Gut microbiota: the indispensable player in neurodegenerative diseases.

As one of the most urgent social and health problems in the world, neurodegenerative diseases have always been of interest to researchers. However, the pathological mechanisms and therapeutic approaches are not achieved. In addition to the established roles of oxidative stress, inflammation and immune response, changes of gut microbiota are also closely related to the pathogenesis of neurodegenerative diseases. Gut microbiota is the central player of the gut-brain axis, the dynamic bidirectional communication pathway between gut microbiota and central nervous system, and emerging insights have confirmed its indispensability in the development of neurodegenerative diseases. In this review, we discuss the complex relationship between gut microbiota and the central nervous system from the perspective of the gut-brain axis; review the mechanism of microbiota for the modulation different neurodegenerative diseases and discuss how different dietary patterns affect neurodegenerative diseases via gut microbiota; and prospect the employment of gut microbiota in the therapeutic approach to those diseases. © 2024 Society of Chemical Industry.

Fabrication of diosmin loaded food-grade bilayer nanoparticles with modified chitosan and soy peptides and antioxidant properties examination.

Diosmin is a flavonoid derived from plants, possessing anti-inflammatory, antioxidant, antidiabetic, neuroprotective and cardiovascular protective properties. However, diosmin has low solubility in water, leading to low bioavailability. In this study, we constructed bilayer nanoparticles with trimethyl chitosan and soy peptides to improve the oral bioaccessibility and bioavailability of diosmin, and determined the characteristics and antioxidant properties of the diosmin-loaded nanoparticles. The results showed that the size of the nanoparticles was around 250 nm with the encapsulation efficiency higher than 97 %, and the nanoparticles were stable under regular conditions. In vitro digestion suggested the nanoparticles could protect diosmin from releasing in gastric digestion but promote the bioaccessibility of diosmin in intestine. Furthermore, the diosmin-loaded nanoparticles presented excellent antioxidant activities in vitro and significantly decreased the Lipopolysaccharides-induced brain Malondialdehyde (MDA) level by oral administration. Therefore, the reported nanoparticles may be an effective platform for improving the oral bioavailability of diosmin.

An independent inter- and intra-observer agreement assessment of Yeom classification for bone cement leakage following vertebroplasty/kyphoplasty.

STUDY DESIGN: An inter- and intra-observer agreement study. BACKGROUND: In recent years, vertebroplasty and kyphoplasty have been widely used in treating osteoporotic vertebral compression fractures (OVCF) though the clinical efficacy of them is still controversial. However, there are also inevitable complications, first and foremost is bone cement leakage (BCL). Yeom classification is commonly used to evaluate BCL. The objective of this study is to assess its reliability and reproducibility, and to explore its clinical application value. METHODS: All 58 patients with BCL following vertebroplasty/kyphoplasty were involved. Six spine surgeons were selected to be evaluators as they were unaware of the identity of the patients and the treatment they received. They classified BCL according to Yeom system, we used kappa (K) to assess the inter- and intra-observer agreement. After 12 weeks, we repeated the analysis. RESULTS: The inter-observer reliability of Yeom classification was substantial with K value of 0.71 (1st assessment) and 0.73 (2nd assessment). The intra-observer reproducibility of Yeom classification was near perfect with K value of 0.88. CONCLUSION: Yeom classification system has substantial inter-observer reliability and near perfect intra-observer reproducibility in BCL following vertebroplasty/kyphoplasty, which can be widely used in clinical care as an appropriate instrument for early observation, mechanism and severity cognition, and prognosis predicting of BCL. Besides, the adding of type M (the mixed type) may improve the classification.

Aroclor 1254 induced inhibitory effects on osteoblast differentiation in murine MC3T3-E1 cells through oxidative stress.

This study aimed to evaluate the osteotoxicity of polychlorinated biphenyls in murine osteoblastic MC3T3-E1 cells, and to explore the underlying mechanism focused on oxidative stress. The cells were exposed to Aroclor 1254 at concentrations of 2.5-20 µmol/L, and then cell viability, oxidative stress, intracellular calcium concentration, osteocalcin content, and calcium nodules formation were measured. Aroclor 1254 reduced cell viability and induced overproduction of intracellular reactive oxygen species in a dose-dependent manner. Activity of superoxide dismutase was decreased, and malondialdehyde content was promoted after exposure. Moreover, inhibitory effects of Aroclor 1254 on calcium metabolism and mineralization of osteoblasts were observed, as indicated by reduction of the intracellular calcium concentration, osteocalcin content, and modules formation rate. The decreased expression of osteocalcin, alkaline phosphatase, bone sialoprotein, and transient receptor potential vanilloid 6 further confirmed the impairment of Aroclor 1254 on calcium homeostasis and osteoblast differentiation. Addition of the antioxidant N-acetyl-L-cysteine partially restored the inhibitory effects on calcium metabolism and mineralization. In general, Aroclor 1254 exposure reduces calcium homeostasis, osteoblast differentiation and bone formation, and oxidative stress plays a vital role in the underlying molecular mechanism of osteotoxicity.

Therapeutic Effects of the Proximal Femoral Nail for the Treatment of Unstable Intertrochanteric Fractures.

Objective: The aim of this study was to analyze the clinical effect of the proximal femoral nail on elderly patients with unstable intertrochanteric fracture and the effect of the proximal femoral nail on serum levels of matrix metalloproteinases (MMPs) and osteoprotegerin (OPG). Methods: The elderly patients with unstable intertrochanteric fracture of the femur admitted to our hospital from January 2017 to January 2021 were studied. 100 patients were randomly divided into two groups: the control group (n = 50) and the observation group (n = 50). The patients in the control group were treated with a proximal femoral locking compression plate. The patients in the observation group were treated with the proximal femoral antirotation intramedullary nail. The clinical therapeutic effects of the two groups and the changes in serum MMPs and OPG levels before and after treatment were analyzed. Results: Compared with the control group, the operation time, postoperative landing time, and fracture healing time of the observation group were significantly shortened, and intraoperative blood loss was significantly reduced (P < 0.05). Compared with the control group, the total effective rate of patients in the observation group was significantly higher (P < 0.05). After treatment, the levels of CRP, IL1ß, IL2, MMP-2, MMP-6, TIMP-1, and RANKL decreased significantly in both groups (P < 0.05), while the levels of OPG increased significantly (P < 0.05). Compared with the control group, the changes in the above indexes were more obvious in the observation group (P < 0.05). Conclusion: The proximal femoral antirotation intramedullary nail has a better therapeutic effect on elderly patients with unstable intertrochanteric fracture, and the level of MMPs and OPG may be related to the treatment process.

Compliance With Epidemic Prevention Guidelines Among Wuhan Citizens Under the Stressors of the COVID-19 Pandemic: A Cross-Sectional Multidistrict Comparative Analysis.

The current study aims to compare compliance with the COVID-19 prevention guidelines among citizens from 13 districts in Wuhan and to explore the influence of individual-level psychological factors and district-level factors on compliance. A total of 811 participants (52% females) from 13 districts in Wuhan were invited to complete surveys regarding demographics, psychosocial factors and compliance with epidemic prevention guidelines. Individual-level characteristics were combined with district-level measures to create multilevel predictive models of compliance with prevention guidelines, and used the Hierarchical Linear Model (HLM) to analyze the data. Findings revealed that there were significant differences in the compliance of citizens from 13 districts of Wuhan (F = 5.65, P < 0.001). Hierarchical linear model analysis revealed that the risk factors case growth rate, COVID-19-related perceived stress, anxiety, significantly negatively predicted compliance. Hope and conscientiousness significantly positively predicted compliance with prevention guidelines, and the negative predictive effect of anxiety disappeared. Overall, we found significant differences in compliance with prevention guidelines among different districts. Risk factors at the individual level have had a negative impact on individuals' compliance with prevention guidelines, but this impact can be mitigated by the positive role of personal protective factors such as conscientiousness and hope.

Xpert MTB/RIF Improves the Prognosis of Multidrug-Resistant Tuberculosis Patients Through Faster Diagnosis and Earlier Targeted Treatment: A Prospective Cohort Study.

Objective: To evaluate the effectiveness of Xpert MTB/RIF in patients with multidrug-resistant tuberculosis (MDR-TB). Methods: Seventy-five patients with MDR-TB were enrolled in this prospective cohort study and were divided into two groups. The observation group were given standardized anti-MDR-TB treatment regimen (6ZAmLfxPtoCs/18ZLfxPtoCs) immediately when they had two positive sputum Xpert MTB/RIF results of RIF resistance. The control group were not given standardized anti-MDR-TB regimen until culture-based drug-susceptibility testing suggested MDR-TB. Treatment effect index, foci absorption, conversion of sputum, treatment outcomes, and adverse reactions were observed. Fisher's exact test and chi-square test were used to compare the differences between groups. Results: Treatment effect index of the observation group significantly out-performed the control group (24/34, 70.6% vs. 17/38, 44.7%, p = 0.027). At the 6th month of treatment course, observation group achieved significantly higher conversion (28/34, 82.3% vs. 23/38, 60.5%, p = 0.042). The foci absorption, cavity change, conversion at the 24th month of course, or treatment outcome between two groups were not statistically different. Conclusion: Xpert MTB/RIF helps MDR-TB patients to start rational treatment regimen earlier and reach earlier sputum conversion.

Posterior cervical full-endoscopic technique for the treatment of cervical spondylotic radiculopathy with foraminal bony stenosis: A retrospective study.

Objective: In the treatment of cervical spondylotic radiculopathy (CSR), spinal endoscopy has been developed vigorously in the past 30 years. However, its effectiveness and subsequent problem of cervical spine stability have always been the controversial hotspots. This study aims to conduct a retrospective study using posterior cervical full-endoscopic technique for the treatment of CSR with foraminal bony stenosis, and evaluate its clinical effect and application value. Methods: All 22 patients treated for CSR with foraminal bony stenosis using posterior cervical full-endoscopic technique were analyzed since Dec 1, 2016, to Apr 30, 2020. The data collection included operation time, length of stay, wound healing, surgical complications, visual analog scale (VAS), Japanese Orthopaedic Association (JOA) scores, intervertebral foramen diameter, intervertebral foramen area and cervical instability. The relevant indicators were observed on admission, at postoperative 1 week and 3 months, and at the last follow-up. Results: The operation time was 141.6 ± 13.7 min. The length of stay was 6.0 ± 2.5 days. VAS and JOA at different time points after operation were decreased compared with before operation (p < 0.05). There were no statistical differences between VAS or JOA at different postoperative time points (p > 0.05). The height, anteroposterior diameter and area of intervertebral foramen after operation were significantly increased compared with before operation (p < 0.05). Conclusion: Posterior cervical full-endoscopic technique shows the advantages of smaller invasion, faster recovery, significant effectiveness and fewer complications in our study. Meanwhile, it has little influence on the ROM and stability of the cervical spine. Therefore, it is a minimally invasive, safe and effective surgical method for the treatment of CSR with foraminal bony stenosis.

The Influence of COVID-19 Pandemic on Physical Health-Psychological Health, Physical Activity, and Overall Well-Being: The Mediating Role of Emotional Regulation.

Background: Highly infectious respiratory disease COVID-19 emerged in Wuhan, China, and spread worldwide. Different measures have been adopted worldwide to contain the COVID-19, and these measures have various impacts on health-related quality of life (HRQoL). This study aimed to assess the impact of the COVID-19 pandemic (CP) and lockdown policy on physical health (PH)-psychological health (PsH), physical activity (PA), and overall well-being (OW) in the context of HRQoL, exploring the mediating role of emotional regulation (ER). Method: The current study was conducted in two provincial cities of China. An online survey was conducted in both the cities to collect the data. After quantifying the data, a total of 2,200 respondents data were analyzed through appropriate statistical techniques. Results: The study results indicate that CP was found significantly and negatively related to PH (ß = -0.157, t = 9.444, p < 0.001). A significant relationship was found between CP and PsH (ß = 0.779, t = 45.013, p < 0.001). The third prediction revealed a significant negative relationship between the CP and OW (ß = -0.080, t = 5.261, p < 0.001). The CP and PA had a significant negative relationship (ß = -0.047, t = 3.351, p < 0.001). Conclusion: The PH, PsH, and OW of the Chinese people were affected due to the CP and lockdown measures. It is suggested that ER intervention reduces the negative psychological impacts for improving quality of life. ER can function one's sentiments in their social environment effectively for quality of life.

Cryogenic Transport Characteristics of P-Type Gate-All-Around Silicon Nanowire MOSFETs.

A 16-nm-Lg p-type Gate-all-around (GAA) silicon nanowire (Si NW) metal oxide semiconductor field effect transistor (MOSFET) was fabricated based on the mainstream bulk fin field-effect transistor (FinFET) technology. The temperature dependence of electrical characteristics for normal MOSFET as well as the quantum transport at cryogenic has been investigated systematically. We demonstrate a good gate-control ability and body effect immunity at cryogenic for the GAA Si NW MOSFETs and observe the transport of two-fold degenerate hole sub-bands in the nanowire (110) channel direction sub-band structure experimentally. In addition, the pronounced ballistic transport characteristics were demonstrated in the GAA Si NW MOSFET. Due to the existence of spacers for the typical MOSFET, the quantum interference was also successfully achieved at lower bias.

[Comparison of the predictive value of tip-apex distance and calcar referenced tip-apex distance in treatment of femoral intertrochanteric fractures with Asian type proximal femoral nail fixation].

OBJECTIVE: To compare the predictive value of the two concepts for complications by comparing the incidences of surgical complications associated with different tip-apex distance (TAD) and calcar referenced tip-apex distance (Cal-TAD) in the treatment of femoral intertrochanteric fractures with Asian type proximal femoral nail (APFN) fixation. METHODS: A total of 188 cases of femoral intertrochanteric fractures treated with APFN fixation between January 2014 and December 2018 were collected according to inclusion criteria. TAD and Cal-TAD were measured on the X-ray film at immediate after operation; the patients were divided into two groups according to the measurement results: <25 mm and ≥25 mm. Gender, age, and fracture side and AO type were recorded. The patients in each group were reviewed whether there was delayed fracture union or nonunion, whether the screw blade moved axially, whether the femoral neck collapsed or even screw blade cut out, whether the internal fixator became loose or broken within 12 months after operation. Then statistical analysis was performed. RESULTS: There were 119 patients with TAD<25 mm and 69 patients with TAD≥25 mm, and 142 patients with Cal-TAD<25 mm and 46 patients with Cal-TAD≥25 mm. There was no significant difference in gender, age, or fracture side and AO type between groups ( P>0.05). During the follow-up, 6 patients (5.04%) with TAD<25 mm, 10 patients (14.49%) with TAD≥25 mm had complications, and 1 patient (0.70%) with Cal-TAD<25 mm and 15 patients (32.61%) with Cal-TAD≥25 mm had complications. There were significant differences in the incidence of complication between the patients with different TAD, between the patients with different Cal-TAD, and between patients with TAD<25 mm and Cal-TAD<25 mm ( P<0.05). CONCLUSION: In the operation of femoral intertrochanteric fracture with APFN fixation, surgical complications can be significantly reduced when TAD or Cal-TAD was controlled within 25 mm, Cal-TAD is more significant in the prediction of postoperative complications.

[Comparison of multi-mode and single-mode intraoperative neurophysiological monitoring in the treatment of severe ossification of the cervical posterior longitudinal ligament with anterior cervical corpectomy with fusion].

OBJECTIVE: To compare the application of multi-mode and single-mode intraoperative neurophysiological monitoring in the treatment of severe ossification of posterior longitudinal ligament of cervical spine with anterior cervical corpectomy with fusion. METHODS: From April 2015 to June 2018, 32 patients with severe ossification of the posterior longitudinal ligament were treated in the Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. There were 21 males and 11 females, aged 45 to 73 years old, with a mean age of 59 years old. The duration of the disease ranged from 6 to 72 months, with a mean of 39 months. The main manifestations were numbness, numbness and weakness of limbs, cotton feeling of foot stepping on lower limbs, instability of standing and walking. With the gradual aggravation of symptoms, quadriplegia, dysfunction of urine and defecation may occur. Patients with ossification of posterior longitudinal ligament of cervical spine were monitored by somatosensory evoked potentials, motor evoked potentials and electromyogram patterns. RESULTS: During the operation, 8 patients had abnormal amplitude of somatosensory evoked potential(SEP); 5 of them had bleeding during anterior cervical decompression procedure and were placed with too much hemostatic cotton, which caused compression of spinal cord and resulted in abnormal SEP waveform. After removal of the hemostatic cotton, SEP waveform returned ot normal; 3 patients had abnormal SEP waveform due to decreased systolic pressure, which was corrected by increased systolic pressure. Twelve patients had abnormal amplitude of motor evoked potential during monitoring, 9 of which were caused by intraoperative mis-contact with nerve root, and turned to normal after timely adjustment of position, 3 of which were caused by intraoperative inhalation of muscle relaxant during surgery. Among 11 patients with abnormal EMG waveform, 9 patients recovered to normal waveform after adjusting operation, 2 patients recovered to normal waveform after short observation, and all patients recovered to normal waveform of motor evoked potential after operation(P<0.05). There were 2 cases of cerebrospinal fluid leakage after operation, which healed spontaneously 7 days after operation, and no complications of spinal cord and nerve occurred in all patients after operation. CONCLUSIONS: In anterior cervical corpectomy with fusion operation for the treatment of severe cervical ossification of posterior longitudinal ligament, various modes of intraoperative neurophysiological monitoring can real-time understand spinal cord and nerve function status, significantly reduce the incidence of spinal cord and nerve injury during operation, and effectively improve the safety of operation.

[Effect of three-dimensional printing-assisted minimally invasive plate osteosynthesis on anti-malrotation for different types of tibial fractures].

OBJECTIVE: To compare the postoperative tibial malrotation between traditional minimally invasive plate osteosynthesis (MIPO) and three-dimensional printing-assisted MIPO (3D-MIPO) for different types of tibial fractures, and explore the change of these differences. METHODS: A prospective randomized controlled trial was conducted. The 120 patients with unilateral tibial fracture who met the selection criteria between January 2016 and October 2018 (40 patients in each of AO types A, B, and C) into the trial group (20 patients, 3D-MIPO) and the control group (20 patients, traditional MIPO) at ratio of 1∶1. There was no significant difference between the two groups (P>0.05) in gender, age, fracture site, and other general information. The bilateral tibial rotation angles were measured on the CT images within 1 week after operation, and the difference of tibial rotation angle between affected and unaffected sides was calculated. The tibial malrotation was defined when the difference exceeded 10°. The degree of tibial rotation and the incidence of malrotation between the two groups in different types of tibial fractures were compared. RESULTS: Postoperative infection occurred in 1 case, and improved after the dressing change and anti-inflammatory treatment. No complications such as loosening and displacement of internal fixation occurred. There was no significant difference in the difference of bilateral tibial rotation angles between the two groups in type A fractures after operation (t=0.559, P=0.580); while in types B and C fractures, the differences of bilateral tibial rotation angles in control group were significantly higher than those in trial group (P<0.05). There was no significant difference in distribution of internal or external rotation between the two groups in types A, B, and C fractures (P>0.05). No malrotation occurred in type A fractures, and there was no significant difference in the incidence of malrotation between the two groups in type B fractures (P=1.000). The incidence of malrotation in control group was significantly higher than that in trial group in type C fractures (P=0.044). CONCLUSION: 3D-MIPO has the same anti-malrotation effect as traditional MIPO for type A tibial fracture, but for types B and C tibial fractures, the anti-malrotation effect of 3D-MIPO is significantly better than that of traditional MIPO. The more complex the fracture type is, the more significant this advantage is.

CRISPR-based rapid and ultra-sensitive diagnostic test for Mycobacterium tuberculosis.

Rapid and simple-to-use diagnostic methods for tuberculosis are urgently needed. Recent development has unveiled the diagnostic power of the CRISPR system in the detection of viral infections. However, its potential use in detecting the Mycobacterium tuberculosis complex (MTB) remained unexplored. We developed a rapid CRISPR-based assay for TB detection and conducted a retrospective cohort study of 179 patients to evaluate the CRISPR-MTB test for identifying MTB in various forms of direct clinical samples. Its diagnostic performance was compared, in parallel with culture and the GeneXpert MTB/RIF assay (Xpert). The CRISPR-MTB test is highly sensitive with a near single-copy sensitivity, demands less sample input and offers shorter turnaround time than Xpert. When evaluated in the clinical cohort of both pulmonary and extra-pulmonary tuberculosis, the CRISPR-MTB test exhibited an overall improved sensitivity over both culture (79% vs 33%) and Xpert (79% vs 66%), without comprise in specificity (62/63, 98%). The CRISPR-MTB test exhibits an improved overall diagnostic performance over culture and Xpert across a variety of sample types, and offers great potential as a new diagnostic technique for both pulmonary and extra-pulmonary tuberculosis.

ZNRF3 contributes to the growth of lung carcinoma via inhibiting Wnt/ß-catenin pathway and is regulated by miR-93.

Lung carcinoma is the most common cancer with increasing morbidity, inefficient therapeutic modality, and poor prognosis, due to the lack of understanding of its related molecular mechanism. ZNRF3 is a newly identified negative regulator of Wnt signaling. In this study, we found that ZNRF3 level is reduced in lung carcinoma compared with normal lung tissue and its expression level is positively correlated with the survival of lung cancer patients. Restoration of ZNRF3 suppressed the proliferation and cell cycle progression of lung cancer cell lines. Suppression of ZNRF3 expression in normal lung cells increased the proliferation rates. In an animal model, ZNRF3 was shown to suppress the growth of lung cancer xenografts. ZNRF3 was shown to negatively regulate the activation of Wnt signaling in lung cancerous and normal cells. Further studies revealed that ZNRF3 is a target of miR-93, an oncogenic microRNA (miRNA) for lung cancer progression. Collectively, we found that miR-93/ZNRF3/Wnt/ß-catenin regulatory network contributes to the growth of lung carcinoma. Targeting this pathway may be a promising strategy for lung cancer therapy.

[A FEASIBILITY STUDY ON TRANSPOSITION OF PROXIMAL MOTOR BRANCHES FROM TIBIAL NERVE TO RECONSTRUCT DEEP FIBULAR NERVE].

OBJECTIVE: To explore the feasibility of transposition of the proximal motor branches from tibial nerve (TN) as direct donors to suture the deep peroneal nerve (DPN) so as to provide a basis for surgical treatment of high fibular nerve injury. METHODS: Nineteen lower limb specimens were selected from 3 donors who experienced high-level amputation (2 left limbs and 1 right limb) and 8 fresh frozen cadavers (8 left limbs and 8 right limbs). The length and diameter of the three motor branches from TN (soleus, medial gastrocnemius, and lateral gastrocnemius) and the distance from the initial points to the branch point of the common peroneal nerve (CPN), as well as the length and diameter of the noninvasive separated bundles of DPN, then the feasibility of tensionless suturing between the donor nerves and the DPN bundle was evaluated. At last, part of the nerve tissue was cut out for HE and Acetylcholine esterase staining observation and the nerve fiber count. RESULTS: Gross anatomic observation indicated the average distance from the initial points of the three donor nerves to the branch point of the CPN was (71.44 ± 2.76) (medial gastrocnemius), (75.66 ± 3.20) (lateral gastrocnemius), and (67.50 ± 3.22) mm (soleus), respectively. The three donor nerves and the DPN bundles had a mean length of (31.09 ± 2.01), (38.44 ± 2.38), (59.18 ± 2.72), and (66.44 ± 2.85) mm and a mean diameter of (1.72 ± 0.08), (1.88 ± 0.08), (2.10 ± 0.10), and (2.14 ± 0.12) mm, respectively. The histological observation showed the above-mentioned four nerve bundles respectively had motor fiber number of 2,032 ± 58, 2.186 ± 24, 3,102 ± 85, and 3,512 ± 112. Soleus nerve had similar diameter and number of motor fibers to DPN bundles (P > 0.05), but the diameter and number of motor fibers of the medial and lateral gastrocnemius were significantly less than those of DPN bundles (P < 0.05). CONCLUSION: All of the three motor branches from TN at popliteal fossa can be used as direct donors to suture the DPN for treating high CPN injuries. The nerve to the soleus muscle should be the first choice.