Polygoni Multiflori Caulis-Dictamni Cortex， and Salviae Miltiorrhizae Radix et Rhizoma-Paeoniae Radix Alba， and the commonly used prescriptions were Jingjie Siwutang and Baixianpiyin. The patients with the syndrome of liver depression transforming into fire were often treated with Rehmanniae Radix， Gentianae Radix et Rhizoma， Gardeniae Fructus， Bupleuri Radix， and Scutellariae Radix. The commonly used herb pairs included Gentianae Radix et Rhizoma-Polygoni Multiflori Caulis， Polygoni Multiflori Caulis-Gardeniae Fructus， and Gentianae Radix et Rhizoma-Saposhnikoviae Radix， and the commonly used prescriptions were Longdan Xiegantang and Danzhi Xiaoyaosan. ConclusionThis study enriches the knowledge about neurodermatitis， clarifies the treatment principles and methods as well as the medication patterns， and provides a theoretical basis for clinical treatment and medication based on syndrome differentiation.

Objective:To examine the effect of pancreaticojejunostomy with pancreatic duct binding external drainage in laparoscopic pancreatoduodenectomy.Methods:The data of 21 patients who underwent laparoscopic pancreaticoduodenectomy in the same treatment group from January 2017 to October 2019 in Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University were analyzed retrospectively.All patients underwent pancreaticojejunostomy with external drainage of pancreatic ducts.There were 12 males and 9 females, aged (63.1±8.1)years old (range: 46 to 77 years old), body mass index (24.8±3.2)kg/m 2(range: 18.8 to 29.1 kg/m 2).There were 3 cases of hypertension, 5 cases of diabetes, 3 cases of hypertension and diabetes, 3 cases of liver cirrhosis. Results:Laparoscopic pancreatoduodenectomy was successfully performed in all 21 patients.The operation time was (359.3±71.0)minutes, the pancreaticojejunostomy time was (23.8±7.4)minutes, the diameter of pancreatic duct was(3.3±0.6)mm, the intraoperative blood loss was (247.6±90.1)ml, the postoperative hospital stay was(13.7±4.9)days, the leakage of B-level fistula occurred in 1 case(4.8%), and there was no C-level pancreatic fistula.There were 3 cases of bile leakage, 1 case of incision infection, 2 cases of gastroparesis, 1 case of hydrops abdominis, no death and secondary operation.Conclusion:It is a simple and easy method of pancreatoenterostomy with pancreatic duct binding external drainage, which can reduce the incidence of pancreatic fistula and related complications after laparoscopic pancreatoduodenectomy for patients with high risk pancreatic fistula.

Objective:To examine the effect of pancreaticojejunostomy with pancreatic duct binding external drainage in laparoscopic pancreatoduodenectomy.Methods:The data of 21 patients who underwent laparoscopic pancreaticoduodenectomy in the same treatment group from January 2017 to October 2019 in Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University were analyzed retrospectively.All patients underwent pancreaticojejunostomy with external drainage of pancreatic ducts.There were 12 males and 9 females, aged (63.1±8.1)years old (range: 46 to 77 years old), body mass index (24.8±3.2)kg/m 2(range: 18.8 to 29.1 kg/m 2).There were 3 cases of hypertension, 5 cases of diabetes, 3 cases of hypertension and diabetes, 3 cases of liver cirrhosis. Results:Laparoscopic pancreatoduodenectomy was successfully performed in all 21 patients.The operation time was (359.3±71.0)minutes, the pancreaticojejunostomy time was (23.8±7.4)minutes, the diameter of pancreatic duct was(3.3±0.6)mm, the intraoperative blood loss was (247.6±90.1)ml, the postoperative hospital stay was(13.7±4.9)days, the leakage of B-level fistula occurred in 1 case(4.8%), and there was no C-level pancreatic fistula.There were 3 cases of bile leakage, 1 case of incision infection, 2 cases of gastroparesis, 1 case of hydrops abdominis, no death and secondary operation.Conclusion:It is a simple and easy method of pancreatoenterostomy with pancreatic duct binding external drainage, which can reduce the incidence of pancreatic fistula and related complications after laparoscopic pancreatoduodenectomy for patients with high risk pancreatic fistula.

Objective To explore the value of endoscopic retrograde cholangiopancreatography (ERCP) in patients with choledocholithiasis after Billroth Ⅱ gastrointestinal anastomosis.Methods A retrospective cohort study was conducted to retrospective review the data of 189 patients with choledocholithiasis treated by ERCP from December 2015 to November 2017 in Department of Hepatobiliary Surgery,Second Hospital of Hebei Medical University.According to the history of Billroth Ⅱ gastrointestinal anastomosis,the patients who have not undergone digestive surgery were divided into the normal group(n =167) and patients who have undergone digestive surgery were divided into reconstruction group (n =22).The operation time,the success rate of stone extraction,complications,the hospitalization time,total hospitalization expenses were compared between the two groups.Measurement data with normal distribution were represented as (Mean ± SD) and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range).Comparisons of count data were analyzed using the x2 test or Fisher exact probability.Results The operation time of the normal group was (40.18 ± 11.80) min,and the success rate of ERCP was 97.60％ (163/167),the operation time of reconstruction group was(61.81 ± 13.21) min,and the success rate of ERCP was 81.82％ (18/22),There were significant differences between the two groups (t =0.105,x2 =10.400,P ＜ 0.05).The complications,the hospitalization time and the total hospitalization expense of the normal group were 16.17％ (27/167),(3.47 ± 1.55) d,(20 620.69 ± 3 117.88) yuan,the reconstruction group were 18.18％ (4/22),(4.18 ± 2.08) d,(22 426.41 ±5 916.30) yuan,with no statistically significant difference (x2 =0.000,t =4.204),t =10.828,P ＞ 0.05).Conclusions ERCP is safe and feasible for patients with choledocholithiasis after Billroth Ⅱ gastrointestinal anastomosis.It also has a high success rate of stone removal and small trauma,which is worthy of promotion.