ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

OBJECTIVES: Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets. METHODS: Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2. RESULTS: The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2. CONCLUSIONS EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals ; Microglia/metabolism* ; Phagocytosis/physiology* ; Rats, Sprague-Dawley ; Neuralgia/physiopathology* ; Early Growth Response Protein 2/metabolism* ; Male ; Rats ; Spinal Cord/metabolism* ; Sciatic Nerve/injuries*

OBJECTIVE To evaluate the cost-effectiveness of vitamin D analogue for postmenopausal osteoporotic women in China. METHODS A Markov microsimulation model was developed to analyze the clinical and economic outcomes of eldecalcitol， alfacalcidol and calcitriol for postmenopausal osteoporosis from the healthcare system perspective in China. The clinical parameters required for the model were derived from network meta-analysis， while cost and utility data were primarily obtained from the literature. The cycle length was 1 year ， the time horizon was life time， and the willingness-to-pay threshold was 0.5 times the gross domestic product per capita in China in 2023（44 679 yuan/QALY）. Model uncertainty was tested with one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis. RESULTS The quality-adjusted life years （QALYs） for eldecalcitol were calculated to be 12.03 QALYs， which were higher than those for alfacalcidol （11.94 QALYs） and calcitriol （11.92 QALYs）. Meanwhile， the direct medical cost associated with eldecalcitol treatment amounted to 38 805 yuan， which was lower than that of alfacalcidol （45 173 yuan） and calcitriol （45 821 yuan）. The results of the one-way sensitivity analysis showed that the risk ratio of hip fracture and vertebral fracture had a significant impact on the result. The probabilistic sensitivity analysis and scenario analysis showed the robustness of the findings from the base-case analysis. CONCLUSIONS Compared with alfacalcidol and calcitriol， eldecalcitol is likely to be a cost-effective treatment for postmenopausal osteoporotic women in China.

Objective:To compare the incidence of instrumentation-related complications and health-related quality of life following pelvic fixation using iliac screws (IS) or second sacral alar-iliac (S 2AI) screws in adult spinal deformity (ASD). Methods:A retrospective cohort study was conducted on 108 ASD patients who underwent posterior corrective fusion and fixation extending to the pelvis at Nanjing Drum Tower Hospital between September 2010 and April 2021. According to the type of pelvic fixation, patients were divided into an IS group ( n=34; 12 males, 22 females; mean age 53.7±11.1 years, range 28-73 years) and an S 2AI group ( n=74; 23 males, 51 females; mean age 52.8±8.6 years, range 27-72 years). Pre- and post- operative standing anteroposterior and lateral radiographs were evaluated for Cobb angle, coronal balance distance (CBD), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). At 2 years postoperatively, health-related quality of life were assessed using the Scoliosis Research Society-22 questionnaire (SRS-22), Oswestry disability index (ODI), and visual analogue scale (VAS) for pain. Instrumentation failure related to pelvic fixation during follow-up was recorded. Results:All patients completed follow-up. Mean follow-up duration was 28.5±3.6 months (range 24-37 months) in the IS group and 28.1±4.3 months (range 24-43 months) in the S 2AI group. Postoperatively, both groups showed significant improvement in Cobb angle, CBD, TK, LL, SVA, PT, and SS compared to baseline ( P<0.05), whereas PI remained unchanged ( t=0.664, P=0.509; t=1.227, P=0.222). Preoperative PT was greater in the IS group than in the S 2AI group (33.6°±8.7° vs. 29.3°±9.6°, t=2.228, P=0.028). No significant intergroup differences were observed in any other pre- or post- operative radiographic parameters ( P>0.05). Pelvic fixation failure occurred in 31 patients (28.7%, 31/108). Patients with fixation failure had a longer fusion segment extension than those without failure (12.0±2.8 vs. 10.8±2.4 segments; t=2.256, P=0.026). In the IS group, complications comprised 3 cases of screw loosening (8.8%), 2 of screw breakage (5.9%), and 4 of rod fracture within the pelvic region (11.8%), including 1 case with concurrent screw and rod failure. In the S 2AI group, there were 21 cases of screw loosening (28.4%) and 2 of screw breakage (2.7%). Screw loosening was less frequent in the IS group than in the S 2AI group (χ 2=5.154, P=0.023), whereas pelvic rod fracture was more common in the IS group (χ 2=9.041, P=0.003). Screw breakage rates did not differ significantly ( P>0.05). Mean VAS, ODI, and SRS-22 scores in the IS group were 3.2±2.4, 24.9%±18.8%, and 3.2±0.8, respectively; corresponding to 2.5±1.8, 18.9%±10.9%, and 3.3±0.6 in the S 2AI group. ODI was significantly higher in the IS group ( t=2.062, P=0.042), whereas VAS and SRS-22 were comparable ( P>0.05). Among S 2AI patients, VAS and ODI scores did not differ significantly between those with and without screw loosening ( P>0.05). Conclusions:The post-operative incidence of pelvic fixation failure following ASD surgery reached 28.7%. The predominant failure mode with S 2AI was screw loosening, whereas IS was more frequently complicated by rod fracture. Early postoperative health-related quality of life was superior with S 2AI screws compared with iliac screws.

Objective:To investigate the risk factors for postoperative coronal imbalance in patients with type A degenerative scoliosis and to refine the Qiu classification by reclassifying type A patients.Methods:A retrospective analysis was conducted on the clinical data of patients with type A degenerative scoliosis classified by the Qiu classification who underwent corrective surgery at our hospital from January 2017 to April 2022. A total of 69 patients were enrolled in the study, including 3 males and 66 females, with an age of 60.6±6.8 years (range: 47-71 years). Based on the preoperative CBD, type A patients were further divided into three subtypes: Aa with CBD≤1 cm, Ab with CBD>1 cm with C 7 plumb line deviation toward the concave side, and Ac with CBD>1 cm with C 7 plumb line deviation toward the convex side. The incidence of coronal imbalance was compared among subtypes. During follow-up, patients with CBD ≤3 cm were classified as balanced, and those with CBD>3 cm as imbalanced. Radiographic parameters including coronal Cobb's angle (CA), CBD, L 4 tilt angle, L 5 tilt angle, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA) were measured in the standing radiographs preoperatively, 2-weeks postoperatively and 2-years follow-up. Differences in radiographic parameters between balanced and imbalanced groups were compared, and binary logistic regression was used to identify risk factors for postoperative coronal imbalance. Results:In the imbalanced Group (22 patients), there were 6 patients of type Aa (27%), 5 patients of type Ab (23%), and 11 patients of type Ac (50%), and in the balanced Group (47 patients), there were 20 patients of type Aa (43%), 18 patients of type Ab (38%), and 9 patients of type Ae (19%). The difference in subtype distribution between the two groups was significant (χ 2=6.939, P=0.029). The CBD in the imbalanced group was significantly larger than in the balanced group at the 2-years follow-up (4.18±0.86 cm vs. 1.31±0.78 cm, t=-13.813, P<0.001). The preoperative L 4 tilt angle was significantly larger in the imbalanced group compared to the balanced group (23.59°±6.86° vs. 17.64°±8.34°, t=-2.914, P=0.005). And the postoperative and 2-years follow-up L 4 tilt angles were also significantly larger than the balanced group (18.6°±5.5° vs. 11.5°±5.7°, t=-4.904, P<0.001; 18.0°±5.6° vs. 11.1°±5.7°, t=-4.691, P<0.001). Regression analysis identified the Ac type [ OR=3.937, 95% CI(1.07, 14.55), P=0.040] and excessive postoperative L 4 tilt angle [ OR=1.288, 95% CI(1.09, 1.52), P=0.003] as risk factors for postoperative coronal imbalance in type A patients. Conclusions:In the A-type of Qiu classification, patients with preoperative CBD>1 cm and trunk tilting towards the convex side (Ac type), as well as those with a large L 4 tilt angle after surgery, are more likely to experience coronal plane imbalance after surgery.

Objective:To investigate the difference of Roussouly ideal classification in predicting postoperative proximal junctional kyphosis (PJK) between adult degenerative spinal deformity patients with and without pelvic fixation and the potential reasons.Methods:From January 2017 to January 2020, a total of 95 patients (4 males, 91 females; with an average age of 62.03±6.30 years) with degenerative spinal deformities were retrospectively analyzed. There were 35 patients in the non-pelvic group (1 male, 34 females) and 60 patients in the pelvic group (3 males, 57 females). The radiographic parameters included coronal Cobb's angle (CA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), T1 pelvic angle (TPA), and proximal junctional angle (PJA) were measured in the standing radiographs preoperatively, postoperatively at 2 weeks, and 2-year follow-up. Changes in PT and SS were calculated for patients at 2 weeks and the 2-year follow-up. Based on the revised Roussouly classification, 95 patients were classified into different types preoperatively, postoperatively at 2 weeks, and during the 2-year follow-up. Changes in the classification of patients were documented postoperatively at 2 weeks. Roussouly types were determined using preoperative pelvic parameters, and a match was defined when the 2-week postoperative classification aligned with the ideal type. The occurrence of PJK and the relationship with classification matching were recorded in the group. Independent t-tests were used for intergroup comparisons of radiographic parameters, and chi-square tests were employed to assess classification changes and predictive accuracy of the Roussouly classification. Results:Preoperative PT, TPA and SVA in non-pelvic group were significantly smaller than those in pelvic group, and preoperative SS and LL larger than those in pelvic group ( P<0.05). The changes of PT and SS in non-pelvic group were significantly lower than those in pelvic group 2 weeks after surgery ( P<0.05). The proportion of classification changes in the pelvic group was significantly higher than that in the non-pelvic group (60% vs. 34%, χ 2=5.847, P=0.016). Among the 95 patients, a total of 29 experienced PJK during the follow-up, with 3 cases progressing to PJF. The incidence of PJK in mismatched patients was 37% with no significant difference compared with matched patients (19%) (χ 2=3.357, P=0.067). In the sacral spine group of 60 patients, 22 experienced PJK, with 3 cases progressing to PJF. Among them, 19 patients with PJK had a classification mismatch with the ideal classification at 2 weeks postoperatively. The PJK incidence was significantly higher in mismatched patients (45%) compared to matched patients (17%) (χ 2=4.429, P=0.035). In the non-pelvic group, 7 patients developed PJK, with 3 mismatched cases. The PJK incidence in mismatched vs. matched patients was 18% vs. 22%, showing no significant difference (χ 2=0.114, P=0.735). Conclusions:For the patients with degenerative spinal deformity, pelvic fixation leads to a more complete restoration of the ideal Roussouly classification. Restoration of the Roussouly type in patients with pelvic fixation is a reliable predictor of postoperative PJK. However, in patients without pelvic fixation, the alignment with the ideal Roussouly classification does not significantly correlate with PJK development.

A 66-year-old female kidney transplant recipient presented to Shanghai Jiao Tong University Affiliated Renji Hospital on May 24th, 2024 due to recurring intermittent diarrhea for over 16 years. The parasites were found through examination of small intestinal fluid. Small intestinal fluid mNGS combined with blood mNGS confirmed Cyclospora cayetanensis infection. The cause of the diarrhea was clarified. Oral compound sulfamethoxazole was used as treatment, and the patient's diarrhea symptoms improved, and no Cyclospora cayetanensis was found in the small intestinal fluid smear three consecutive times. Parasitic infection factors should be excluded in patients with low immune function and chronic diarrhea. Non-invasive small intestinal fluid smear combined with mNGS detection provides a new method to clarify the cause of chronic diarrhea.

Objective To summarize and analyze the clinical features,imaging manifestations,pathological characteristics,treatment approaches,and prognosis of adrenal anastomotic hemangioma(AH),so as to enhance the clinical understanding of this disease.Methods A retrospective analysis was conducted on 3 adrenal AH patients treated in Tongji Hospital during Jan.2012 and Dec.2024.Relevant literature was reviewed.Results All patients were male,aged 34-56 years,with a maximum tumor diameter of 2.0-5.0 cm.All tumors were solitary.No patients presented with special clinical manifestations.Biochemical tests indicated tumors with no endocrine function.Contrast-enhanced computed tomography showed circular mixed density shadows with uneven edge enhancement.Two patients underwent laparoscopic partial adrenal resection,and one patient received robot-assisted laparoscopic partial adrenal resection.Postoperative pathological results of all three cases indicated AH.Immunohistochemistry showed CD31(+),CD34(+),and ERG(+).No recurrence was found in a postoperative follow-up of 1-45 months.A total of 22 cases of adrenal AH were reported in the literature and our center,with onset age ranging from 34 to 83 years.The patients included 17 males and 5 females,with a maximum tumor diameter of 0.6-8.8 cm.Among them,2 cases were multifocal and the tumors were located in the kidneys,beside kidneys,or in the inferior vena cava.Two cases showed clinical manifestations of lower back pain.During the follow-up of 156 months,no recurrence or metastasis was observed.Conclusion Adrenal AH is a rare benign tumor,which mainly occurs in middle-aged and elderly people with no clinical symptoms and endocrine function.Imaging can easily mistake it for pheochromocytoma or well differentiated vascular sarcoma,and the diagnosis mainly relies on pathological examination.It should be distinguished from pheochromocytoma and well differentiated vascular sarcoma.Surgery is the main treatment method and the prognosis is good.

Objective:To investigate the effect of preoperative continuous fascia iliaca compartment block (FICB) on perioperative opioids dosage and quality of postoperative recovery in elderly patients with frail.Methods:A prospective study method was used. Sixty elderly frail patients underwent selective unilateral femoral head replacement surgery from November 2022 to October 2024 in Sihui People′s Hospital were selected. The patients were divided into control group and FICB group by random digits table method with 30 cases each. The patients in control group did not receive continuous FICB before surgery, and the patients in FICB group received continuous FICB 1 d before surgery. The perioperative use of opioids and analgesic effect, operative time, intraoperative blood loss, postoperative hospital stay, quality of recovery-40 (QoR-40) score at discharge and postoperative complications were compared between the two groups.Results:A total of 57 patients completed the study, with 29 cases in the FICB group and 28 cases in the control group. There were no statistical differences in operative time, intraoperative blood loss and postoperative hospital stay between the two groups ( P>0.05). The sufentanil dosage of patient-controlled analgesia (PCA), perioperative nalbuphine dosage, frequency of perioperative visual analog score (VAS)>4 scores, rate of preoperative rescue analgesia, rate of postoperative rescue analgesia and pressing frequency of PCA in FICB group were significantly lower than those in control group: (94.1 ± 5.4) μg vs. (102.1 ± 6.1) μg, 0 (0, 0) mg vs. 10.0 (0, 20.0) mg, 3.0 (2.0, 5.0) times vs. 5.0 (4.0, 6.0) times, 3.4% (1/29) vs. 32.1% (9/28), 13.8% (4/29) vs. 39.3% (11/28) and 2.0 (1.0, 3.0) times vs. 4.0 (3.0, 5.0) times, and there were statistical differences ( P<0.01 or <0.05). The total QoR-40 score and physical comfort, pain scores in FICB group were significantly higher than those in control group: 156(153, 161) scores vs. 153 (148, 159) scores, 47 (45, 50) scores vs. 45 (43, 47) scores and 30 (29, 31) scores vs. 28 (25, 30) scores, and there were statistical differences ( P<0.05 or <0.01); there were no statistical differences in emotional state, physical independence and psychological support scores between the two groups ( P>0.05). The incidences of dizziness and nausea vomiting in FICB group were significantly lower than those in control group: 13.8% (4/29) vs. 42.9% (12/28) and 10.3% (3/29) vs. 35.7% (10/28), and there were statistical differences ( P<0.05); there were no statistical difference in the incidences of delirium, pulmonary infection and deep vein thrombosis in the lower extremities between the two groups ( P>0.05). Conclusions:Preoperative continuous FICB can reduce perioperative opioids dosage in elderly patients with frail, and improve early stage postoperative recovery quality.

Objective To analyze the effect of LINC00894 on the malignant biological behavior of liver cancer cells by regulating the microRNA(miR)-495-3p/RAS associated binding protein 23(Rab23)axis.Methods Cancer and adjacent tissues of 53 patients with liver cancer who undergoing surgery from January 2023 to November 2023 were collected.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of LINC00894,miR-495-3p and Rab23 in tissues and in vitro cultured cells Huh7,SMMC-7721,HepG2 and L-02.Cells Huh7 were randomly separated into Huh7 group,NC group,si-LINC00894 group,anti-NC group,and anti-miR-495-3p group.CCK-8,flow cytometry and Transwell were used to compare the cell proliferation,apoptosis,migration and invasion of each group.Western blot was used to detect the expression of Rab23 and proliferation-related proteins in cells.The relationship between LINC00894 and miR-495-3p,miR-495-3p and Rab23 was analyzed and verified by dual luciferase reporter gene assay.Results The mRNA and protein expression of LINC00894 and Rab23 were higher in cancer tissues and cells of liver cancer patients,while the mRNA expression of miR-495-3p was lower(P＜0.05).The apoptosis rate of si-LINC00894 group was higher than that of Huh7 group and NC group,and the absorbance at 24 h,48 h,and 72 h,numbers of migrating and invading cells,and expression of Rab23 in cells were lower than those in Huh7 group and NC group(P＜0.05);the absorbance at 24 h,48 h,and 72 h,numbers of migrating and invading cells,and expression of Rab23 in cells in the anti-miR-495-3p group were higher than those in the anti-NC group and si-LINC00894 group,the apoptosis rate of cells was lower than that in the anti NC group and si-LINC00894 group(P＜0.05).The luciferase activity in the WT-LINC00894+miR-495-3p group was lower than that in the WT-LINC00894+miR-NC group(P＜0.05),the luciferase activity in the WT-Rab23+miR-495-3p group was lower than that in the WT-Rab23+miR-NC group(P＜0.05).Conclusion Downregulation of LINC00894 can promote the expression of miR-495-3p,inhibit the expression of Rab23,and thus exert the inhibitory effect on the malignant biological behavior of liver cancer cells.