Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective:To explore the correlation between mechanical complications and paraspinal muscle degeneration following posterior single-segment osteotomy corrective surgery for chronic osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective analysis was conducted on 80 patients who underwent surgery between January 2008 and January 2021 at Peking University Third Hospital. These patients, who developed kyphotic deformity following OVCF, included 17 males and 63 females with a mean age of 63.21±8.07 years (range, 47-77 years). Postoperative mechanical complications included proximal junctional kyphosis (PJK), screw loosening, adjacent segment degeneration (ASD), and distal junctional kyphosis or failure. Patients were compared based on the occurrence of mechanical complications in relation to fat infiltration (FI), relative gross cross-sectional area (rGCSA), and relative functional cross-sectional area (rFCSA) of the paraspinal muscles. Binary logistic regression analysis was used to identify risk factors for postoperative complications.Results:Among the 80 patients, 19 developed PJK, while 61 did not. The PJK group exhibited significantly higher paraspinal muscle FI (0.44±0.05) compared to the non-PJK group (0.38±0.10, P<0.05). Screw loosening occurred in 7 cases, with 73 cases remaining stable. Those with screw loosening demonstrated higher paraspinal muscle FI (0.47±0.05) than those without (0.38±0.09, P<0.05). Thirty patients experienced ASD, while 50 did not. The ASD group had higher paraspinal muscle FI (0.45±0.07) and lower rFCSA (0.09±0.03) compared to the non-ASD group (0.36±0.10 and 0.13±0.06, respectively, P<0.05). Logistic regression analysis indicated that paraspinal muscle FI and rFCSA were not independent risk factors for developing ASD. Twenty-three patients experienced distal junctional kyphosis or failure, while 57 did not; those with complications exhibited higher paraspinal muscle FI (0.48±0.08) and lower rGCSA (0.16±0.04) and rFCSA (0.09±0.03) compared to those without complications (0.37±0.09, 0.20±0.09, and 0.13±0.06, respectively, P<0.05). Logistic regression analysis suggested that paraspinal muscle FI, rGCSA, and rFCSA were not independent risk factors for developing distal junctional kyphosis or failure. Conclusion:Mechanical complications following corrective surgery for chronic OVCF-related kyphosis may be associated with increased paraspinal muscle FI. Additionally, the occurrence of ASD and distal junctional kyphosis or failure may correlate with reduced paraspinal muscle rFCSA

Objective:To systematically evaluate whether the early use of bracing after posterior lumbar fusion has advantages in terms of the improvement of clinical outcomes such as pain, functional disability, fusion rate, and complication rate in patients with lumbar degenerative diseases.Methods:All randomized controlled trials of bracing performed after posterior lumbar fusion in patients with lumbar degenerative diseases were searched in Pubmed, Web of Science, Embase, China national knowledge infrastructure (CNKI) and Wanfang database from January 1990 to May 2022. The data extracted were authors, year of publication, nationality, subject characteristics, sample size, surgical protocol, type and time of bracing, follow-up duration, preoperative and postoperative Oswestry disability index (ODI) and visual analogue scale (VAS), postoperative fusion rate and complication rate. The Cochrane Risk of Bias tool was used to evaluate the risk of bias. The use of fix- or random-effect models was depended on the magnitude of heterogeneity. Data analysis was performed using Stata 17.0 statistical software for meta analysis.Results:A total of five randomized controlled trials were included, all in English, with a total of 362 patients (male 144, female 218). The results of meta-analysis showed that there was no statistically significant difference in the improvement of ODI scores [ MD=1.25, 95% CI(-2.39, 4.88), P=0.501]and VAS scores[ MD=0.21, 95% CI(-0.22, 0.63), P=0.340]between the brace group and the control group after operation. In terms of fusion rate, there was no significant difference between the brace group and the control group[ OR=0.59, 95% CI(0.25, 1.38), P=0.224]. In addition, there was also no significant difference in the incidence of postoperative complications between two groups[ OR=1.12, 95% CI(0.58, 2.15), P=0.735]. Conclusion:The early use of bracing after lumbar fusion has no significant advantages in improving symptoms and functional recovery, fusion rate and surgical complications. The necessity of postoperative bracing after posterior lumbar fusion requires further high-quality research to prove.

Objective To study the invasive histopathological features of papillary thyroid carcinoma(PTC)with tall cell variant(TCV).Methods A retrospective analysis of 19 170 cases of PTC in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from January 2018 to May 2023 was performed to analyze and the clinicopathological features between TCV-PTC group and classic PTC(cPTC)group.Results Pathological results showed 1 380 cases in TCV-PTC group and 15 578 cases in cPTC group.TCV-PTC had higher proportion and(or)mean value in patients'age,extraglandular invasion,nerve invasion,vascular invasion,maximum diameter of cancer focus,multifocality,lymph node metastasis and BRAF mutation,but the proportion of patients with coexistent Hashimoto's thyroiditis was lower than cPTC,and all results had significant difference(P<0.05).Conclusions Compared with the cPTC,TCV-PTC has stronger local invasive characteristics and lymph node metastasis rate,which provides the basis for the subsequent clinical treatment.

Humans ; Spondylitis, Ankylosing/diagnosis* ; Delayed Diagnosis ; East Asian People ; Asian People

Objective To qualitatively analyze the main chemical components in compound Jinqiancao granules by ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Methods XBridge BEH C₁₈ column (2.1 mm×100 mm, 2.5 µm) was used for chromatographic separation. The mobile phase was composed of 0.1% formic acid water and 0.1% formic acid-acetonitrile, gradient elution, and the flow rate was 0.4 ml/min. Mass spectrometry was characterized by Quadrupole time-of-flight mass spectrometry (Q-TOF/MS) and positive ion mode scanning. Results Under the optimized LC/MS condition, 47 components in compound Jinqiancao granules were identified. The isomers were distinguished by software calculation. The source of medicinal materials was assigned. Conclusion A rapid and efficient analytical method was established for the identification of chemical components in compound Jinqiancao granules by UHPLC-Q-TOF/MS.

Objective:To explore the predictive value of vertebral trabecular and endplate HU values on cage subsidence after posterior lumbar interbody fusion (PLIF), hope to provide reference for surgical planning.Methods:All of 72 patients with lumbar disc herniation that underwent PLIF were retrospectively reviewed, who were divided into two groups according to the occurrence of cage subsidence at one-year follow up. Cage subsidence was defined as more than 4 mm subsidence into the vertebrae valuated by CT at one-year follow up. There were 18 patients enrolled into Subsidence group and 54 patients enrolled into N-Subsidence group. The lumbar lordosis, segmental lordosis, intervertebral height, off-bed time, hospital stay, complications, the trabecular and endplate HU values of upper instrumented vertebrae (UIV) and lower instrumented vertebrae (LIV) were compared between the two groups. ROC was used to explore the thresholds of HU values.Results:There were 14 patients presented cage subsidence into the L4, 4 patients presented cage subsidence into the L5. There was no significant difference in lumbar lordosis, segmental lordosis, intervertebral height, off-bed time, hospital stay, or complications between the two groups. Both UIV and LIV trabecular and endplate showed a lower HU value in Subsidence group than those in N-Subsidence group. The most appropriate thresholds of HU value were 146, 172, 307, 254 for trabecular of UIV, trabecular of LIV, lower endplate of UIV, and upper endplate of LIV, respectively.Conclusion:Vertebral trabecular and endplate HU values could effectively predict the cage subsidence after PLIF, patients should be completely informed the risk of cage subsidence and larger cage should be recommended if they presented HU values under the certain threshold.

With the population aging, the prevalence of chronic kidney disease(CKD)is increasing.Frailty is a complex syndrome in the elderly.Elderly CKD patients have higher risks of frailty and cognitive impairment than the general elderly population.In recent years, the relationship between frailty and cognition has gradually attracted the attention of researchers at home and abroad.Cognitive frailty is regarded as a subtype of frailty and has become one of the research hotspots in the field of gerontology.However, there are few studies on the relationship between CKD and cognitive frailty in the elderly.This article reviews research progress on the topic, including the epidemiology, evaluation methods and possible pathogenesis of cognitive frailty in elderly CKD patients.

Objective: To analyze the prospective effect of pre-existing spinal stenosis of adjacent segment on the short-term effectiveness after lumbar fusion surgery. Methods: A prospective comparative study was conducted to divide 183 patients with L 4-S 1 lumbar spinal stenosis who met the selection criteria between July 2015 and December 2017 into two groups according to the status of adjacent segment degeneration (ASD) judged by preoperative disc degeneration and spinal stenosis. There were 98 patients in group A (no degeneration of adjacent segments before operation) and 85 patients in group B (adjacent segments degenerated before operation). There was no significant difference in gender, American Society of Anesthesiologists (ASA) grade, body mass index (BMI), combined spondylolisthesis, and preoperative visual analogue scale (VAS) score of low back pain and leg pain, Japanese Orthopaedic Association (JOA) score, and Oswestry disability index (ODI) score between the two groups ( P>0.05); the age of group A was significantly younger than that of group B ( t=-3.560, P=0.000). The operation time, intraoperative blood loss, hospitalization stay, and perioperative complications were recorded and compared. The VAS score of low back pain and leg pain, JOA score, and ODI score at last follow-up were used to evaluate the effectiveness. The incidence of ASD after operation was compared between the two groups, and logistic regression was used to analyze the independent risk factors affecting the occurrence of ASD after operation. Results: There was no significant difference in operation time, intraoperative blood loss, and hospitalization stay between the two groups ( P>0.05). The incidence of perioperative complications in groups A and B was 13.3% and 20.0%, respectively, with no significant difference ( χ2=1.506, P=0.220). Two groups of patients were followed up, the follow-up time of groups A and B was (24.9±8.8) months and (24.8±7.8) months, respectively, there was no significant difference ( t=0.050, P=0.960). At last follow-up, no adjacent segment disease was found in either group. There was no significant difference in Pfirrmann grade between the two groups at last follow-up ( P>0.05), and there was significant difference in Pfirrmann grade between the two groups before operation and at last follow-up ( P<0.001). At last follow-up, 21 cases (21.4%) in group A and 53 cases (62.4%) in group B had ASD, with significant difference ( χ2=31.652, P=0.000). The main cause of ASD was the severity of adjacent spinal canal stenosis. The clinical scores of the two groups at last follow-up were significantly improved when compared with those before operation ( P<0.05). The JOA score of group A was significantly higher than that of group B at last follow-up ( P<0.05). In group B, the VAS score of low back pain and ODI score in patients with ASD after operation at last follow-up were significantly higher than those in patients without ASD ( P<0.05). logistic regression analysis showed that preoperative pre-existing degeneration and BMI were independent risk factors for ASD after operation ( P<0.05). Conclusion: Pre-existing mild spinal stenosis in adjacent segment can significantly affect the effectiveness, and can significantly increase the risk of ASD early after operation. The main pathological type of ASD was the severity of adjacent segment spinal stenosis. For preoperative assessment of pre-existing degeneration, we should evaluate the overall degeneration of the adjacent segment of the spinal canal, rather than simply evaluating the degeneration of the adjacent disc and facet joints.

Through the questionnaire survey on the current situation of human research ethical management in Beijing medical and health institutions, this paper analyzed the problems existing in ethical management of Beijing medical and health institutions and put forward corresponding countermeasures and suggestions. The results showed that overall status of human research ethical management in Beijing medical and health institutions was satisfying. But the ethical management levels of different types of medical and health institutions were quite different, and medical and health institutions, health family planning administration departments and academic teams should all make corresponding contributions.