OBJECTIVE: To explore the effectiveness of triple osteotomy in correcting severe hallux valgus with the first metatarsal pronation deformity. METHODS: A retrospective analysis was conducted on the clinical data of 29 patients (40 feet) with severe hallux valgus accompanied by the first metatarsal pronation deformity, who were admitted between January 2022 and December 2023 and met the selection criteria. There were 8 males (10 feet) and 21 females (30 feet), with an average age of 50.0 years (range, 44-62 years). The disease duration ranged from 5 to 9 years (mean, 6.5 years). All patients underwent triple osteotomy to correct the deformity. The American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analogue scale (VAS) score were used to evaluate joint function and pain before and after operation. Based on pre- and post-operative X-ray films, hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) were measured to evaluate the correction of hallux valgus; the shape classification of the lateral edge of the first metatarsal and the pronation of first metatarsal angle (PFMA) were observed to assess the correction of the first metatarsal pronation deformity. RESULTS: A superficial infection occurred in 1 foot and the incison healed after dressing change; the remaining incisions healed by first intention. All patients were followed up 12-18 months (mean, 12.6 months). Three cases (4 feet) experienced limited movement of the metatarsophalangeal joint after operation, and the joint function recovered after strengthening functional exercises. During follow-up, no recurrence of deformity or secondary metatarsal pain occurred. Compared with preoperative scores, the AOFAS score increased and the VAS score decreased at last follow-up, and the differences were significant ( P<0.05). Radiographic examination showed that the osteotomy achieved bony healing, with the healing time of 2.5-6.2 months (mean, 4.1 months). The hallux valgus deformity was corrected, and the IMA, HVA, and DMAA were significantly smaller at last follow-up when compared with those before operation ( P<0.05). The first metatarsal pronation deformity was also corrected; there was no R-type (R-type for pronation deformity) on the lateral edge of the first metatarsal at last follow-up, and the PFMA decreased compared with preoperative levels ( P<0.05) and was corrected to the normal range. CONCLUSION Triple osteotomy can achieve good effectiveness for correcting severe hallux valgus with the first metatarsal pronation deformity. The functional training of the first metatarsophalangeal joint needs to be strengthened.
Humans ; Hallux Valgus/diagnostic imaging* ; Osteotomy/methods* ; Female ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Metatarsal Bones/diagnostic imaging* ; Treatment Outcome ; Pronation ; Radiography

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + d-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1β (IL-1β) transcription. Through biotin labeling-mediated pull-down and LC-MS/MS analysis, diacylglycerol kinase ζ (DGKζ), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGKζ is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP₃)-Ca²⁺ signaling and subsequent janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1β production and liver failure. DGKζ knockdown/ablation or inhibition significantly impairs the DGKζ-STAT3-IL-1β pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGKζ inhibitor and acts against inflammation in a DGKζ-reliant manner. Taken together, CAM12203 inhibits IL-1β transcription in macrophages by binding to DGKζ and blocking the DGKζ-STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGKζ as a novel therapeutic target.

Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Objective:To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.Methods:Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay. The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Results:Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR. Conclusion:The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.

BACKGROUND:Percutaneous vertebroplasty has become the main treatment method for osteoporotic vertebral compression fractures due to its advantages of convenient operation and low trauma.However,the optimal bone cement-vertebral volume ratio has not been determined. OBJECTIVE:To investigate the effect of bone cement-vertebral volume ratio on percutaneous vertebroplasty for osteoporotic vertebral compression fractures. METHODS:The clinical data of 100 patients with single-stage osteoporotic vertebral compression fractures admitted to Xinjiang Bazhou People's Hospital from July 2019 to July 2022 were retrospectively analyzed.All patients received percutaneous vertebroplasty.According to the bone cement-vertebral volume ratio,they were divided into the low volume group(15%≤ratio≤20%)and the high volume group(20%0.05).The vertebral anterior margin height in the low volume group was lower than that in the high volume group at 3 days and 1 year after surgery(P<0.05).The Cobb angle of the injured vertebrae in the low volume group was higher than that in the high volume group at 3 days and 1 year after surgery(P<0.05).(2)There were 10 H-type and 40 O-type bone cement distributions in the low volume group.There were 36 H-type and 14 O-type bone cement distributions in the high volume group,and there was no significant difference in bone cement distributions between the two groups(P<0.05).The bone cement leakage rate in the high volume group and low volume group was 10%and 6%,respectively.(3)It is indicated that both low and high bone cement-vertebral volume ratios can improve postoperative pain and functional dysfunction,but high bone cement-vertebral volume ratio can improve the morphological recovery of injured vertebral,which may be related to the fact that the distribution of bone cement in this group is more H-type.

Objective To investigate the effect of blood flow restriction combined with low-intensity plyometric jump training(LI-PJT+BFR)on lower limb dynamic postural control of functional ankle instability(FAI)in college students. Methods From March to May,2023,40 FAI college students were recruited from Xi'an Physical Education University,and randomly divided into high-intensity plyometric jump training(HI-PJT,n = 14)group,low-intensity plyomet-ric jump training(LI-PJT,n = 13)group and LI-PJT+BFR group(n = 13).All the groups finished the six-week corresponding training.The maximum voluntary isometric contraction(MVIC)of tibialis anterior,peroneus lon-gus,lateral head of gastrocnemius,gluteus maximus,vastus lateralis,biceps femoris and semitendinosus were measured,and the root mean square(RMS)of electromyography of these muscles was measured during the sin-gle-leg landing(SLL),using wireless surface electromyography before and after intervention.Moreover,they were assessed with Y-balance test and Cumberland Ankle Instability Tool(CAIT). Results MVIC and RMS of the target muscles improved after intervention in all the groups(t>2.218,P<0.05),except MVIC and RMS of peroneus longus,gluteus maximus,biceps femoris and semitendinosus in LI-PJT group,and RMS of peroneus longus in LI-PJT+BFR group;and MVIC and RMS of the target muscles were the least in LI-PJT group(F>3.262,P<0.05),except those of peroneus longus.The extension scores of Y-balance test and the total score improved after intervention(t>2.485,P<0.05),and they were the least in LI-PJT group(F>5.042,P<0.05).The CAIT score improved after intervention(t>5.227,P<0.001),and it was the least in LI-PJT group(F = 4.640,P<0.05). Conclusion LI-PJT+BFR could improve lower limb dynamic postural control of FAI college students,which is similar to HI-PJT.

Objective To explore the differential value of arterial spin labeling(ASL)combined with magnetic resonance spectroscopy(MRS)for postoperative recurrence and pseudoprogression in patients with high-grade glioma.Methods A total of 102 patients with high-grade glioma and new or expanded enhancement lesions after radiotherapy were enrolled.According to the results of pathological examination,they were divided into recurrence group(63 cases)and pseudoprogression group(39 cases).The local metabolites of lesions and their ratios,and local blood flow of lesions were compared between the two groups.The differential value of ASL and MRS for postoperative recurrence and pseudoprogression in patients with high-grade glioma was analyzed.Results Choline(Cho)/creatine(Cr)value,Cho/N-acetylaspartate(NAA)value and relative cerebral blood flow(rCBF)of lesion area in the recurrence group were significantly higher than those in the pseudoprogression group(P＜0.05).Compared with actual prognosis,Kappa values of MRS,ASL and ASL+MRS were 0.344,0.448 and 0.712,respectively(P＜0.05).The sensitivity,specificity and accuracy of MRS,ASL and ASL+MRS(parallel mode)were(66.67％,69.23％,67.65％),(76.19％,69.23％,73.53％)and(88.89％,69.23％,81.37％),respectively.The area under the curve(AUC)of receiver operating characteristic(ROC)curve of Cho/Cr value,Cho/NAA value,rCBF of lesion area and combined detection were 0.657,0.844,0.831 and 0.922,respectively.The AUC of combined detection was significantly higher than that of single index(Z=5.028,2.063,2.242,P＜0.05).Conclusion Compared with single detection,the differential ability of ASL combined with MRS is higher for postoperative recurrence and pseudoprogression in patients with high-grade glioma.

Objective:To compare the efficacy of histopathology(HE),direct immunofluorescence(DIF)and serum anti-BP 180/BP230 antibody ELISA detection(BP 180/BP230)in the diagnosis of oral mucous membrane pemphigoid(MMP).Methods:53 pa-tients with MMP were included.HE,DIF and serum BP 180/230 test results were analyzed and compared.Results:MMP was finally diagnosed in 48 patients by the comprehensive utilization of the 3 techics.There were 8 males(16.7％)and 40 females(83.3％),aged 34-76 years(median age 62 years),with a median duration of 9 months and an interquartile range of 3-12 months.6 patients had ex-traoral sites involvement,including skin(n=3,6.3％),genitalia(n=2,4.2％)and throat(n=1,2.1％).The main site of oral mu-cosa involvement was gingiva(n=40,83.3％),followed by palate(n=22,45.8％),cheek(n=15,31.3％),tongue(n=4,8.3％)and lip(n=3,6.3％).The sensitivity of the routine HE combined with modified biopsy was 83.3％(40/48)and missed diagnosis rate was 16.7％(8/48);the sensitivity of DIF was 85.4％(41/48)and missed diagnosis rate was 14.6％(7/48);the sensitivity of BP180/230 was 47.9％(23/48)and missed diagnosis rate was 52.1％(25/48).The kappa coefficient of agreement between HE and DIFwas0.354(95％CI:0.060,0.648),between BP180/230 ELISA and DIF was-0.112(95％CI:-0.328,0.104),and be-tween HE and BP180/230 ELISA wasO.031(95％CI:-0.181,0.243).Conclusion:HE and DIF have similar effective rate for MMP diagnosis,and they can complement each other.ELISA detection can be used as a supplementary examination for the more accurate di-agnostic of MMP.

Purpose To investigate the clinicopathological features and prognosis of alpha-fetoprotein-producing colorectal carcinoma(AFPCRC).Methods 42 cases of AFPCRC from 2 012 colorectal carcinomas of preoperative serum AFP detected and surgically resected were identified.The clinicopathological data of AFPCRC and other 42 cases of conventional colorectal carcinoma exactly matched for age,gender,stage were also col-lected.Immunohistochemical EnVision method was performed to detect the expression of HER2,MMR,p53,AFP,Glypican3,and SALL4.Cases presenting HER2 2+were further analyzed by fluorescence in situ hybridization.Elastic staining was per-formed in cases with ambiguous extramural venous invasion.The clinicopathlogical features and prognosis between two groups were compared.Cases with AFPCRC were divided into high-AFP group and low-AFP group.The clinicopathological features and prognosis of the two groups were compared.Results AF-PCRC accounted for 2.1％(42/2 012)of colorectal carcinoma in the same period.The frequency of extramural vascular inva-sion and moderate/high grade of tumor budding of AFPCRC was 35.7％and 61.9％,while that of control group was 14.3％and 40.5％respectively.The 5-year survival rate of AFPCRC and control group was 66.8％and 85.1％respectively.The differ-ence of aforementioned clinicopathological features between 2 groups was significant(P＜0.05).The proportion of tumor in rectum in the high-AFP group was significantly higher than that in the low-AFP group(61.9％vs 23.8％,P＜0.05).Conclu-sion AFPCRC is a rare subset of colorectal carcinoma,which has a propensity for extramural vessel invasion,moderate-or high-grade of tumor budding and poor prognosis.