Objective:To compare postoperative anal function recovery between laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis and laparoscopic total colectomy with ileorectal anastomosis for slow transit constipation.Methods:This multicenter retrospective cohort study enrolled patients meeting the following criteria: (1) severe constipation symptoms (<2 bowel movements/week), absent or insignificant defecation urge, abdominal distension, requiring laxatives to maintain bowel movements or laxatives being ineffective; (2) constipation symptoms for over 5 years, ineffective after >2 years of medical treatment, with strong desire for surgery; (3) significantly prolonged colon transit time (>72 hours) without significant gastric or small intestinal transit dysfunction; (4) no organic colonic lesions confirmed by colonoscopy and abdominal CT. Exclusion criteria: (1) patients undergoing open surgery; (2) exclusion of outlet obstruction constipation (e.g., rectocele, rectal prolapse, puborectalis spasm) by functional defecation MRI; (3) comorbid psychiatric disorders; (4) missing clinical data or loss to follow-up (postoperative follow-up <24 months). Based on these criteria, clinical and follow-up data were collected from 220 patients who underwent either laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis (LSC group, n = 115) or laparoscopic total colectomy with ileorectal anastomosis (LTC group, n = 105) for slow transit constipation between January 2013 and December 2022. Subjective anal function (Constipation Severity Score and Wexner Fecal Incontinence Score) and objective anal function (positive rate of rectoanal inhibitory reflex [RAIR] and anorectal manometry) were observed preoperatively and at 6, 12, and 24 months postoperatively. Results:No significant differences were found in baseline characteristics between the two groups (all P >0.05). All surgeries were completed successfully without major significant complications. Subjective anal function assessment: At 24 months postoperatively, Constipation Severity Scores decreased significantly compared to preoperative scores in both groups [LSC group: (25.2±2.8) vs. (2.9±1.8), P <0.001; LTC group: (25.8±2.9) vs. (2.8±1.9), P<0.001]. No significant differences were found between the groups at 6, 12, and 24 months postoperatively (all P>0.05). Wexner Fecal Incontinence Scores at 24 months were significantly lower than those at 6 months in both groups [LSC group: (12.9±1.8) vs. (3.9±2.5), P<0.001; LTC group: (12.6±1.8) vs. (5.4±2.4), P<0.001]. Although no significant difference was found at 6 months ( P = 0.190), the LSC group had significantly lower Wexner scores than the LTC group at 12 and 24 months postoperatively (both P < 0.001). Objective anal function assessment: (1) Positive RAIR rate: Preoperative positive RAIR rates were 33.0% (38/115) in the LSC group and 25.7% (27/105) in the LTC group ( P > 0.05). At 24 months, positive rates increased significantly in both groups [LSC: 66.1% (76/115); LTC: 63.8% (67/105)] compared to preoperative rates (both P<0.001), but no significant differences were found between groups at 6, 12, and 24 months (all P>0.05). (2) Resting pressure (RP) and squeeze pressure (SP): No significant differences were found in preoperative RP and SP between groups (all P>0.05). The LSC group had significantly higher RP and SP than the LTC group at 6 and 12 months postoperatively (all P<0.05), but no significant differences were found at 24 months ( P>0.05). Conclusion:Both laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis and laparoscopic total colectomy with ileorectal anastomosis are safe for patients with slow transit constipation. However, laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis offers superior postoperative anal function recovery.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

OBJECTIVE: To compare the clinical efficacy and complication rates of staged open reduction internal fixation (ORIF) and external fixation combined with limited internal fixation (EFLIF) in the treatment of high-energy Pilon fractures. METHODS: A retrospective selection was conducted on 78 patients diagnosed with high-energy tibial Pilon fractures who received treatment between January 2021 and October 2023. These patients were categorized into the staged ORIF group and the EFLIF group according to their respective treatment protocols. The staged ORIF group comprised 48 patients, including 29 males and 19 females, aged from 33 to 53 years old with a mean age of (43.25±4.67) years old. The time from injury to treatment averaged (6.54±2.21) hours. All patients received staged ORIF treatment. The EFLIF Group consisted of 30 patients, including 18 males and 12 females, aged from 36 to 54 years old with a mean age of (43.37±3.24) years old. The time from injury to treatment averaged (6.87±1.96) hours. All patients received EFLIF treatment. The recovery of ankle joint function, fracture reduction quality, fracture healing time, and surgical-related indicators between two groups were observed and compared six months after surgery. Additionally, the postoperative complications of the two groups were recorded. RESULTS: Both groups of patients were followed up and the duration ranged from 6 to 12 months, with an average of (8.97±1.26) months. At 6-month postoperative follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) score in the ORIF group was (83.15±20.93), which did not show a statistically significant difference compared to the EFLIF group (81.88±20.67), P>0.05. The excellent and good rate of fracture reduction in the staged ORIF group was 33.33% (16/48), which did not show a statistically significant difference compared to the EFLIF group (30.00%, 9/30), P>0.05. The hospitalization duration and fracture healing time in the staged ORIF group were (16.57±1.25) days and (12.14±1.15) weeks, respectively. When compared to the EFLIF group, which demonstrated a hospitalization duration of (15.97±2.16 ) days and a fracture healing time of (12.36±1.17) weeks, no statistically significant differences were observed (P>0.05). The intraoperative blood loss in the staged ORIF group was (76.54±11.65) ml, which was significantly higher than that in the EFLIF group (70.15±10.29) ml, and the difference was statistically significant (P<0.05). The incidence of superficial tissue infection was 2.08%(1/48), which was significantly lower than that observed in the EFLIF group at 16.67% (5/30), and this difference was statistically significant (P<0.05). CONCLUSION Both staged ORIF and EFLIF were effective treatment options for high-energy closed Pilon fractures of the tibia. However, regarding the prevention of superficial tissue infection, staged ORIF demonstrates superior risk control compared to EFLIF.
Humans ; Male ; Female ; Middle Aged ; Adult ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; External Fixators ; Open Fracture Reduction/methods* ; Treatment Outcome

Objective:To investigate the application value of optimized mesenteric defect closure technique in laparoscopic-assisted right hemicolectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 26 patients who underwent laparo-scopic-assisted right hemicolectomy at Changzhi People′s Hospital Affiliated to Changzhi Medical College from May 2023 to June 2024 were collected. There were 11 males and 15 females, aged (65.7±1.8)years. All patients received optimized mesenteric defect closure using a combined extra-corporeal-laparoscopic suturing technique. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical and intraoperative conditions. All 26 patients underwent laparoscopic-assisted right hemicolectomy with optimized mesenteric defect closure. The time of optimized mesenteric defect closure was 9.8(8.8,12.8)minutes, time of digestive tract reconstruction was 10.0(8.7,13.0)minutes, operation time was (164±4)minutes, volume of intraoperative blood loss was 50(50,100)mL. One of the 26 patients had intraoperative mesenteric hematoma, which required no specific intervention. The patient recovered uneventfully and was discharged from hospital. (2) Postoperative conditions. The visual analog scale pain score of 26 patients on postoperative day 1 and day 3 were 5(4,5) and 3(2,3), respectively. Time to postoperative first anal flatus and bowel movement were both 3(3, 4)days. Time to postoperative first intake of liquid diet was 2(2,3)days, duration of postoperative abdominal drainage was 4(3,5)days, and duration of postoperative hospital stay was 9(8,12)days. The number of lymph node dissected in 26 patients was 25(18,27) and the number of positive lymph node was 1(0,2). Cases in stage Ⅰ, stage Ⅱ and stage Ⅲ of tumor TNM staging were 5, 6, 15. (3) Follow-up. All 26 patients were followed up for 15(range, 6?20)months. Of the 26 patients, one case had incom-plete intestinal obstruction on postoperative day 25, which was diagnosed as adhesive intestinal obstruction based on imaging examination and classified as Clavien-Dindo grade Ⅱ. The patient recovered and was discharged after conservative treatment. None of the 26 patients had bleeding, infection of incision, anastomotic leakage, internal hernia, or delayed gastric emptying. There was no tumor recurrence, metastasis or death.Conclusion:The optimized mesenteric defect closure tech-nique in combined extracorporeal-laparoscopic suturing procedure can be used in laparoscopic-assisted right hemicolectomy.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.

BACKGROUND:Studies have demonstrated that postmenopausal osteoporosis is related to female reproductive characteristics and exercise diets,but few studies have demonstrated whether female reproductive characteristics and exercise diets have an effect on vitamin D in postmenopausal women. OBJECTIVE:To investigate the relationship of vitamin D levels with female reproductive characteristics and exercise diets and their influencing factors in postmenopausal women in Beijing. METHODS:Totally 727 postmenopausal women with an age range of 46-75 years old who received on-site questionnaires in 17 communities of Beijing from September 2017 to May 2018 were selected as the study subjects,and the questionnaires included the subjects'basic information and history of menstruation,menopause,pregnancy,and exercise diet.An electrochemiluminescence immunoassay analyzer and its auxiliary reagents were used to determine 25-(OH)D levels.Bone mineral density and T values of the lumbar spine(L1-L4,whole)and both hips(femoral neck,whole)were determined using a dual-energy X-ray bone mineral density detector.The correlation of vitamin D with reproductive characteristics and exercise diet was observed,as well as the influencing factors of vitamin D were analyzed. RESULTS AND CONCLUSION:There were 136 cases(18.7%)in the vitamin D normal group,389 cases(53.5%)in the vitamin D insufficient group,and 202 cases(27.8%)in the vitamin D deficient group.The mean vitamin D level was(15.60±5.85)ng/mL.With the increase of vitamin D level,the bone mineral density value and T value of different parts of the body also increased.Vitamin D level was positively correlated with age at menarche,days of menstrual duration,stage of menopause,activity,diet type,and dietary preference(P<0.05);was negatively correlated with menstrual cycle,age at menopause,and number of childbearing(P<0.05);and had no correlation with age at first conception and number of pregnancies(P>0.05).The results of multifactorial ordered Logistic regression analyses showed that there was a positive correlation between the frequency of drinking dairy products and vitamin D level(P<0.05),and dairy products were a protective factor for vitamin D level.To conclude,vitamin D levels are generally insufficient and bone mineral density values are generally low in postmenopausal women in Beijing.Vitamin D levels are correlated with some reproductive characteristics and exercise diets,and drinking dairy products is a protective factor.Therefore,it is possible to intervene in the dietary situation of postmenopausal women by means of health education about osteoporosis and by increasing vitamin D levels in order to increase bone density values and reduce the prevalence of osteoporosis in the postmenopausal period.

Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.

Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hepatitis C in Henan province from 2012 to 2022.Methods:The case report data on hepatitis C from counties and districts in Henan between 2012 and 2022 were collected. The distribution characteristics were analyzed by descriptive epidemiological methods, and GeoDa1.2 software was used to perform spatial autocorrelation analysis. The spatiotemporal epidemiological analysis was conducted using SaTScan 10.1 software.Results:A total of 274 485 hepatitis C cases were reported in Henan from 2012 to 2022. The reported annual average incidence rate was 25.84/100 000 and showed an overall downward trend from 2012 to 2022 ( Z=-4.05, P<0.001). More cases were reported in women. The cases were mainly aged 40-69 years and farmers. Spatial autocorrelation analysis showed that the reported cases of hepatitis C present spatial clustering during 2012—2022, and the areas with high incidence were mainly distributed in counties or districts of Zhengzhou, Zhumadian, Xuchang, Zhoukou, and Nanyang. One class I clustering area was detected by spatiotemporal scanning, which mainly covered Xuchang, Pingdingshan and the surrounding counties ( LLR=16 117.73, RR=1.81, P<0.001). Conclusion:The reported cases of hepatitis C in Henan Province show an overall downward trend from 2012 to 2022 and present spatiotemporal clustering. The seasonal regularity of the hepatitis C epidemic is not obvious. People aged 40-69 years old and farmers are the key population for prevention and control.

Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hepatitis C in Henan province from 2012 to 2022.Methods:The case report data on hepatitis C from counties and districts in Henan between 2012 and 2022 were collected. The distribution characteristics were analyzed by descriptive epidemiological methods, and GeoDa1.2 software was used to perform spatial autocorrelation analysis. The spatiotemporal epidemiological analysis was conducted using SaTScan 10.1 software.Results:A total of 274 485 hepatitis C cases were reported in Henan from 2012 to 2022. The reported annual average incidence rate was 25.84/100 000 and showed an overall downward trend from 2012 to 2022 ( Z=-4.05, P<0.001). More cases were reported in women. The cases were mainly aged 40-69 years and farmers. Spatial autocorrelation analysis showed that the reported cases of hepatitis C present spatial clustering during 2012—2022, and the areas with high incidence were mainly distributed in counties or districts of Zhengzhou, Zhumadian, Xuchang, Zhoukou, and Nanyang. One class I clustering area was detected by spatiotemporal scanning, which mainly covered Xuchang, Pingdingshan and the surrounding counties ( LLR=16 117.73, RR=1.81, P<0.001). Conclusion:The reported cases of hepatitis C in Henan Province show an overall downward trend from 2012 to 2022 and present spatiotemporal clustering. The seasonal regularity of the hepatitis C epidemic is not obvious. People aged 40-69 years old and farmers are the key population for prevention and control.