Risk Factors for Surgical Treatment of Lumbar Degenerative Disc Disease in Middle-aged and Older Women: A Prospective Case-Control Study of 2370 Subjects.

OBJECTIVE: Given the distinct physiological and societal traits between women and men, we propose that there are distinct risk factors for lumbar degenerative disc disease surgeries, including lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS), in middle-aged and older populations. However, few studies have focused on middle-aged and older women. This study aims to identify these risk factors specifically in this population. METHODS: In this case-control study, the study group comprised 1202 women aged ≥ 45 years who underwent operative treatment of lumbar degenerative disc disease (LDH, n = 825; LSS, n = 377), and the control group comprised 1168 women without lumbar disease who visited a health examination clinic during the same period. The study factors included demographics (age, body mass index [BMI], smoking, labor intensity, and genetic history), female-specific factors (menopausal status, number of deliveries, cesarean section, and simple hysterectomy), surgical history (number of abdominal surgeries, hip joint surgery, knee joint surgery, and thyroidectomy), and systemic diseases (hypercholesterolemia, hypertriglyceridemia, hyper-low-density lipoprotein cholesterolemia, hypertension, diabetes, cardiovascular disease, and cerebrovascular disease). Multivariate binary logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) of associated factors. RESULTS: The risk factors for surgical treatment of LDH in middle-aged and older women included BMI (OR = 1.603), labor intensity (OR = 1.189), genetic history (OR = 2.212), number of deliveries (OR = 1.736), simple hysterectomy (OR = 2.511), hypertriglyceridemia (OR = 1.932), and hyper-low-density lipoprotein cholesterolemia (OR = 2.662). For surgical treatment of LSS, the risk factors were age (OR = 1.889), BMI (OR = 1.671), genetic history (OR = 2.134), number of deliveries (OR = 2.962), simple hysterectomy (OR = 1.968), knee joint surgery (OR = 2.527), hypertriglyceridemia (OR = 1.476), hyper-low-density lipoprotein cholesterolemia (OR = 2.413), and diabetes (OR = 1.643). Cerebrovascular disease was a protective factor against surgery for LDH (OR = 0.267). CONCLUSIONS: BMI, genetic history, number of deliveries, simple hysterectomy, hypertriglyceridemia, and hyper-low-density lipoprotein cholesterolemia were independent risk factors for surgical treatment of both LDH and LSS in middle-aged and older women. Two disparities were found: labor intensity was a risk factor for LDH patients, and knee joint surgery and diabetes were risk factors for LSS patients.

hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-κB signaling in an NMO mouse model.

Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin αvß3/NF-κB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO.

Scalar topological photonic nested meta-crystals and skyrmion surface states in the light cone continuum.

Topological photonics is rapidly expanding. However, discovering three-dimensional topological electromagnetic systems can be more challenging than electronic systems for two reasons. First, the vectorial nature of electromagnetic waves results in complicated band dispersions, and simple tight-binding-type predictions usually fail. Second, topological electromagnetic surface modes inside the light cone have very low quality factors (Q factors). Here, we propose the concept of scalar topological photonics to address these challenges. Our approach is experimentally validated by employing a nested meta-crystal configuration using connected coaxial waveguides. They exhibit scalar-wave-like band dispersions, making the search for photonic topological phases an easier task. Their surface states have skyrmion-like electric field distributions, resulting in a whole, bright surface state band inside the light cone continuum. As such, the topological surface states in our three-dimensional nested crystals can be exposed to air, making such systems well-suited for practical applications.

[Electroacupuncture mitigates hyperlipidemia via improving cholesterol metabolism mediated by SCAP/SREBP-2 signaling in liver tissue in rats].

OBJECTIVE: To explore the effect of electroacupuncture (EA) on sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP)/ SREBP-2 signaling and the expressions of its downstream cholesterol metabolism related molecules 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and low-density lipoprotein receptor (LDLR) in the liver tissue in rats with hyperlipidemia (HLP), so as to reveal its mechanisms underlying improvement of HLP. METHODS: Male SD rats were randomly divided into normal control, HLP model and EA groups (n=10/group). The HLP model was established by feeding the rats with high-fat diet for 28 d. Rats in the EA group received EA stimulation (2 Hz/100 Hz, 2 mA) at "Fenglong" (ST40) and "Yinlingquan"(SP9) for 30 min, once daily for 28 d. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) in the serum, the activity of glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) were detected by automatic biochemical analysis. The content of TC in the liver tissue was detected using high performance liquid chromatography. The mRNA and protein expression levels of SCAP, SREBP-2, HMGCR, PCSK9 and LDLR in the liver tissue were measured by using quantitative real-time PCR and Western blot, respectively. The immunofluorescence density of liver SCAP was determined by using immunofluorescence histochemistry. RESULTS: Compared with the normal control group, the contents of liver TC, serum TC, LDL-C, the activities of AST and ALT, and the mRNA and protein expression levels of SCAP, SREBP-2, HMGCR, PCSK9 as well as SCAP immunoactivity were significantly increased (P<0.01), while the LDLR mRNA and protein levels were markedly decreased (P<0.01) in the model group. In comparison with the model group, the contents of liver TC， serum TC, LDL-C, the activities of AST and ALT and the expression of SCAP, SREBP-2, HMGCR, PCSK9 mRNAs and proteins and SCAP immunoactivity were considerably decreased in the EA group (P<0.01), while the LDLR protein level was evidently increased in the EA group (P<0.05). CONCLUSION: EA intervention can inhibit the synthesis of cholesterol in the liver and thus improve hyperlipidemia in HLP rats, which may be realized by down-regulating the protein and mRNA expressions of hepatic SCAP/SREBP-2, HMGCR and PCSK9, and up-regulating LDLR protein.

Analysis of the value of artificial intelligence combined with musculoskeletal ultrasound in the differential diagnosis of pain rehabilitation of scapulohumeral periarthritis.

To explore the value of artificial intelligence combined with musculoskeletal ultrasound in the differential diagnosis of pain rehabilitation of scapulohumeral periarthritis. A total of 165 patients with periarthritis of the shoulder, who were admitted to our hospital from January 2020 to January 2022, were selected. Konica SONIMAGE HS1 PLUS color Doppler ultrasound diagnostic instrument was used to detect muscles and bones of patients with scapulohumeral periarthritis. This study proposed an intelligent clustering analysis algorithm with musculoskeletal ultrasound parameters. The neural network was trained on a GeForce RTX 3060 with the Adam W optimizer, a batch size of 12, and an initial learning rate of 5E-4. Each batch of 2 types of trained samples was input into the network in a specific proportion. Pain was assessed on a 10-point visual analogue scale. On the affected side of scapulohumeral periarthritis, the mild pain group showed thickening of the shoulder posterior capsule (2.02 ± 0.72) mm with clear edges. In the moderate pain group, the thickness of the shoulder posterior capsule gradually narrowed (1.01 ± 0.38) mm and became even thinner than that of the unaffected side, with irregular and blurred edges. In the severe pain group, the thickness of the shoulder posterior capsule largely returned to normal (1.21 ± 0.42) mm, and the edge was clear. Multivariate logistic regression showed that in addition to musculoskeletal ultrasound parameters, the length of service, work nature, and the busy degree of work of patients with periarthritis of the shoulder were significant factors that influenced shoulder periarthritis pain (P < .05). The performance of the proposed intelligent auscultation algorithm was further examined in a clinical setting, in which we used 165 clinical musculoskeletal ultrasound samples (including 81 positive and 84 negative samples) as a test set. The accuracy, sensitivity, and specificity were 0.833, 0.872, and 0.801, respectively. Musculoskeletal ultrasound combined with artificial intelligence algorithm is a new diagnostic and staging tool for scapulohumeral periarthritis.

Photonic Z_{2} Topological Anderson Insulators.

That disorder can induce nontrivial topology is a surprising discovery in topological physics. As a typical example, Chern topological Anderson insulators (TAIs) have been realized in photonic systems, where the topological phases exist without symmetry protection. In this Letter, by taking transverse magnetic and transverse electric polarizations as pseudospin degrees of freedom, we theoretically propose a scheme to realize disorder-induced symmetry-protected topological phase transitions in two-dimensional photonic crystals with a combined time-reversal, mirror, and duality symmetry T_{f}=TM_{z}D. In particular, we demonstrate that the disorder-induced symmetry-protected topological phase persists even without pseudospin conservation, thereby realizing a photonic Z_{2} TAI, in contrast to a Z-classified quantum spin Hall (QSH) TAI with decoupled spins. By formulating a new scattering approach, we show that the topology of both the QSH and Z_{2} TAIs can be manifested by the accumulated spin rotations of the reflected waves from the photonic crystals. Using a transmission structure, we also illustrate the trivialization of a disordered QSH phase with an even integer topological index caused by spin coupling.

Safety and immunogenicity of a quadrivalent, inactivated, split-virion influenza vaccine (IIV4-W) in healthy people aged 3-60 years: a phase III randomized clinical noninferiority trial.

BACKGROUND: A quadrivalent split influenza vaccine IIV4-W against both influenza A and B viruses is urgently needed. METHODS: To evaluate the safety and immunogenicity of IIV4-W in people aged 3-60 years, 2400 participants recruited in a double-blind phase III trial and were randomly assigned to the IIV4-W, TIV1 and TIV2 groups. The immunogenicity indicators were measured at 28 days postvaccination and for 180 days for safety follow-up. RESULTS: Adverse events (AEs) occurred in 162 (20.28%), 116 (14.55%) and 123 (15.41%) participants in the IIV4-W, TIV1 and TIV2 groups, respectively. All these AEs were mild and self-limiting, and no serious AEs related to the vaccines were observed. IIV4-W elicited a non-inferior immune response for matched strains (the lower limit of 95% CI for GMT ratio >0.67, for SCR and SPR difference >-10%) and superior immune response for the additional B strains (the lower limit of 95% CI for GMT ratio >1.5, for SCR difference >10%) versus TIVs. The lower limit of the 95% confidence interval of the GMT increase fold, the seroconversion rate and the seroprotection rate exceeded 2.5, 40% and 70% for the four strains in IIV4-W respectively. CONCLUSIONS: IIV4-W was noninferior to the TIV-matched strains and was superior to the additional B strain. IIV4-W was safe in the participants and elicited high antibody titers.

Four-band non-Abelian topological insulator and its experimental realization.

Very recently, increasing attention has been focused on non-Abelian topological charges, e.g., the quaternion group Q8. Different from Abelian topological band insulators, these systems involve multiple entangled bulk bandgaps and support nontrivial edge states that manifest the non-Abelian topological features. Furthermore, a system with an even or odd number of bands will exhibit a significant difference in non-Abelian topological classification. To date, there has been scant research investigating even-band non-Abelian topological insulators. Here, we both theoretically explore and experimentally realize a four-band PT (inversion and time-reversal) symmetric system, where two new classes of topological charges as well as edge states are comprehensively studied. We illustrate their difference in the four-dimensional (4D) rotation sense on the stereographically projected Clifford tori. We show the evolution of the bulk topology by extending the 1D Hamiltonian onto a 2D plane and provide the accompanying edge state distributions following an analytical method. Our work presents an exhaustive study of four-band non-Abelian topological insulators and paves the way towards other even-band systems.

Study on the Algorithm of Three-Dimensional Surface Residual Material Height of Nano-ZrO2 Ceramics under Ultra-Precision Grinding.

A large number of studies have shown that the height of a residual material is the key factor affecting the surface quality of ultra-precision grinding. However, the grinding process contains several random factors, such as the randomness of grinding particle size and the random distribution of grinding particles, which cause the complexity of the material removal process. In this study, taking the Nano-ZrO2 as an example, the removal process of surface materials in ultra-precision grinding of hard and brittle materials was analyzed by probability. A new calculation method for the height of surface residual materials in ultra-precision grinding of Nano-ZrO2 was proposed, and the prediction model of the three-dimensional roughness Sa and Sq were established by using this calculation method. The simulation and experimental results show that this calculation method can obtain the more accurate surface residual material height value which accords with the characteristics of three-dimensional roughness sampling, which provides a theoretical reference for the analysis of the material removal process and the surface quality evaluation of ultra-precision grinding of hard and brittle materials.

Experimental observation of non-Abelian topological charges and edge states.

In the last few decades, topological phase1-11 has emerged as a new classification of matter states beyond the Ginzburg-Landau symmetry-breaking paradigm. The underlying global invariant is usually well characterized by integers, such as Chern numbers or winding numbers-the Abelian charges12-15. Very recently, researchers proposed the notion of non-Abelian topological charges16-19, which possess non-commutative and fruitful braiding structures with multiple (more than one) bandgaps tangled together. Here we experimentally observe the non-Abelian topological charges in a time-reversal and inversion-symmetric transmission line network. The quaternion-valued non-Abelian topological charges are clearly mapped onto an eigenstate-frame sphere. Moreover, we find a non-Abelian quotient relation that provides a global perspective on the distribution of edge/domain-wall states. Our work opens the door towards characterization and manipulation of non-Abelian topological charges, which may lead to interesting observables such as trajectory-dependent Dirac/Weyl node collisions in two-dimensional systems16,17,20, admissible nodal line configurations in three dimensions16,19,20, and may provide insight into certain strongly correlated phases of twisted bilayer graphene21.

Topological One-Way Large-Area Waveguide States in Magnetic Photonic Crystals.

We have theoretically and experimentally achieved large-area one-way transport by using heterostructures consisting of a domain of an ordinary photonic crystal sandwiched between two domains of magnetic photonic crystals. The nonmagnetized domain carries two orthogonal one-way waveguide states which have amplitude uniformly distributed over a large area. We show that such one-way waveguide states can be used to abruptly narrow the beam width of an extended state to concentrate energy, and the transport is robust against different kinds of defects and imperfections. They are also immune to the Anderson-type localization when large randomness is introduced.

[Effect of electroacupuncture on insulin sensitivity and TLR4/ IκBα/ NF-κB signaling in hypothalamus of obese rats with insulin resistance].

OBJECTIVE: To observe the effects of electroacupuncture on the hypothalamic Toll-like receptor 4 (TLR4)/ inhibitor nuclear factor kappa-B α(IκBα)/nuclear factor-κB (NF-κB) signaling pathway in obese insulin resistance (OIR) rats，so as to explore the mechanism of EA underlying improving of insulin resistance. METHODS: Rats were randomly divided into normal, model and EA groups, with 8 rats in each group. The rat model of OIR was established by feeding with high-fat diet for 8 weeks. EA(2 Hz，1 mA)was applied to unilateral"Zusanli"(ST36),"Fenglong"(ST40),"Zhongwan"(CV12)and"Guanyuan"(CV4)for 10 min, 3 times a week for 8 weeks. The body mass, fasting blood glucose(FBG) and postprandial blood glucose (PBG) were measured before and after 2、4、6、8 weeks' intervention. An intraperitoneal injection glucose tolerance test and hyperglycemic clamps were applied to test insulin resistance. The expression of TLR4、p-IκBα、NF-κB p65、TNF-α、IL-1ß mRNA and protein in hypothalamus was detected by quantitative real-time PCR and Western blot, separately. RESULTS: Compared with the normal group, the body mass and PBG of the model group were significantly increased (P<0.01); glucose infusion rate(GIR) was significantly reduced (P<0.01); in the IPGTT test, the increase in blood glucose was significantly greater after 90 and 120 min of glucose injection(P<0.01); the hypothalamus TLR4, NF-κB p65，p-IκBα, TNF-α, IL-1ß mRNA and protein expressions were all significantly increased (P<0.01). After EA intervention, the body weight and PBG were significantly down-regulated after 6 weeks and 2 weeks of intervention (P<0.05, P<0.01); GIR were significantly up-regulated after 8 weeks of intervention (P<0.05); In the IPGTT test, the increase in blood glucose 60 min after glucose injection was significantly down-regulated (P<0.05); hypothalamus TLR4, NF-κB p65，p-IκBα, TNF-α, IL -1ß mRNA and protein expression were significantly down-regulated (P<0.01). CONCLUSION: EA can reduce the body weight of OIR rats and improve IR, which may be related to down-regulating the hypothalamic TLR4/IκBα/NF-κB signaling pathway.

Exceptional nexus with a hybrid topological invariant.

Branch-point singularities known as exceptional points (EPs), which carry a nonzero topological charge, can emerge in non-Hermitian systems. We demonstrate with both theory and acoustic experiments an "exceptional nexus" (EX), which is not only a higher-order EP but also the cusp singularity of multiple exceptional arcs (EAs). Because the parameter space is segmented by the EAs, the EX possesses a hybrid topological invariant (HTI), which consists of distinct winding numbers associated with Berry phases accumulated by cyclic paths on different complex planes. The HTI is experimentally characterized by measuring the critical behaviors of the wave functions. Our findings constitute a major advance in the fundamental understanding of non-Hermitian systems and their topology, possibly opening new avenues for applications.

Bibliometric Analysis of Scientific Publications on Spinal Cord Stimulation in the Past Two Decades.

BACKGROUND: Spinal cord stimulation (SCS), a common invasive neuromodulation technique, induces pain relief via electrical stimulation of the dorsal column of the spinal cord. To present an overview of research publications on SCS, a bibliometric analysis of scientific publications from 1998 to 2017 was performed. METHODS: The relevant data were obtained from the Web of Science and PubMed database. These articles were classified into several categories, such as total number, countries, institutions, authors, and citations reports. The analysis of co-occurrence key words was handled by VOSviewer software. RESULTS: We found that there existed an increasing trend in the number of publications on SCS between 1998 and 2017. Among these countries, the United States published the largest number of papers in the past 20 years. Case Western Reserve University in the United States contributed the most publications. Among all research categories, neuroscience neurology was the most common area. In addition, regarding article types, basic research comprised a great proportion of the total papers on SCS in the PubMed database. The author V. Reggie Edgerton from the United States was the most-frequent contributor among the authors. The results showed that "spinal cord," "stimulation," and "pain" were the most common key words in the past 20 years. CONCLUSIONS: This bibliometric analysis first provides a basic overview of research publications on SCS published during the last 2 decades. Considering the expanded indications of SCS, there are a lot of things to do, and various countries should increase support to complete high-quality SCS studies.

Effects of intensity of electroacupuncture on chronic pain in patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Conditioned pain modulation (CPM) is impaired in people with chronic pain such as knee osteoarthritis (KOA). The purpose of this randomized, controlled clinical trial was to investigate whether strong electroacupuncture (EA) was more effective on chronic pain by strengthening the CPM function than weak EA or sham EA in patients with KOA. METHODS: In this multicenter, three-arm parallel, single-blind randomized controlled trial, 301 patients with KOA were randomly assigned. Patients were randomized into three groups based on EA current intensity: strong EA (> 2 mA), weak EA (< 0.5 mA), and sham EA (non-acupoint). Treatments consisted of five sessions per week, for 2 weeks. Primary outcome measures were visual analog scale (VAS), CPM function, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Three hundred one patients with KOA were randomly assigned, among which 271 (90.0%) completed the study (mean age 63.93 years old). One week of EA had a clinically important improvement in VAS and WOMAC but not in CPM function. After 2 weeks treatment, EA improved VAS, CPM, and WOMAC compared with baseline. Compared with sham EA, weak EA (3.8; 95% CI 3.45, 4.15; P < .01) and strong EA (13.54; 95% CI 13.23, 13.85; P < .01) were better in improving CPM function. Compared with weak EA, strong EA was better in enhancing CPM function (9.73; 95% CI 9.44, 10.02; P < .01), as well as in reducing VAS and total WOMAC score. CONCLUSION: EA should be administered for at least 2 weeks to exert a clinically important effect on improving CPM function of KOA patients. Strong EA is better than weak or sham EA in alleviating pain intensity and inhibiting chronic pain. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry ( ChiCTR-ICR-14005411 ), registered on 31 October 2014.

[Randomized controlled trial of internal heat-type acupuncture needle therapy in the treatment of post-stroke shoulder pain].

OBJECTIVE: To evaluate the effectiveness and safety of internal heat-type acupuncture needle (IHTAN) the-rapy in the treatment of post-stroke shoulder pain in apopletic patients. METHODS: According to the random number table, 96 patients with post-stroke shoulder pain were divided into IHTAN group and warm needle moxibustion group (n＝48 in each one). Jianyu (LI15), Jianliao (TE14), Jianzhen (SI9), Binao (LI14) and Ashi points (Extra) on the affected side were selected in the two groups. For patients of the IHTAN group, internal warmth controllable acupuncture needles were inserted into the above-mentioned acupoints, and then connected to an internal heat acupuncture apparatus for stimulating the acupoints at 42 ℃， 20 min every time, once a week, for 4 weeks. For patients of the warm needle moxibustion group, the above mentioned acupoints were stimulated with filiform needles attached with an ignited moxa-stick, once every other day, for 4 weeks. If the shoulder pain disappeared or basically disappeared, it was considered to be healed, if the pain was relieved, it was considered to be effective, ot-herwise, it was considered to be ineffective. The incidence of local skin injury including burn, empyrosis, silt blue, hematoma and infection, the heart rate, respiration, blood pressure, oxyhemoglobin saturation, blood routine (hemoglobin level, white blood cell [WBC] count, platelet count), creatase and dipolymer levels were recorded or detected. Additionally, the patients' satisfaction rate about the treatment environment was recorded. RESULTS: Following the treatment, of the 45 and 47 cases in the warm needle moxibustion and IHTAN groups, 5 (11.11%) and 20 (42.55%) were cured, 26(57.78%) and 21(44.68%) experienced marked improvement, and 14 (31.11%) and 6 (12.77%) had no apparent changes in their shoulder pain severity, with the total effective rates being 68.89% and 87.23%, respectively. The curative rate and total effective rate of the IHTAN group were significantly higher than those of the warm needle moxibustion group (P<0.01，P<0.05). The incidence of skin injury of the IHTAN group was evidently lower than that of the warm needle moxibustion group (P<0.01), and the patients' therapeutic environment satisfaction rate was remarkably higher in the IHTNA group than in the warm needle moxibustion group (P<0.05). No significant differences were found between the two groups and between pre- and post-treatment in each group in the heart rate, respiration frequency, systolic and diastolic pressures, oxyhemoglobin saturation, hemoglobin content, WBC count, platelet count, and plasma dipolymer, creatine kinase, lactic dehydrogenase, and beta-hydroxybutyrate dehydrogenase levels (P>0.05). CONCLUSION: The IHTAN therapy is effective, safe and reliable in the treatment of post-stroke shoulder pain. In terms of the incidence of skin injury and the satisfaction degree of therapeutic environment, the internal heat-type acupuncture needle therapy is obviously superior to the warm needle moxibustion therapy.

[Short-term and long-term therapeutic effects of internal heat-type acupuncture needle therapy combined with acupoint injection of O3 for post-stroke shoulder pain].

OBJECTIVE: To observe the short-term and long-term therapeutic effects of internal heat-type acupuncture needle (IHTAN) therapy combined with acupoint injection of O3for post-stroke shoulder pain in apopletic patients. METHODS: Patients with post-stroke shoulder pain were divided into warm needle moxibustion ＋ acupoint injection group (29 cases), acupoint injection group (30 cases) and IHTAN＋acupoint injection group (29 cases) according to the random number table. For acupoint injection, O3 solution (3 mL, 30 µg/mL) was injected into Jianyu (LI15), Jianliao (SJ14), Jianzhen (LI9), Binao (LI14) and Ashi points (4-6 acupoints every time) on the affected side, once every other day for 4 weeks. For warm needle moxibustion, the above mentioned acupoints were stimulated with filiform needles attached with an ignited moxa-stick, once every other day for 4 weeks. For IHTAN, the internal warmth controllable acupuncture needles were inserted into the above mentioned acupoints on the affected side, and then connected to an internal heat acupuncture apparatus for stimulating the acupoints at 42 ℃， 20 min every time, once a week, for 4 weeks. The severity of shoulder pain was assessed by using visual analogue scale (VAS, 0-10 points), the upper limb joint motion function evaluated using Fugl-Meyer assessment scale (FMA, 0－66 points), and the ability of daily living activities (ADL) evaluated using Barthel index (0－100 points) at the ends of the 2nd and 4th week as well as the 6th month after the treatment. If the shoulder pain disappeared or basically disappeared, it was considered to be healed. If the pain was relieved, it was considered to be effective. Otherwise, it was considered to be ineffective. RESULTS: At the ends of the 2nd and 4th week as well as the 6th month after the treatment, the VAS scores of the IHTAN＋acupoint injection group were significantly lower than those of the warm needle moxibustion＋acupoint injection and acupoint injection groups (P<0.05), and the FMA and ADL scores were significantly higher in the IHTAN＋acupoint injection group than in the other two groups (P<0.05). No significant differences were found between the warm needle moxibustion＋acupoint injection and the acupoint injection groups in the scores of VAS, FMA and ADL (P>0.05). Of the 29, 30 and 29 cases in the warm needle moxibustion＋acupoint injection, acupoint injection and IHTNA＋acupoint injection groups, 1, 0 and 7 cases at the 2nd week, 3, 2 and 12 cases at the 4th week, 4, 2 and 15 cases at the 6th month were cured; 15, 14 and 16 cases at the 2nd week, 17, 17 and 13 cases at the 4th week, and 18, 18 and 12 cases at the 6th month experienced marked improvement; 13, 16 and 6 cases at the 2nd week, 9, 11 and 4 cases at the 4th week, 7, 10 and 2 cases at the 6th month had no apparent changes in their shoulder pain severity, with the total effective rates at the 4th week and 6th month being 68.97% and 75.86%, 63.33% and 66.60%, and 86.21% and 93.10%, respectively. CONCLUSION: The internal heat-type acupuncture needle therapy combined with O3 acupoint injection has obvious short-term and long-term therapeutic effects for post-stroke shoulder pain and is obviously superior to warm needle moxibustion＋ acupoint injection and simple acupoint injection in relieving shoulder pain and improving upper limb motion function.

An enhanced regeneration strategy to improve microbial control and prolong resin lifetime for Protein A resin in large-scale monoclonal antibody (mAb) purification.

Effective Protein A column regeneration is important in therapeutic monoclonal antibody (mAb) production for product quality and process economics. To design a robust and effective regeneration strategy, resin compatibility, microbial inactivation efficiency and cleaning effectiveness are three major considerations. Regenerating Protein A column using acidic (e.g. acetic acid) and/or caustic (e.g. NaOH) solutions is a common approach. However, it is challenging to balance between resin performance decline and adequate microbial control in choosing the right caustic solution concentration, even for resin with enhanced caustic tolerance such as MabSelect SuRe. This report introduces an enhanced regeneration strategy for MabSelect SuRe resin. The approach applies benzyl alcohol in low concentration acetic acid and NaOH (100 mM) solutions in sequential steps to regenerate MabSelect SuRe resin for reuse. Such solutions demonstrated good resin compatibility in resin functional test after extended solution incubation time, and demonstrated superior microbial control using eight test microorganisms. The cleaning effectiveness of the proposed strategy is demonstrated by carryover study, where product and impurity carryover was below detection limit. Finally, during a resin lifetime study, consistent step yields and product quality attributes were demonstrated, and no carryover was observed, up to 150 purification cycles. A viral clearance study further demonstrated that aged resin at the end of the resin lifetime had comparable viral clearance performance compared to new resin. No active virus was detected in the elution pool of the subsequent blank runs. These studies further verified the robustness of the proposed regeneration strategy for MabSelect SuRe resin.

Bioactive 3D scaffolds self-assembled from phosphorylated mimicking peptide amphiphiles to enhance osteogenesis.

Being an active scaffold in bone tissue engineering, hydrogel self-assembled from biomimetic peptide amphiphile (PA) has excellent ability to induce osteogenic differentiation and osteogenesis. Here, a multifunctional scaffold based on bone morphogenetic protein-2 (BMP-2) mimicking peptide, RGDS, and phosphoserine has been developed to enhance osteogenesis. Cell experiments in vitro displayed that the hydrogel could effectively promote rat messenchymal stem cells (rMSCs) proliferation and induce them differentiation into oesteblasts. The up-regulated RNA expression of osteogenic marker genes, like BMP-2, osteopontin (OPN), osteocalcin (OCN) and runt-related transcription factor 2 (Runx2) revealed that the scaffold could accelerate rMSCs differentiation at RNA level. Further studies on rat skull defect model demonstrated that the multifunctional scaffold exhibited excellent repair ability due to a potential synergistic effect of biomimetic peptide and phosphoserine. Histochemical/immunohistochemical staining results showed that expressions of alkaline phosphatase (ALP) and OCN was significantly up-regulated, indicating that the hydrogel could accelerate maturation of osteoblast precursors during the whole repairing process and be a promising bioactive scaffold for bone repairing.

Bioactive gel self-assembled from phosphorylate biomimetic peptide: A potential scaffold for enhanced osteogenesis.

Bone morphogenetic protein-2 biomimetic peptide (BMPBP) is a potent osteoinductive cytokine and plays a critical role during bone regeneration. Efforts to prepare hydrogels with surface modification or physical absorption of bioactive molecules do not provide sufficient bioactivity to meet the requirements of clinical application. The goal of this study was to form a three-dimensional hydrogel comprised of BMP-2 core sequence oligopeptide, phosphoserine, a synthetic cell adhesion peptide (RGDS), and polyaspartic acid to synergistically promote osteogenesis. Experiments performed in vitro revealed that the peptide gel was conducive to adhesion and proliferation of rat marrow mesenchymal stem cells (rMSCs). In addition, RT-PCR analysis indicated that rMSCs allowed better expression of osteogenesis-related genes such as BMP-2, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Use of the rat cranial bone defects model with micro-CT 3D reconstruction showed that bone regeneration patterns occurred from one side edge toward the center of the area implanted with the prepared biomimetic peptide hydrogels, demonstrating significantly accelerated bone regeneration. This work will provide a basis to explore the further application potential of this bioactive scaffold.