ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 （Ptpn2） on the inflammatory response of mouse alveolar macrophages （MH-S） induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups： the negative control group with an empty vector （NC）， the overexpressed Ptpn2 group （P）， the negative control group with an empty vector + SiO₂ induction （NS）， and the overexpressed Ptpn2 + SiO₂ induction group （PS）. Isobaric tags for relative and absolute quantification （iTRAQ） combined with liquid chromatography-tandem mass spectrometry （LC-MS/MS） were used to screen differential proteins， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor （TNF） α， Gasdermin D （GSDMD）， and Transforming growth factor （TGF）-β1. Western blot was used to detect the protein expression levels of PTPN2， Toll-like receptor 4 （TLR4）， tumor necrosis factor-α （TNF-α）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes （BP）， these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB （NF-κB） signaling， cell activation and signal transduction involved in immune responses， and regulation of receptor signaling pathways by signal transducer and activator of transcription （STAT）， etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway， NF-κB signaling pathway， NOD-like receptor signaling pathway， TGF-β signaling pathway， and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group， the expressions of TNF α， GSDMD， and TGF-β1 in the cells of the NS group increased （P < 0.05）； compared to the NS group， the expression of the aforementioned proteins in the PS group decreased in cellular proteins（P < 0.05）. The results of Western blot showed that compared with the NC group， the protein expression levels of PTPN2， p-NF-κB，MyD88，TLR4，NLRP3，GSDMD，Caspase-1，IL-1β， TGF-βR1， TGF-βR，p-Smad2/3 in the NS group were significantly upregulated （P < 0.05）； compared with the NS group， the expression levels of the aforementioned proteins in the PS group were significantly downregulated （P < 0.05）. ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling， NLRP3 signaling， and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.

OBJECTIVE: To investigate the association between fluid balance trajectories within the first 3 days of intensive care unit (ICU) admission and 28-day mortality as well as the incidence of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients were extracted from the Medical Information Mart of Intensive Care-IV (MIMIC-IV). Group-based trajectory modeling (GBTM) was used to analyze the daily fluid balance of patients within 3 days of ICU admission, and grouping them accordingly. Univariate and multivariate Logistic regression analyses were performed to assess the association between fluid balance trajectory and 28-day mortality and ICU CRRT in SAP patients. RESULTS: A total of 251 SAP patients were included, with 33 deaths within 28 days, and a 28-day mortality of 13.15%; 49 patients (19.52%) continued to receive bedside CRRT after 3 days of ICU admission. The fluid balance on the 3rd day, cumulative fluid balance within 3 days of ICU admission, and incidence of CRRT in the death group were significantly higher than those in the survival group. According to GBTM groups, there were 127 cases in the moderate fluid resuscitation with rapid reduction (MF group), 44 cases in the large fluid resuscitation with rapid reduction (LF group), 20 cases in the moderate fluid resuscitation with slow reduction (MS group), and 60 cases in the small fluid resuscitation with slow reduction (SS group). The cumulative fluid balance within 3 days of ICU admission of the MF group, LF group, MS group, and SS group were 8.60% (5.15%, 11.70%), 16.70% (13.00%, 21.02%), 23.40% (19.38%, 25.45%), and 0.65% (-2.35%, 2.20%), respectively, and the incidence of CRRT during ICU hospitalization were 11.02%, 29.55%, 85.00%, and 8.33%, respectively, with statistically significant differences among the groups (both P < 0.05); the 28-day mortality were 11.02%, 18.18%, 20.00%, and 11.67%, respectively, with no statistically significant difference among the groups (P > 0.05). Kaplan-Meier survival curve analysis showed there was no statistically significant difference in 28-day cumulative survival rate among groups with different fluid balance trajectories (Log-rank test: χ ² = 2.31, P = 0.509). Multivariate Logistic regression analysis showed that cumulative fluid balance within 3 days of ICU admission was an independent risk factor for 28-day mortality [odds ratio (OR) = 1.071, 95% confidence interval (95%CI) was 1.005-1.144, P = 0.040] and CRRT requirement (OR = 1.233, 95%CI was 1.125-1.372, P < 0.001); early aggressive fluid resuscitation on day 1 reduced CRRT risk (OR = 0.866, 95%CI was 0.756-0.978, P = 0.030). CONCLUSIONS Dynamic fluid management is essential in SAP patients. While early aggressive fluid resuscitation may reduce CRRT demand, excessive cumulative fluid balance is associated with increased 28-day mortality and CRRT incidence.
Humans ; Male ; Female ; Middle Aged ; Water-Electrolyte Balance ; Continuous Renal Replacement Therapy ; Intensive Care Units ; Aged ; Adult ; Pancreatitis/mortality* ; Logistic Models ; Retrospective Studies ; Renal Replacement Therapy

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective To observe the analgesic and rehabilitation effects of non μ-opioids anesthesia/analgesia(NΜOA)based on quadratus lumborum block(QLB)in emergency cesarean section under general anesthesia.Methods The retrospective study method was adopted,50 pregnant women undergoing hysterectomy under emergency general anesthesia in Langfang People's Hospital from January 2023 to December 2024 were selected as the study objects.The patients were divided into μ-opioids anesthesia/analgesia(ΜOA)group and NΜOA group according to different anesthesia/analgesia methods,25 cases in each group.ΜOA group received ΜOA;NΜOA group received NΜOA+QLB.Incisional pain and uterine contraction pain numerical rating scale(NRS)at out of the post-anesthesia care unit(T1),intravenous injection of oxytocin(T2),press the palace bottom 24 hours(T3),out of bed activity after operation(T4)and first analgesic time of incision pain,first analgesic time of uterine contraction pain,first no vomiting eating time,first exhaust time was observed and recorded.The incidence of vasoactive agents during the anesthetic period,rescue analgesia,rescue antiemetic,constipation,sleep disturbance after operation within 48 hours after operation were also recorded.Results The NRS scores at T1,T2,T3 and T4 in ΜOA group were significantly higher than those in NΜOA group(incisional pain 3.36±1.25 vs.1.12±0.97,3.68±1.18 vs.2.00±0.91,5.76±1.67 vs.4.20±1.00,4.48±1.29 vs.3.32±0.95;uterine contraction pain 3.72±1.49 vs.1.24±1.05,4.64±1.60 vs.3.04±1.27,7.56±1.71 vs.5.16±1.37,3.56±0.22 vs.2.56±0.16,all P<0.05).The first analgesic time of incision pain,first analgesic time of uterine contraction pain in ΜOA group were significantly less than that in NΜOA group(hours:3.06±2.02 vs.17.48±10.93,2.68±2.22 vs.15.80±11.39,both P<0.05),the first no vomiting eating time,first exhaust time in ΜOA group were significantly longer than those in NΜOA group(hours:8.56±0.57 vs.6.32±0.14,15.44±1.42 vs.10.16±1.14,both P<0.05),the incidence of vasoactive agents,rescue analgesia,rescue antiemetic,constipation,sleep disturbance after operation within 48 hours in ΜOA group were significantly higher than those in NΜOA group[64.0%(16/25)vs.32.0%(8/25),48.0%(12/25)vs.20.0%(5/25),44.0%(11/25)vs.16.0%(4/25),64.0%(16/25)vs.36.0%(9/25),60.0%(15/25)vs.32.0%(8/25),all P<0.05].Conclusion NΜOA based on QLB safely and effectively reduced side effects of μ-opioids and enhanced recovery compared to ΜOA on emergency cesarean section patients undergoing general anesthesia.

Objective To investigate the protective effect and mechanism of adenosine-lidocaine-magnesium sulfate(ALM)resuscita-tion solution against acute lung injury in sepsis were investigated through in vitro and in vivo experiments.Methods ALM resuscitation solution effects on septic lung injury were assessed in SD rats and rat pulmonary micro vascular endothelial cells(PMVEC)in vitro,and the effector mechanism was explored by using network pharmacology combined with molecular biology methods,detecting alterations in nuclear factor kappaB(NF-κB)signaling pathway and inflammatory cytokine key protein expressions.Results Based on in vivo experi-ments,ALM resuscitation solution treatment significantly improved lung histopathological injury in cecal ligation and puncture(CLP)model rats,reduced the lung injury score and lung dry-to-wet ratio(P＜0.01),and significantly suppressed pro-inflammatory cytokine expressions such as that of IL-1β,IL-6,and TNF-α(P＜0.01).Moreover,in vitro experiments confirmed that ALM resuscitation solution significantly reduced p-p65 and p-IκBα protein expressions in LPS-induced PMVEC(P＜0.05),while down-regulating IL-1β,IL-6,and TNF-α protein levels(P＜0.01).Conclusion ALM resuscitation solution exerts a protective effect against acute lung injury in sepsis by inhibiting NF-κB signaling pathway activation and reducing pro-inflammatory cytokine release.

Objective:To investigate the application effect of quadratus lumborum block (QLB) combined with less opioid anesthesia analgesia in laparoscopic total hysterectomy (LTH) in elderly patients with uterine prolapse.Methods:A total of 86 elderly patients with uterine prolapse who received LTH in the Langfang People’s Hospital from Jan. 2021 to Oct. 2023 were prospectively selected and divided into group A ( n=42) and group B ( n=44) according to the random number table method. Group A received transversus abdominis block (TAPB) + general anesthesia, and group B received QLB combined with less opioid anesthesia + general anesthesia. The pain duration at different time points after operation [Numeric Rating Scale (NRS) method to evaluate resting incision and visceral pain] was compared between the two groups. The dosage of opioids and the additional analgesia rate were compared between the two groups. The sleep quality of the two groups before and 72 hours after operation was compared, and the adverse reactions of anesthesia were counted. Results:Compared with 6 h after operation, NRS scores of resting incision pain and visceral pain in the two groups decreased gradually at 12, 24 and 48 h after operation, and it was lower in group B than in group A. There were statistically significant differences between groups ( P<0.05) . Dosage of sufentanil and remifentanil in group B was lower than that in group A, and the postoperative additional analgesia rate in group B (9.09%) was lower than that in group A (28.57%) ( P<0.05) . 72 hours after surgery, the sleep efficiency and total sleep time of patients in both groups were lower than those before surgery, and they were higher in group B than in group A; The awakening time and number of awakenings in both groups were higher than those before surgery, while they were lower in group B than in group A ( P<0.05) . The total incidence of adverse reactions in group B was 4.76% (2/44) , lower than 23.81% (10/42) of group A ( P<0.05) . Conclusion:QLB combined with less opioid anesthesia analgesia can effectively reduce the degree of incision and visceral pain after LTH in elderly patients with uterine prolapse, reduce the amount of opioids used during operation and the rate of additional analgesia, and reduce the incidence of adverse reactions of anesthesia.

Objective:To investigate the application effect of quadratus lumborum block (QLB) combined with less opioid anesthesia analgesia in laparoscopic total hysterectomy (LTH) in elderly patients with uterine prolapse.Methods:A total of 86 elderly patients with uterine prolapse who received LTH in the Langfang People’s Hospital from Jan. 2021 to Oct. 2023 were prospectively selected and divided into group A ( n=42) and group B ( n=44) according to the random number table method. Group A received transversus abdominis block (TAPB) + general anesthesia, and group B received QLB combined with less opioid anesthesia + general anesthesia. The pain duration at different time points after operation [Numeric Rating Scale (NRS) method to evaluate resting incision and visceral pain] was compared between the two groups. The dosage of opioids and the additional analgesia rate were compared between the two groups. The sleep quality of the two groups before and 72 hours after operation was compared, and the adverse reactions of anesthesia were counted. Results:Compared with 6 h after operation, NRS scores of resting incision pain and visceral pain in the two groups decreased gradually at 12, 24 and 48 h after operation, and it was lower in group B than in group A. There were statistically significant differences between groups ( P<0.05) . Dosage of sufentanil and remifentanil in group B was lower than that in group A, and the postoperative additional analgesia rate in group B (9.09%) was lower than that in group A (28.57%) ( P<0.05) . 72 hours after surgery, the sleep efficiency and total sleep time of patients in both groups were lower than those before surgery, and they were higher in group B than in group A; The awakening time and number of awakenings in both groups were higher than those before surgery, while they were lower in group B than in group A ( P<0.05) . The total incidence of adverse reactions in group B was 4.76% (2/44) , lower than 23.81% (10/42) of group A ( P<0.05) . Conclusion:QLB combined with less opioid anesthesia analgesia can effectively reduce the degree of incision and visceral pain after LTH in elderly patients with uterine prolapse, reduce the amount of opioids used during operation and the rate of additional analgesia, and reduce the incidence of adverse reactions of anesthesia.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

The clinical manifestations and genealogic test results of twin sisters with systemic lupus erythematosus (SLE) caused by the homozygous mutation of NCF1 treated at the Department of Pediatrics, Nanfang Hospital, Southern Medical University from May 2021 to January 2024 were reported.Case 1 (a 8-year-old girl) was admitted in May 2021 due to " epistaxis for two times and thrombocytopenia for more than 1 month", presenting tricytopenia, mainly thrombocytopenia.A homozygous mutation of NCF1 gene c. 269G > A (p.R90H) was detected in case 1, and she was subsequently diagnosed with SLE.Case 2 (a 11-year-old girl), the little sister of case 1, was admitted in January 2024 due to " repeated fever for more than 10 days, cough for 2 days, and convulsion once". The manifestations were reduced myelodysplasia, hemophagy accounted for 66%, and perineal ulcer during treatment.She was finally diagnosed with SLE and also had a homozygous mutation of NCF1 gene c. 269G > A (p.R90H).Their parents both carried the mutation.This case provides a reference for pathogenic mutations and phenotypes of NCF1.It suggests that close attention should be paid to the family history of patients in clinical diagnosis of SLE.