ObjectiveTo investigate the efficacy of C-reactive protein （CRP） in predicting the progression to acute-on-chronic liver failure （ACLF） within 90 days after disease onset in patients with acute decompensation （AD） of cirrhosis， and to provide a reference for the early identification of high-risk populations in clinical practice. MethodsA retrospective study was conducted among 906 patients with liver cirrhosis who were hospitalized due to AD in Nanjing Second Hospital from January 1， 2015 to October 31， 2024， and demographic features， AD type， and laboratory markers were collected on admission. The primary endpoint was progression to ACLF within 90 days after admission， and according to the presence or absence of ACLF， the patients were divided into non-ACLF group with 676 patients and ACLF group with 230 patients. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Cox proportional-hazards regression models were used to identify independent predictive factors for ACLF. The receiver operating characteristic （ROC） curve was used to assess the predictive performance of CRP and existing scoring systems （Model for End-Stage Liver Disease ［MELD］， Child-Turcotte-Pugh ［CTP］ score， and Chronic Liver Failure Consortium Acute Decompensation ［CLIF-C AD］ score）， and the restricted cubic spline analysis was used to investigate the nonlinear relationship between CRP and the risk of ACLF. Youden index was used to determine the optimal predictive cut-off value for CRP， and the Kaplan-Meier survival curve was plotted for risk stratification， while the log-rank test was used for survival analysis. ResultsAmong the 906 AD patients， the incidence rate of ACLF was 25.39% within 90 days. The incidence rate of ACLF within 90 days was 45.1% in the 264 patients with bacterial infection and 17.3% in the 642 patients without bacterial infection （χ²=74.791， P<0.001）. Among the 906 patients， 312 patients （34.44%） had acute-on-chronic pre-liver failure （pre-ACLF）， with a significantly higher proportion of patients who progressed to ACLF than those in the non-pre-ACLF group ［60.58% （189/312） vs 6.90% （41/594）， χ²=310.234， P<0.001］. Among the 230 patients with ACLF， there were 102 patients with stable ACLF （44.35%） and 128 patients with unstable ACLF （55.65%）， with a significant difference in CRP between the two groups of patients （U=5 234.500， P<0.001）. The restricted cubic spline analysis showed a significant nonlinear relationship between CRP and the risk of ACLF （P<0.001）. The optimal cut-off value of CRP was determined as 10.16 mg/L based on the Youden index， with a sensitivity of 70.4% and a specificity of 64.5%. The Kaplan-Meier curve analysis showed that the high-risk group with CRP≥10.16 mg/L had a significantly higher event-free survival rate of ACLF within 90 days compared with the low-risk group （P<0.001）. The multivariate Cox regression analysis showed that AD type-hepatic encephalopathy （hazard ratio ［HR］=4.199， 95% confidence interval ［CI］： 3.056 — 5.770， P<0.001）， AD type-bacterial infection （HR=1.826， 95%CI： 1.356 — 2.459， P<0.001）， CRP （≥10.16 mg/L） （HR=2.356， 95%CI： 1.825 — 3.047， P<0.001）， white blood cell count （HR=1.021， 95%CI： 1.002 — 1.041， P=0.035）， hemoglobin （HR=0.994， 95%CI： 0.989 — 0.999， P=0.025）， international normalized ratio （HR=1.657， 95%CI： 1.372 — 2.001， P<0.001）， total bilirubin （HR=1.003， 95%CI： 1.002 — 1.004， P<0.001）， albumin （HR=0.956， 95%CI： 0.926 — 0.986， P=0.004）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， serum sodium （HR=0.976， 95%CI： 0.956 — 0.997， P=0.025）， and lactate dehydrogenase （HR=1.001， 95%CI： 1.001 — 1.002， P<0.001） were all independent predictive factors for progression to ACLF within 90 days. The ROC curve analysis showed that CRP alone had an area under the ROC curve （AUC） of 0.724 （95%CI： 0.685 — 0.763） in predicting ACLF， and CRP+MELD score had the best predictive performance （AUC=0.870， 95%CI： 0.843 — 0.898）， while CRP+CTP score and CRP+CLIF-C AD score had an AUC of 0.852 （95%CI： 0.823 — 0.881） and 0.845 （95%CI： 0.812 — 0.877）， respectively. There was a significant increase in model performance after integration （P<0.05）. ConclusionSerum CRP level on admission is an independent predictive factor for progression to ACLF within 90 days in patients with AD of cirrhosis， and a CRP level of ≥10.16 mg/L can be used as a simple threshold for identifying high-risk patients. Incorporating CRP into existing assessment systems may enhance the early identification of patients at a high risk for ACLF， which provides a reference for clinical intervention.

AIM:To investigate the prevalence of ocular fundus lesions among active-duty military personnel with high myopia and to analyze the associated influencing factors.

METHODS: A cross-sectional study. Subjects included military personnel with high myopia(≤-6.00 D)and elongated axial length(≥26 mm). A systematic evaluation protocol was implemented, consisting of standardized questionnaires, general physical health examinations, and comprehensive ophthalmic assessments. Optical coherence tomography(OCT)was used to screen for fundus lesions in highly myopic subjects, and the prevalence of related lesions was calculated. Axial length, refractive error, best-corrected visual acuity(BCVA), and macular ganglion cell complex(GCC)thickness were measured. Univariate analysis was performed to compare differences in the above parameters between highly myopic subjects with and without concomitant fundus lesions. Multivariate Logistic regression analysis was further applied to identify risk factors for fundus lesions.

RESULTS:A total of 134 male patients(268 eyes)were enrolled, with the mean age of 24.5±3.2 y. Of the 268 eyes, 123 eyes(45.9%)showed positive signs of fundus lesions. Among these, parapapillary blood flow density reduction was found in 84 eyes(31.3%), GCC thinning in 46 eyes(17.2%), drusen in 8 eyes(3.0%), optic disc edema in 7 eyes(2.6%), retinoschisis in 6 eyes(2.2%), and choroidal excavation in 3 eyes(1.1%). BCVA was significantly lower in highly myopic patients with retinoschisis than in those without retinoschisis(P<0.05).Univariate analysis showed that refractive error, axial length, and posterior scleral expansion were associated with the occurrence of fundus lesions(P<0.05). Multivariate Logistic regression analysis revealed that axial length(OR=2.52, 95%CI: 1.67-3.80, P<0.001)and posterior scleral expansion(OR=3.12, 95%CI: 1.65-5.92, P<0.01)were significant risk factors for fundus lesions in highly myopic military personnel.

CONCLUSION: The prevalence of fundus lesions is relatively high among active-duty military personnel with high myopia. Peripapillary flow density reduction and GCC thinning are the most common manifestations in this population. Increased axial length and posterior scleral ectasia are significant contributing factors. It is recommended that OCT be incorporated into routine ophthalmic examinations for these military personnel, thereby providing a basis for the early detection and intervention of fundus lesions.

ObjectiveTo investigate the etiology and clinical features of intrahepatic cholestasis and the diagnostic value of whole exome sequencing （WES） through a retrospective analysis of the medical history， pathological results， and gene sequencing data of 62 patients with unexplained intrahepatic cholestasis. MethodsA retrospective analysis was performed for the clinical data of 480 patients who underwent WES due to unexplained liver function abnormalities in Nanjing Second Hospital from January 2017 to December 2023， among whom 62 patients with unexplained intrahepatic cholestasis were selected based on laboratory data， and a confirmed diagnosis was made based on imaging data， pathological findings， and gene sequencing data. The patients with unexplained intrahepatic cholestasis were analyzed in terms of demographic features， clinical manifestation， etiology spectrum， and genetic profile. ResultsA total of 62 patients with unexplained intrahepatic cholestasis were included， among whom there were 35 male patients and 27 female patients， with a median age of 42 （7 — ‍77） years. WES was used to make a definite diagnosis in 21 patients （33.87%）， among whom the patients with familial intrahepatic cholestasis accounted for the highest proportion of 52.38% （11/21）； genetic metabolic disorders were excluded by WES in 34 patients， with drug-induced liver injury and sepsis-associated liver injury accounting for the highest proportion of 55.88% （19/34）， followed by primary biliary cholangitis and primary sclerosing cholangitis accounting for 20.59% （7/34） and intrahepatic bile duct stones accounting for 17.65% （6/34）， while the patients with a lack of confirmed diagnosis accounted for 11.29% （7/62）. A total of 21 novel mutation sites which were not reported in previous articles were identified in this study. ConclusionGenetic metabolic disorders constitute a significant proportion of unexplained intrahepatic cholestasis， and WES plays a crucial role in the diagnosis of unexplained intrahepatic cholestasis.

Objective To explore the mechanism by which gentiopicroside (GPS) prevents macrophage-mediated hepatic fibrosis by regulating the macrophage migration inhibitory factor (MIF)-secreted phosphoprotein 1 (SPP1) signaling pathway in hepatic stellate cells. Methods LX-2 cells were divided into control group, transforming growth factor β(TGF-β) group, and TGF-β combined with GPS (25, 50, 100, 150 μmol/mL) groups. Cell proliferation was detected by EDU assay, cell invasion was assessed by Transwell^TM assay, and the protein expressions of α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) were measured by Western blot. M1-type macrophage-conditioned medium (M1-CM) was used to treat LX-2 cells in the TGF-β group and TGF-β combined with GPS group. The concentrations of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg1) in the cell supernatant, as well as cell proliferation, invasion ability, and the expressions of α-SMA and COL1A1 were detected. Bioinformatics analysis was performed to identify the target intersections of GPS, hepatic fibrosis, and macrophage-related genes. Drug affinity responsive target stability (DARTS) experiments and Western blot were used to verify the regulatory effect of GPS on MIF. Furthermore, LX-2 cells were divided into control group, TGF-β group, TGF-β combined with M2-CM group, TGF-β and oe-NC combined with M2-CM group, and TGF-β and oe-MIF combined with M2-CM group to analyze the concentrations of iNOS and Arg1 in the cell supernatant, as well as changes in cell proliferation, invasion, and the expressions of α-SMA and COL1A1. LX-2 cells were also divided into control group, TGF-β group, TGF-β combined with oe-NC group, TGF-β combined with oe-MIF group, and TGF-β and oe-MIF combined with GPS group to determine the protein expressions of MIF and SPP1 by Western blot. A rat model of hepatic fibrosis was constructed to explore the potential therapeutic effects of GPS on hepatic fibrosis in vivo. Results Compared with the control group, the proliferation and invasion abilities of LX-2 cells in the TGF-β group were increased, and the protein expressions of α-SMA and COL1A1 were enhanced. GPS intervention inhibited the proliferation and invasion of LX-2 cells under TGF-β conditions and reduced the expressions of α-SMA and COL1A1. Compared with the control group, the concentration of iNOS in the cell supernatant of the TGF-β group was upregulated, while the concentration of Arg1 was decreased. M1-CM treatment further increased the concentration of iNOS, decreased the concentration of Arg1, and promoted cell proliferation and invasion, as well as upregulated the expressions of α-SMA and COL1A1 on the basis of TGF-β intervention. However, GPS could reverse the effects of M1-CM intervention. Bioinformatics analysis revealed that MIF was one of the target intersections of GPS, hepatic fibrosis, and macrophage-related genes, and GPS could target and inhibit its expression. Compared with the TGF-β group, after M2-CM intervention, the concentration of iNOS in the cell supernatant decreased, the concentration of Arg1 increased, the proliferation and invasion abilities of LX-2 cells were reduced, and the expressions of α-SMA and COL1A1 were weakened. However, overexpression of MIF reversed the effects of M2-CM intervention. Western blot results showed that compared with the control group, the protein expressions of MIF and SPP1 were enhanced in the TGF-β group. Overexpression of MIF further enhanced the expressions of MIF and SPP1, while GPS intervention inhibited the expressions of MIF and SPP1. In the animal experiment, GPS intervention treatment alleviated liver injury in rats with hepatic fibrosis and inhibited the expressions of MIF and SPP1, as well as α-SMA and COL1A1 in liver tissue. Conclusion GPS may prevent macrophage-mediated hepatic fibrosis by inhibiting the MIF-SPP1 signaling pathway in hepatic stellate cells.
Hepatic Stellate Cells/metabolism* ; Signal Transduction/drug effects* ; Macrophage Migration-Inhibitory Factors/genetics* ; Liver Cirrhosis/prevention & control* ; Macrophages/drug effects* ; Iridoid Glucosides/pharmacology* ; Humans ; Cell Proliferation/drug effects* ; Animals ; Cell Line ; Collagen Type I/metabolism* ; Collagen Type I, alpha 1 Chain ; Intramolecular Oxidoreductases/genetics* ; Rats ; Transforming Growth Factor beta/pharmacology* ; Actins/metabolism*

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

OBJECTIVE: To investigate the effectiveness of digital three-dimensional (3D) assisted unilateral biportal endoscopy (UBE) in the treatment of highly isolated lumbar disc herniation (LDH) with translaminar approach. METHODS: The clinical data of 59 patients who met the selection criteria and underwent UBE treatment due to highly isolated LDH between January 2022 and December 2023 were retrospectively analyzed. Among them, 25 cases were treated with digital 3D assisted translaminar approach (observation group) and 34 cases were treated with interlaminar approach (control group). There was no significant difference in gender, age, disease duration, surgical segment, and preoperative visual analogue scale (VAS) score and Oswestry disability index (ODI) between the two groups ( P>0.05). The operation time, intraoperative blood loss, and lateral articular surface preservation rate were recorded and compared between the two groups. VAS score and ODI were used to evaluate the improvements of pain and function before operation and at 3 and 6 months after operation. The modified MacNab criteria was used to evaluate the effectiveness at last follow-up. RESULTS: One patient in the control group had dural tear, and the other patients had no nerve injury, infection, dural tear, or other related complications. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). Patients in both groups were followed up 6-13 months, with an average of 8.3 months. The lateral articular surface preservation rate in the observation group was significantly higher than that in the control group ( P<0.05). Three patients in the observation group and 2 patients in the control group had calf muscle venous thrombosis, which was cured after anticoagulant treatment with rivaroxaban and delayed exercise time. There was no recurrence or second operation during the follow-up period. The VAS score and ODI of the two groups at 3 and 6 months after operation significantly improved when compared with those before operation ( P<0.05). There was no significant difference between the two groups at each time point after operation ( P>0.05). At last follow-up, the effectiveness was evaluated according to the modified MacNab criteria, and there was no significant difference in the evaluation grade and excellent and good rate between the two groups ( P>0.05). CONCLUTION UBE via translaminar approach is safe and effective for the treatment of highly isolated LDH, which is beneficial to protect the facet joint, maintain spinal stability, and reduce soft tissue injury. With the assistance of digital 3D technique, preoperative planning can be performed accurately.
Humans ; Intervertebral Disc Displacement/diagnostic imaging* ; Lumbar Vertebrae/diagnostic imaging* ; Male ; Retrospective Studies ; Female ; Endoscopy/methods* ; Treatment Outcome ; Middle Aged ; Adult ; Imaging, Three-Dimensional ; Operative Time ; Pain Measurement

OBJECTIVE: To evaluate early effectiveness of posterior 180-degree decompression via unilateral biportal endoscopy (UBE) in the treatment of lumbar spinal stenosis (LSS) combined with Michigan State University (MSU)-1 lumbar disc herniation (LDH). METHODS: A retrospective analysis was conducted on clinical data from 33 patients with LSS combined with MSU-1 LDH, who met selection criteria and were treated between March 2022 and January 2024. All patients underwent UBE-assisted 180-degree spinal canal decompression. The cohort comprised 17 males and 16 females, aged 37-82 years (mean, 67.1 years). Preoperative presentations included bilateral lower limbs intermittent claudication and radiating pain, with disease duration ranging from 5 to 13 months (mean, 8.5 months). Affected segments included L _{3, 4} in 4 cases, L _{4, 5} in 28 cases, and L ₅, S ₁ in 1 case. LSS was rated as Schizas grade A in 4 cases, grade B in 5 cases, grade C in 13 cases, and grade D in 11 cases. LDH was categorized as MSU-1A in 24 cases, MSU-1B in 2 cases, and MSU-1AB in 7 cases. Intraoperative parameters (operation time, blood loss) and postoperative hospitalization length were recorded. The visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to assess the lower limb pain and functional outcomes after operation. Clinical efficacy was evaluated at last follow-up via modified MacNab criteria. Quantitative radiological assessments included dural sac cross-sectional area (DSCA) measurements and spinal stenosis grading on lumbar MRI. Morphological classification of lumbar canal stenosis was determined according to the Schizas grading, categorized into four grades. RESULTS: The operation time was 60.4-90.8 minutes (mean, 80.3 minutes) and intraoperative blood loss was 13-47 mL (mean, 29.9 mL). The postoperative hospitalization length was 3-5 days (mean, 3.8 days). All patients were followed up 12-16 months (mean, 13.8 months). The VAS score and ODI improved at immediate and 3, 6, and 12 months after operation compared to before operation, and the differences between different time points were significant ( P<0.05). At last follow-up, the clinical efficacy assessed by the modified MacNab criteria were graded as excellent in 23 cases, good in 9 cases, and poor in 1 case, with an excellent and good rate of 96.97%. Postoperative lumbar MRI revealed the significant decompression of the dural sac in 32 cases, with 1 case showing inadequate dural expansion. DSCA measurements confirmed progressive enlargement and stenosis reduction over time. The differences were significant ( P<0.05) before operation, immediately after operation, and at 6 months after operation. At 6 months after operation, Schizas grading of spinal stenosis improved to grade A in 27 cases and grade B in 6 cases. CONCLUSION Posterior 180-degree decompression via UBE is a safe and feasible strategy for treating LSS combined with MSU-1 LDH, achieving effective neural decompression while preserving intervertebral disc integrity.
Humans ; Spinal Stenosis/diagnostic imaging* ; Male ; Female ; Aged ; Lumbar Vertebrae/surgery* ; Middle Aged ; Intervertebral Disc Displacement/complications* ; Decompression, Surgical/methods* ; Retrospective Studies ; Endoscopy/methods* ; Adult ; Aged, 80 and over ; Treatment Outcome