This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To evaluate the role of stimulator of interferon genes (STING) in postoperative cognitive dysfunction (POCD) and the relationship with pyroptosis in hippocampal cells in aged mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 18 months, weighing 23-28 g, were assigned to 4 groups ( n=12 each) using a random number table method: control group (C group), POCD group (P group), STING inhibitor C-176 group (PC group), and C-176 solvent group (PV group). The mice underwent Morris water maze training for 4 days prior to model establishment. Mice in P, PC and PV groups underwent tibial fracture and intramedullary pin fixation under sevoflurane anesthesia to establish the POCD model, while mice in C group received no treatment. The STING inhibitor C-176 (750 nmol/200 μl) and an equal volume of C-176 solvent were intraperitoneally injected at 30 min before establishment of the model in PC and PV groups, respectively. The open field test was performed on the 5th day after model preparation, the novel object recognition test was conducted on the 6th day, and the Morris water maze test was performed on the 7th day. Mice were sacrificed under anesthesia to collect the hippocampus for determination of the expression of STING, phosphorylated STING (p-STING), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cleaved caspase-1, and gasdermin-D (GSDMD)-NT by Western blot. Results:There were no statistically significant differences in the parameters of the training phase of the Morris water maze test and the open field test among the four groups ( P>0.05). Compared with C group, the recognition index in the novel object recognition test was significantly decreased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was shortened in the Morris water maze test, and the expression of STING, NLRP3, cleaved caspase-1, and GSDMD-NT in hippocampal neurons was up-regulated in P, PC and PV groups, and the expression of p-STING was significantly up-regulated in P and PV groups ( P<0.05). Compared with P group, the recognition index in the novel object recognition test was significantly increased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was prolonged in the Morris water maze test, and the expression of p-STING, NLRP3, cleaved caspase-1, and GSDMD-NT in hippocampal neurons was down-regulated in PC group ( P<0.05). Compared with PC group, the recognition index in the novel object recognition test was significantly decreased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was shortened in the Morris water maze test, and the expression of p-STING, NLRP3, cleaved caspase-1 and GSDMD-NT was up-regulated in PV group ( P<0.05). Conclusions:STING is involved in the development of POCD in aged mice, and the mechanism may be related to promotion of pyroptosis in hippocampal cells.

Objective To systematically evaluate and analyze qualitative studies of parental engagement in kangaroo mother care experiences for preterm infants in the NICU,aiming to provide references for promoting the early recovery of preterm infants in NICU and improving the quality of nursing services.Methods Relevant were searched for qualitative studies of parental engagement in kangaroo mother care for preterm infants in NICU.The search time limit was from the construction of the database to July 19,2024.The quality of the included literature was assessed using the Joanna Brigg Institute's(JBI)Australian Centre for Evidence-Based Health Care's Quality Assessment Criteria for Qualitative Research,and the results were integrated using the meta-integration methods.Results A total of 17 papers were included in the literature,and 61 findings were extracted,grouped into 10 new categories.These were further synthesized into 4 integrated findings:physical and psychological perceptions of participation in kangaroo mother care;challenges to participation in kangaroo mother care;facilitators of participation in kangaroo mother care;expectations and suggestions for kangaroo mother care.Conclusion Hospital administrators should further improve the management specifications of kangaroo mother care for preterm infants in NICU,optimize resource allocation and strengthen publicity.At the same time,healthcare professionals should actively promote the establishment of peer and family support systems and increase participation in kangaroo mother care to facilitate early recovery of preterm infants in NICU and to continuously promote the improvement of nursing service quality.

Objective To characterize the clinical features of the group of gout patients to facilitate earlier identifi-cation,and optimize the diagnosis and treatment of the condition.Methods The retrospective study analyzed 24 gout patients with shoulder joint(s)involved and consulted by physicians of Peking Union Medical College Hospital from March 2021 to April 2025,while 70 outpatient gout patients matched by clinical course duration and sex were enrolled as control group.Clinical data including medical history,laboratory tests,therapeutic interventions.Prog-nosis was systematically collected to delineate the distinctive clinical manifestations of the patients.Results All 24 gout patients with shoulder joints involved were male,aged(43.16±13.13)years and had an average BMI of 27.70±4.63.The duration of gout was 8(5,12)years while of those patients had an early onset before 30 years old.The maximal serum uric acid concentration was(754.15±175.79)μmol/L.It was shown by case review that 16.67％of the patients were asymptomatic,and 79.17％suffered from shoulder pain.A quarter of the patients developed subcutaneous tophi.All the patients affected(P＜0.05).The affected joints ascended from lower extremities to the upper averagely took 4.72±2.80 years and had heavier burden of hyperuricemia(P＜0.05),while no significant difference was found in renal function and inflammation level.Conclusions Gout patients with shoulder joints involvement are older and have atypical manifestation.The diagnosis needs support of imaging or ar-throcentesis.

Objective:To evaluate the alveolar ridge preservation effect of immediate implantation at extraction site with the im-proved CBCT measuring method.Methods:Eighty patients with extraction site were divided into test group A,B,C and control group.The patients were treated by means of immediate implant placement combined with large flap surgery,guided bone regener-ation(GBR)using mass Bio-Oss bone particles in the group A(the thickness of facial bone wall＜1 mm);The patients were trea-ted by means of immediate implant placement combined without flap surgery and bone graft in the group B(the thickness of facial bone wall ≥1 mm and＜2 mm)and C(the thickness of facial bone wall ≥2 mm),the CGF was implanted in the jumping space only when the thickness of jumping space was＞2 mm.In the control group,the alveolar sockets healed naturally without any in-tervention or treatment.CBCT was taken before surgery,immediately after surgery,and 6 months after surgery to evaluate the height and width of alveolar bone,the thickness of facial bone wall and jumping space.Results:The reduction of alveolar ridge height in group A,B,C and control group was(0.41±0.13,0.94±0.18,0.59±0.12,1.31±0.19)mm,The reduction of alveolar ridge width in group A,B,C and control group was(0.93±0.10,1.48±0.21,1.12±0.17,1.66±0.16)mum.The re-sults of four groups were statistically different(F=177.0,P＜0.001;F=125.3,P＜0.001).The alveolar ridge thickness of facial bone wall in group A,B,C and con-trol group was(0.98±0.25,2.39±0.28)mm,(1.43±0.52,2.10±0.33)mm,(2.17±0.41,2.79±0.27)mm before surgery and six months after immediate implantation.The results of each group were statistically different between before surgery and six months after immediate implantation(t=16.45,P＜0.001;t=7.357,P＜0.001;t=5.488,P＜0.001).Patients in three test groups had the thickness of jumping space＞2 mm and ≤2 mm,and the reduction of alveolar ridge width was(0.78±0.18,0.88±0.17)mm.The results were statistically different(t=17.18,P=0.018).Conclusion:The alveolar ridge preservation was obtained by means of immediate implant placement combined with large flap surgery,guided bone regeneration(GBR)using mass Bio-Oss bone particles at extraction site with the thickness of facial bone wall＜1 mm;The alveolar ridge preservation was obtained without flap surgery and GBR at extraction site with the thickness of facial bone wall≥1 mm.The preservation of soft and hard tissue was better in the axial palatal side of immediate implantation with the thickness of jumping space＞2 mm than that with the thickness of jumping space≤2 mm.

Objective:To evaluate the role of stimulator of interferon genes (STING) in postoperative cognitive dysfunction (POCD) and the relationship with pyroptosis in hippocampal cells in aged mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 18 months, weighing 23-28 g, were assigned to 4 groups ( n=12 each) using a random number table method: control group (C group), POCD group (P group), STING inhibitor C-176 group (PC group), and C-176 solvent group (PV group). The mice underwent Morris water maze training for 4 days prior to model establishment. Mice in P, PC and PV groups underwent tibial fracture and intramedullary pin fixation under sevoflurane anesthesia to establish the POCD model, while mice in C group received no treatment. The STING inhibitor C-176 (750 nmol/200 μl) and an equal volume of C-176 solvent were intraperitoneally injected at 30 min before establishment of the model in PC and PV groups, respectively. The open field test was performed on the 5th day after model preparation, the novel object recognition test was conducted on the 6th day, and the Morris water maze test was performed on the 7th day. Mice were sacrificed under anesthesia to collect the hippocampus for determination of the expression of STING, phosphorylated STING (p-STING), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cleaved caspase-1, and gasdermin-D (GSDMD)-NT by Western blot. Results:There were no statistically significant differences in the parameters of the training phase of the Morris water maze test and the open field test among the four groups ( P>0.05). Compared with C group, the recognition index in the novel object recognition test was significantly decreased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was shortened in the Morris water maze test, and the expression of STING, NLRP3, cleaved caspase-1, and GSDMD-NT in hippocampal neurons was up-regulated in P, PC and PV groups, and the expression of p-STING was significantly up-regulated in P and PV groups ( P<0.05). Compared with P group, the recognition index in the novel object recognition test was significantly increased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was prolonged in the Morris water maze test, and the expression of p-STING, NLRP3, cleaved caspase-1, and GSDMD-NT in hippocampal neurons was down-regulated in PC group ( P<0.05). Compared with PC group, the recognition index in the novel object recognition test was significantly decreased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was shortened in the Morris water maze test, and the expression of p-STING, NLRP3, cleaved caspase-1 and GSDMD-NT was up-regulated in PV group ( P<0.05). Conclusions:STING is involved in the development of POCD in aged mice, and the mechanism may be related to promotion of pyroptosis in hippocampal cells.

Objective To systematically evaluate and analyze qualitative studies of parental engagement in kangaroo mother care experiences for preterm infants in the NICU,aiming to provide references for promoting the early recovery of preterm infants in NICU and improving the quality of nursing services.Methods Relevant were searched for qualitative studies of parental engagement in kangaroo mother care for preterm infants in NICU.The search time limit was from the construction of the database to July 19,2024.The quality of the included literature was assessed using the Joanna Brigg Institute's(JBI)Australian Centre for Evidence-Based Health Care's Quality Assessment Criteria for Qualitative Research,and the results were integrated using the meta-integration methods.Results A total of 17 papers were included in the literature,and 61 findings were extracted,grouped into 10 new categories.These were further synthesized into 4 integrated findings:physical and psychological perceptions of participation in kangaroo mother care;challenges to participation in kangaroo mother care;facilitators of participation in kangaroo mother care;expectations and suggestions for kangaroo mother care.Conclusion Hospital administrators should further improve the management specifications of kangaroo mother care for preterm infants in NICU,optimize resource allocation and strengthen publicity.At the same time,healthcare professionals should actively promote the establishment of peer and family support systems and increase participation in kangaroo mother care to facilitate early recovery of preterm infants in NICU and to continuously promote the improvement of nursing service quality.

Objective:To evaluate the alveolar ridge preservation effect of immediate implantation at extraction site with the im-proved CBCT measuring method.Methods:Eighty patients with extraction site were divided into test group A,B,C and control group.The patients were treated by means of immediate implant placement combined with large flap surgery,guided bone regener-ation(GBR)using mass Bio-Oss bone particles in the group A(the thickness of facial bone wall＜1 mm);The patients were trea-ted by means of immediate implant placement combined without flap surgery and bone graft in the group B(the thickness of facial bone wall ≥1 mm and＜2 mm)and C(the thickness of facial bone wall ≥2 mm),the CGF was implanted in the jumping space only when the thickness of jumping space was＞2 mm.In the control group,the alveolar sockets healed naturally without any in-tervention or treatment.CBCT was taken before surgery,immediately after surgery,and 6 months after surgery to evaluate the height and width of alveolar bone,the thickness of facial bone wall and jumping space.Results:The reduction of alveolar ridge height in group A,B,C and control group was(0.41±0.13,0.94±0.18,0.59±0.12,1.31±0.19)mm,The reduction of alveolar ridge width in group A,B,C and control group was(0.93±0.10,1.48±0.21,1.12±0.17,1.66±0.16)mum.The re-sults of four groups were statistically different(F=177.0,P＜0.001;F=125.3,P＜0.001).The alveolar ridge thickness of facial bone wall in group A,B,C and con-trol group was(0.98±0.25,2.39±0.28)mm,(1.43±0.52,2.10±0.33)mm,(2.17±0.41,2.79±0.27)mm before surgery and six months after immediate implantation.The results of each group were statistically different between before surgery and six months after immediate implantation(t=16.45,P＜0.001;t=7.357,P＜0.001;t=5.488,P＜0.001).Patients in three test groups had the thickness of jumping space＞2 mm and ≤2 mm,and the reduction of alveolar ridge width was(0.78±0.18,0.88±0.17)mm.The results were statistically different(t=17.18,P=0.018).Conclusion:The alveolar ridge preservation was obtained by means of immediate implant placement combined with large flap surgery,guided bone regeneration(GBR)using mass Bio-Oss bone particles at extraction site with the thickness of facial bone wall＜1 mm;The alveolar ridge preservation was obtained without flap surgery and GBR at extraction site with the thickness of facial bone wall≥1 mm.The preservation of soft and hard tissue was better in the axial palatal side of immediate implantation with the thickness of jumping space＞2 mm than that with the thickness of jumping space≤2 mm.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

ObjectiveThis study aims to investigate the effectiveness and potential mechanism of Erxian Decoction （二仙汤） for late-onset depression （LOD）. MethodsForty Wistar male rats of 7-8 weeks were divided into 20 each of normal group and youth depression group. Sixty Wistar male rats of 20 months were divided into 20 each of elder group， LOD group and Erxian Decoction group. The rats in youth depression group were modelled with chronic unpredictable mild stress （CUMS） for 6 weeks to build a depression model， and the elder rats in LOD group and Erxian Decoction group were modelled with CUMS for 6 weeks to build a LOD model， with no interventions in the normal group and the elder group. Gastric administration was carried out at the same time of modelling， rats in Erxian Decoction group were given 8 g/（kg·d） of Erxian Decoction by gavage， and rats in the normal group， youth depression group， elder group， and LOD group were given 4 ml/（kg·d） of pure water by gavage， for 6 weeks in each group. Sugar water preference experiment and forced swimming experiment were used to evaluate the depression-like behaviour of rats， absent field experiment was used to evaluate the spontaneous activity ability of rats， and T-maze experiment was used to evaluate the cognitive function of rats； Western blot assay was used to detect neuronal nuclei （NeuN）， nestin， doublecortin （DCX） in hippocampal tissue， and zonula occludens-l （ZO-1）， folate receptor α （FRα）， reduced folate carrier （RFC）， and protoncoupledfolate transporter （PCFT） protein expression in choroid plexus； immunofluorescence was used to detect the number of double-positive cells for Ki-67/nestin， the number of double-positive cells for 5-bromodeoxyuracil nucleoside （BrdU）/DCX in hippocampal dentate gyrus， and the protein expression of ZO-1， FRα， RFC， and PCFT in choroid plexus tissues； ELISA technique was used to detect plasma， cerebrospinal fluid， 5-methyltetrahydrofolate （5-MTHF） in hippocampal tissues； Pearson correlation analysis was used to correlate the 5-MTHF content in cerebrospinal fluid and hippocampal tissues and the expression of nestin， DCX， and NeuN proteins in hippocampal tissues of rats in youth depression group and LOD group. ResultsCompared with normal group， rats in youth depression group and LOD group showed reduced sugar water preference， reduced total distance travelled in the absent field， reduced number of times through the grid， prolonged forced swimming immobilisation， reduced hippocampal NeuN， nestin and DCX protein expression， reduced number of Ki-67/nestin double-positive cells in hippocampal dentate gyrus， reduced number of BrdU/DCX double-positive cells in hippocampal dentate gyrus， and reduced expression of ZO-1 and FRα proteins and fluorescence intensity （P＜0.05 or P＜0.01）； the correct rate of T-maze on days 3 and 4 in the rats of youth depression group and on days 2 to 4 in the rats of LOD group significantly decreased， and the content of 5-MTHF in the cerebrospinal fluid and hippocampal tissues of the rats of LOD group significantly decreased as well （P＜0.05 or P＜0.01）. Compared with youth depression group， rats in LOD group showed a decrease in total distance travelled in absenteeism， number of times through the grid， a significant decrease in the correct rate of the T-maze on day 1-4， a decrease in NeuN， nestin， DCX protein expression of hippocampal tissue and the number of Ki-67/nestin double-positive cells， BrdU/DCX double-positive cells of hippocampal dentate gyrus （P＜0.05 or P＜0.01）. Compared with LOD group， rats in Erxian Decoction group had elevated sugar-water preference and total distance travelled in absenteeism and number of times through the grid， shorter forced swimming immobility time， significantly higher correct rate of the T-maze on day 3-4， elevated expression of NeuN， nestin， and DCX proteins in hippocampal tissues， increased number of Ki-67/nestin double-positive cells and BrdU/DCX double-positive cells in hippocampal dentate gyrus， and increased 5-MTHF content in cerebrospinal fluid and hippocampal， and ZO-1， FRα， RFC， PCFT protein expression and fluorescence intensity increased in choroid plexus （P＜0.05 or P＜0.01）. Correlation analysis showed that there was a positive correlation between 5-MTHF content in cerebrospinal fluid （r = 0.466）， hippocampal tissue （r = 0.522） and nestin expression in hippocampal tissue （P＜0.05）. ConclusionErxian Decoction could improve depressive-like behaviour and cognitive impairment in LOD model rats， and its mechanism may promote hippocampal neurogenesis by alleviating structural damage to the choroid plexus of the brain tissue， and improving impaired choroid plexus folate transport.