Effects of Patient-Controlled Transcutaneous Electrical Acupoint Stimulation on Cancer Induced Bone Pain Relief in Patients with Non-Small Cell Lung Cancer: Study Protocol for a Randomized Controlled Trial.

Background: Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC). Methods/Design: This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight. Discussion: PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP. Trial Registration: ClinicalTrials.gov NCT05730972, registered February 16, 2023.

Epsilon-poly-l-lysine microneedle patch loaded with amorphous doxycycline nanoparticles for synergistic treatment of skin infection.

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.

Lancao decoction alleviates cognitive dysfunction: A new therapeutic drug and its therapeutic mechanism.

BACKGROUND: Cognitive dysfunction (CD) is a neurodegenerative disease characterized primarily by the decline of learning and memory abilities. The physiological and pathological mechanisms of CD are very complex, which is mainly related to normal function of the hippocampus. Lancao decoction (LC) is a Chinese medicine formula, which has been used to treat neurodegenerative disorders. However, the potential of LC for the treatment of CD, as well as its underlying mechanisms, is unclear. PURPOSE: In the study, we aimed to reveal the functional and neuronal mechanisms of LC's treatments for CD in scopolamine-induced mice. METHODS: Gas chromatography (GC) was used to determine the stability of LC's extraction. CD model was established by the chronic induction of scopolamine (Scop, 1 mg/kg/day) for 1 week. Behavioral tests including morris water maze (MWM) and y-maze were used to evaluate learning and memory abilities of mice after LC's treatments. Immunofluorescence was used to detected the expressions of cFOS, Brdu and Ki67 after LC's treatments. Pharmacological blockade experiments explored the role of α-Amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in LC's treatments for CD and its relationships with regeneration, activities and differentiation of neurons. RESULTS: The results showed that LC was capable of improving spatial learning and memory and spontaneous alternating abilities in Scop-induced mice, which was similar to donepezil. LC could increase the number of cFOS positive cells, which was used as a marker of neuronal activity to upregulate by neuronal activities in hippocampus, but donepezil did not. Moreover, LC could strengthen neurogenesis and neuro-differentiation by increasing the number of Brdu and Ki67 positive cells in hippocampal dentate gyrus (DG), meanwhile, donepezil could only enhance the number of Ki67 positive cells. Transient inhibition of AMPAR by NBQX blunted the function of LC's treatment for CD and inhibited the enhanced effect of LC on Scop-induced hippocampal neuronal excitability and neurogenesis in mice. CONCLUSION: To sum up, our study demonstrated that LC had the function of treating CD by enhancing content of acetylcholine (ACh) to activate AMPAR, which further up-regulated neurogenesis and neuronal differentiation to strengthen neuroactivities in hippocampus.

Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study.

BACKGROUND: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. METHODS: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. CONCLUSIONS: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.

ATP-adenosine axis regulation combined with microneedle assisted photoimmunotherapy to boost the immunotherapy efficiency.

Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy. Upon insertion into the tumor site, IR780 induces ICD modalities with the release of damage-associated molecular patterns from endogenous tissues, which activates the antitumor immune cycle. Simultaneously, POM-1 promotes the liberation of immunostimulatory ATP and lowers the level of immunosuppressive extracellular adenosine, which supported immune control of tumors via recruiting CD39-expressing immune cells. In vivo antitumor studies prove that this platform can effectively eliminate mice melanoma (tumor growth inhibitory rate of 96.5%) and colorectal adenocarcinoma (tumor growth inhibitory rate of 93.5%). Our results shed light on the immunological aspects of combinatorial phototherapy and ATP-adenosine regulation, which will broaden the scope of synergistic antitumor immunotherapy.

Application of Hospital-Community-Family "Trinity" Remote Rehabilitation Guidance Based on Internet + WeChat Platform in Patients with Stroke After Discharge.

Objective: To investigate the impact of an Internet + WeChat platform-based "trinity" remote rehabilitation model involving the hospital, community, and family on stroke patient rehabilitation nursing. Methods: 159 patients with stroke who were discharged from Beijing Luhe Hospital of Capital Medical University from January 1, 2018, to December 31, 2019, were selected and divided into a control group (79 cases) and an experimental group (80 cases) by the random drawing method. The control group was given routine nursing, and the experimental group was given remote rehabilitation nursing intervention by using the WeChat network platform based on the control group. Limb function [Fugl-Meyer Assessment Scale (FMA)] and activities of daily living [Modified Barthel Index (MBI)] were evaluated at enrollment and at the end of 3 months, 6 months and 12 months in both groups. The compliance and satisfaction surveys in the two groups were evaluated after 6 months and 12 months of intervention. Results: (1) Before the intervention, there was no statistical significance in FMA score between the two groups (t = 0.798, P > .05). After 3 months, 6 months and 12 months of intervention, the FMA score in the two groups was increased compared with that before intervention (t = 2.463, P < .05), and the FMA scores in the experimental group at the above time points were higher than those in the control group (ts = 7.057, 14.285, Ps < .05). (2) There was no statistical difference in MBI scores between the two groups before intervention (t = 0.798, P > .05). After 3 months, 6 months, and 12 months of intervention, the MBI score in the two groups was increased compared with that before intervention (t = 0.232, P < .05), and MBI scores in the experimental group at the above time points were higher compared to the control group (ts = 4.959, 8.842, 8.131, Ps < .05). (3) The compliance scores in the experimental group were higher than those in the control group after 6 months and 12 months of intervention (ts = 4.959, 8.842, 8.131, Ps < .05). (4) The satisfaction survey scores in the experimental group after 6 months and 12 months of intervention were higher than those in the control group (ts = 2.120 ~ 14.554, Ps < .05). Conclusion: The Hospital-community-family "trinity" stroke rehabilitation model on the WeChat network platform holds significant importance. Enhancing limb function and daily living for stroke patients improves their quality of life and lessens reliance on caregivers. This positively impacts both survivors' well-being and healthcare resources. Increased patient satisfaction and compliance suggest a potential revolution in post-stroke care, favoring a more patient-centered approach. Overall, this model has transformative potential for stroke treatment, offering holistic and patient-focused strategies. Its success promises better rehabilitation outcomes, patient satisfaction, and cost reduction, while paving the way for innovative research in stroke treatment and rehabilitation.

The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.

Site-Specifically Launched Microneedles for the Combined Treatment of Psoriasis-Diabetic Comorbidity.

Psoriasis and diabetes are both common comorbidities for each other, where inflammation and insulin resistance act in a vicious cycle, driving the progression of disease through the activation of the NF-κB signaling pathway. Therefore, disrupting the linkage between inflammation and insulin resistance by inhibiting the NF-κB pathway presents a promising therapeutic strategy for addressing psoriasis-diabetic comorbidity. Herein, an open-loop therapy was developed by integrating microneedle-mediated short- and long-range missiles to target psoriasis and diabetes, respectively. The short-range missile (curcumin nanoparticle) could be stationed in the psoriatic skin for topical and prolonged antipsoriasis therapy, while the long-range missile (metformin) is capable of penetrating transdermal barriers to induce a systemic hypoglycemic effect. More attractively, the short- and long-range missiles could join hands to inhibit the NF-κB signaling pathway and diminish inflammation, effectively disrupting the crosstalk between inflammation and insulin resistance. Pharmacodynamic studies showed that this microneedle-mediated combination, possessing dual anti-inflammatory and antihyperglycemic properties, proves to be highly efficacious in alleviating typical symptoms and inflammatory response in both nondiabetic and diabetic mice with imiquimod (IMQ)-induced psoriasis models. Hence, the microneedle-mediated open-loop therapy shows great potential in the management of psoriasis-diabetes comorbidity.

[Cloning and expression analysis of U6 promoters in Panax quinquefolius].

The U6 promoter is an important element driving sgRNA transcription in the CRISPR/Cas9 system. Seven PqU6 promo-ter sequences were cloned from the gDNA of Panax quinquefolium, and the transcriptional activation ability of the seven promoters was studied. In this study, seven PqU6 promoter sequences with a length of about 1 300 bp were cloned from the adventitious roots of P. quinquefolium cultivated for 5 weeks. Bioinformatics tools were used to analyze the sequence characteristics of PqU6 promoters, and the fusion expression vectors of GUS gene driven by PqU6-P were constructed. Tobacco leaves were transformed by Agrobacterium tumefaciens-mediated method for activity detection. The seven PqU6 promoters were truncated from the 5'-end to reach 283, 287, 279, 289, 295, 289, and 283 bp, respectively. The vectors for detection of promoter activity were constructed with GUS as a reported gene and used to transform P. quinquefolium callus and tobacco leaves. The results showed that seven PqU6 promoter sequences(PqU6-1P to PqU6-7P) were cloned from the gDNA of P. quinquefolium, with the length ranged from 1 246 bp to 1 308 bp. Sequence comparison results showed that the seven PqU6 promoter sequences and the AtU6-P promoter all had USE and TATA boxes, which are essential elements affecting the transcriptional activity of the U6 promoter. The results of GUS staining and enzyme activity test showed that all the seven PqU6 promoters had transcriptional activity. The PqU6-7P with a length of 1 269 bp had the highest transcriptional activity, 1.31 times that of the positive control P-35S. When the seven PqU6 promoters were truncated from the 5'-end(PqU6-1PA to PqU6-7PA), their transcriptional activities were different in tobacco leaves and P. quinquefolium callus. The transcriptional activity of PqU6-7PA promoter(283 bp) was 1.59 times that of AtU6-P promoter(292 bp) when the recipient material was P. quinquefolium callus. The findings provide more ideal endogenous U6 promoters for CRISPR/Cas9 technology in ginseng and other medicinal plants.

Matured compost amendment improves compost nutrient content by changing the bacterial community during the composting of Chinese herb residues.

Composting is a sustainable strategy to deal with organic waste. Our research aimed to study the influence of an amendment of 10% matured compost (MC) during Chinese herb residue (CHR) compost. Here, a 60-day CHR compost was performed, and MC application was able to reduce the nitrogen loss and enhance the humic acid accumulation during the composting as compared with the non-inoculated control (NC), by 25 and 19%, respectively. Furthermore, the matured compost amendment improved the diversity of the bacterial community, increased the complexity of the co-occurrence network, and changed the keystone and module hub bacteria during composting. The increased abundance levels of Thermopolyspora, Thermobispora, and Thermosporomyces, which were significantly higher in MC than in NC, may contribute to the degradation of cellulose and the formation of humic acid. Overall, this study extends our understanding of the effects of matured compost reflux on compost quality and the bacterial community.

Efficacy of electroacupuncture in the treatment of peripheral neuropathy caused by Utidelone: Study protocol for a randomized controlled trial.

Introduction: Utidelone (UTD1) is a new chemotherapeutic drug for recurrent or metastatic breast cancer. However, it usually leads to severe peripheral neuropathy (PN) and causes numbness of the hands and feet and significant pain in patients' life. Electroacupuncture (EA) is considered beneficial in improving PN and relieving numbness of the hands and feet. This trial aims to evaluate the therapeutic effect of EA on PN caused by UTD1 in patients with advanced breast cancer. Methods and analysis: This study is a prospective randomized controlled trial. A total of 70 patients with PN caused by UTD1 will be randomly assigned to the EA treatment group and the control group in a ratio of 1:1. The patients in the EA treatment group will receive 2 Hz EA three times a week for 4 weeks. The patients in the control group will take mecobalamin (MeCbl) tablets orally, one tablet each, three times a day for 4 weeks. The main outcome measures will be the evaluation scale of peripheral neurotoxicity of chemotherapeutic drugs according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN 20-item (EORTC QLQ-CIPN20) and the peripheral neurotoxicity assessment rating according to NCI CTCAE version 5.0. Secondary outcomes will be the quality of life scale according to the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). The results will be evaluated at baseline, post-treatment phase, and follow-up. All major analyses will be based on the intention-to-treat principle. Ethics and dissemination: This protocol was approved by the Medical Ethics Committee of Zhejiang Cancer Hospital on 26 July 2022. The license number is IRB-2022-425. This study will provide clinical efficacy data on EA in the treatment of PN caused by UTD1 and will help to prove whether EA is an effective and safe therapy. The study results will be shared with healthcare professionals through the publication of manuscripts and conference reports. Trial registration number: ChiCTR2200062741.

Core Constituents of Caragana sinica Root for Rheumatoid Arthritis Treatment and the Potential Mechanism.

PURPOSE: As a traditional herb product, the root of Caragana sinica (Buc'hoz) Rehder (Chinese name: Jin Quegen [JQG]) has been widely used in folk medicines for rheumatoid arthritis (RA) treatment. However, which herbal constituents exert a core pharmacological role in RA treatment remains a great challenge due to the multiple phytochemical constituents, targets, and pathways. In this work, we aimed to use a new strategy to explore the core herbal constituents and potential mechanisms of JQG against RA for the first time. METHODS: A successively partitioned extract of JQG, bioactive partition screening in vitro and in vivo, qualitative analysis, bioinformatic analysis, molecular docking, and mechanism validation were used in this study. The partitioned extract was used to obtain the bioactive partition, while in vitro anti-inflammatory effects and in vivo anti-arthritis effects in adjuvant-induced arthritis (AIA) rats were applied to screen the bioactive partition with the best efficacy. Qualitative analysis was used to identify bioactive constituents. Bioinformatic analysis was used to explore the potential mechanism for RA treatment. Molecular docking and immunofluorescence were used to validate the underlying mechanism. RESULTS: After successively partitioning extract and bioactive partition screening, ethyl acetate extract (EAE) yielded the best anti-inflammatory effects in vitro and in vivo among JQG extracts. By ultra-performance liquid chromatography (UPLC) coupled with Orbitrap mass spectrometry, a total of 58 constituents were identified in EAE, and 17 constituents were regarded as the core constituents based on their oral bioavailability and drug-like properties. The nuclear factor kappa B (NF-κB) signal pathway was screened as the core pathway of core constituents for RA treatment based on bioinformatic analysis, and the core constituents showed good ligand-receptor binding activity to NF-κB P65. In vitro study demonstrated that EAE could significantly reduce NF-κB P65 transfer from the cytoplasm to the nucleus. CONCLUSION: Our study suggested that the therapeutic efficacy of JQG for RA treatment could be derived from negative regulation of the NF-κB pathway, and EAE of JQG could represent a promising herb product for RA treatment that deserves further development.

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study.

OBJECTIVE: To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL). METHODS: This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded. RESULTS: The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group. CONCLUSIONS: TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).

Efficacy of electro-acupuncture in postpartum with diastasis recti abdominis: A randomized controlled clinical trial.

Background: Electro-acupuncture (EA) has promising effects on diastasis rectus abdominis (DRA), defined as a separation of the two muscle bellies of rectus abdominis. To study, there is scant knowledge or scarce high-quality evidence. Objective: We aimed to evaluate the long-term efficacy and safety of EA in treating DRA during postpartum. It was assumed that the improvement of DRA was more obvious in the EA group than in the control group. Design: Randomized, controlled, blinded trial (Clinical Trial Registration: ChiCTR2100041891). Setting: Hangzhou Hospital of Traditional Chinese Medicine in China. Participants: Females aged 20-45 years without a past medical history of pathological rectus abdominal dissection were recruited from DRA inclusion criteria from 42 days to 1 year postpartum. Intervention: 110 participants were randomly assigned in a 1:1 ratio to a control group with no EA intervention (n = 55), and EA group (n = 55). The EA group received ten sessions of EA combined with physical exercise or only physical exercise for 2 weeks with a 26-week follow-up. Measurements: Outcomes were assessed at baseline, week 2, and week 26. The primary outcome was the change of the inter recti distance (IRD) and electromyographic evaluation of the pelvic floor. Secondary outcomes included elasticity of linea alba (LA), paraumbilical subcutaneous adipose tissue (SAT) measurement, body mass index (BMI), percentage body fat (F%), dyspepsia symptoms, menstrual symptoms, quality of life (QoL), pain performance of patients with lower back pain, postnatal depression symptoms (PDS), postpartum self-image, and DRA-related symptom assessment including urine leakage, frequency, and urgency, constipation, sexual dysfunction, and chronic pelvic pain. Results: A total of 110 maternal (55 in each group) were recruited. The mean difference in IRD from baseline to week 2 and week 26 in all states of the two groups were reduced compared with those before treatment, with statistical significance (P < 0.05). The mean of IRD at the horizontal line of the umbilicus in the end-expiratory state was smaller in the EA group than in the control group, but the difference was not statistically significant (P > 0.05) at week 2. The mean of IRD at the horizontal line of the umbilicus in head-up and flexed knee state was smaller in the EA group than in the control group, and the difference was statistically significant (P < 0.05) at week 26. Five (9.1%) and thirteen (23.64%) adverse events were reported in EA and control groups, respectively. No serious adverse events were reported. Limitation: The frequency intensity of EA parameters was selected between 4 and 6 because of individual tolerance differences. Conclusion: EA is an effective approach to improve IRD, electromyographic evaluation of the pelvic floor, BMI, the elasticity of LA, paraumbilical SAT, and symptoms of DRA, with durable effects at 26 weeks. Primary funding source: The Construction Fund of Medical Key Disciplines of Hangzhou (Project Number: OO20200097), Hangzhou Medical and Health Science and Technology Project No. A20200483, and Zhejiang Traditional Chinese Medicine Science and Technology Plan Project (Project Number: 2021ZQ065). Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR2100041891.

Compact 100GBaud driverless thin-film lithium niobate modulator on a silicon substrate.

Electro-optic (EO) modulators with a high modulation bandwidth are indispensable parts of an optical interconnect system. A key requirement for an energy-efficient EO modulator is the low drive voltage, which can be provided using a standard complementary metal oxide semiconductor circuity without an amplifying driver. Thin-film lithium niobate has emerged as a new promising platform, and shown its capable of achieving driverless and high-speed EO modulators. In this paper, we report a compact high-performance modulator based on the thin-film lithium niobate platform on a silicon substrate. The periodic capacitively loaded travelling-wave electrode is employed to achieve a large modulation bandwidth and a low drive voltage, which can support a driverless single-lane 100Gbaud operation. The folded modulation section design also helps to reduce the device length by almost two thirds. The fabricated device represents a large EO bandwidth of 45GHz with a half-wave voltage of 0.7V. The driverless transmission of a 100Gbaud 4-level pulse amplitude modulation signal is demonstrated with a power consumption of 4.49fj/bit and a bit-error rate below the KP4 forward-error correction threshold of 2.4×10-4.

Sasanquasaponin inhibited epithelial to mesenchymal transition in prostate cancer by regulating the PI3K/Akt/mTOR and Smad pathways.

CONTEXT: Sasanquasaponin (SQS) is a commonly used traditional Chinese medicine proved to have a wide range of pharmacological functions. OBJECTIVE: The objective of this study is to explore the effect and underlying mechanism of SQS in the treatment of prostate cancer (PC). MATERIALS AND METHODS: PC cell lines (22Rv1 and PC-3) were treated with SQS (0, 0.5, 1, 2, and 4 µM) for 12 or 24 h. The viability of cells was evaluated, while the mRNA and protein levels of epithelial to mesenchymal transition (EMT)-related genes in PC cell lines were measured (Groups: Control, TGF-ß1, TNF-α, TGF-ß1 + TNF-α, and TGF-ß1 + TNF-α + SQS). The migration and invasion abilities of PC cell lines were evaluated (Groups: Control, SQS). Finally, the antitumour effect of SQS (25, 50,100, and 200 mg/kg) in BALB/c nude mice (6 weeks, 18-20 g) was evaluated (Groups: Control, Vehicle, 25, 50,100, and 200 mg/kg SQS). The study duration was 1 month. RESULTS: SQS inhibited the viability and the number of colonies of 22Rv1 or PC-3 cells. The IC50 of SQS of 12 and 24 h in these two cells was 3.25, 1.82, 4.76, and 4.70 µM, respectively. SQS inhibited the adhesion, migration, and invasion of PC cells. It also inhibited the expression of EMT-related markers of PC cells. The PI3K/Akt/mTOR and Smad2/3 signalling pathways were activated in the process of EMT, and SQS could significantly reduce the activation of the PI3K/Akt/mTOR and Smad2/3 pathways. Finally, SQS inhibited the growth of xenograft tumours in vivo. CONCLUSIONS: SQS inhibited EMT in PC by regulating the PI3K/Akt/mTOR and Smad pathways.

The Analysis of Causality and Risk Spillover between Crude Oil and China's Agricultural Futures.

This paper aims to apply the time-varying Granger causality test (TVGC) and the DY Spillover Index (Diebold and Yilmaz, 2012) to measure the Granger causality and dynamic risk spillover effects of the international crude oil futures market on China's agricultural commodity futures market from the perspectives of return and volatility spillovers. Empirical evidence relating to the TVGC test suggests the existence of unidirectional Granger causality between crude oil futures and agricultural product futures. This relationship shows a strong time-varying property, in particular for sudden or extreme events such as financial crises and natural disasters. On the other hand, the volatility spillover in crude oil and agricultural product futures markets responds asymmetrically and bidirectionally according to the result of the DY Spillover index, and the periodicity of total volatility spillover correlates closely with the occurrence of global economic events, which indicates that the spillover effect between crude oil and agricultural commodity futures markets will be exacerbated in turbulent financial and economic times. Such findings are expected to help in formulating policy recommendations, portfolio design, and risk-management decisions.

Efficacy of electroacupuncture with different frequencies in the treatment of chemotherapy-induced peripheral neuropathy: A study protocol for a randomized controlled trial.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication in patients with cancer during chemotherapy. It mainly leads to severe numbness of the hands and feet and causes great pain in patients. Electroacupuncture (EA) is considered to be beneficial in improving peripheral neuropathy and relieving numbness of the hands and feet. This trial aims to evaluate the therapeutic effect of different frequencies of EA on CIPN in patients with cancer. Methods and analysis: This study is a randomized controlled trial. In total, 160 eligible CIPN patients are randomly assigned to the 2 Hz EA group, 100 Hz EA group, 2/100 Hz EA group, and control group in the ratio of 1:1:1:1. All patients in the EA treatment groups receive treatment with EA three times a week for 4 weeks and following up for 4 weeks. The patients in the control group are given Mecobalamin (MeCbl) tablets orally, one tablet at a time, three times a day, for 4 weeks, and following up for 4 weeks. The primary outcome measures are the participant neurotoxicity questionnaire (PNQ) and the peripheral neurotoxicity assessment rating (NCI CTCAE V5.0). Secondary outcomes are the quality of life scale (EORTC QLQ-C30) and the measurement of peripheral nerve conduction velocity (NCV). The results are evaluated at baseline, post-treatment phase, and following up for 4 weeks. All major analyses are based on the intention to treat principle. Ethics/dissemination: This protocol was approved by the Medical Ethics Committee of the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) on 7 December 2021. The license number is IRB-2021-458. This study provides clinical efficacy data of different frequencies of EA in the treatment of CIPN. The results help to prove whether EA is an effective therapy for CIPN and optimize the frequency of EA for CIPN. The results of this study are shared with health care professionals, the public, and relevant organizations through the publication of manuscripts and conference reports. Trial registration number: ChiCTR2100054458.

Upconversion Nanostructures Applied in Theranostic Systems.

Upconversion (UC) nanostructures, which can upconvert near-infrared (NIR) light with low energy to visible or UV light with higher energy, are investigated for theranostic applications. The surface of lanthanide (Ln)-doped UC nanostructures can be modified with different functional groups and bioconjugated with biomolecules for therapeutic systems. On the other hand, organic molecular-based UC nanostructures, by using the triplet-triplet annihilation (TTA) UC mechanism, have high UC quantum yields and do not require high excitation power. In this review, the major UC mechanisms in different nanostructures have been introduced, including the Ln-doped UC mechanism and the TTA UC mechanism. The design and fabrication of Ln-doped UC nanostructures and TTA UC-based UC nanostructures for theranostic applications have been reviewed and discussed. In addition, the current progress in the application of UC nanostructures for diagnosis and therapy has been summarized, including tumor-targeted bioimaging and chemotherapy, image-guided diagnosis and phototherapy, NIR-triggered controlled drug releasing and bioimaging. We also provide insight into the development of emerging UC nanostructures in the field of theranostics.

[Cloning and expression analysis of 8 bHLH transcription factors in Panax quinquefolius].

A total of 8 bHLH transcription factors were cloned from Panax quinquefolius and the response of them to methyl jasmonate(MeJA) was studied.To be specific, based on the preliminary transcriptome screening, 8 bHLH transcription factors were cloned with seedlings which had been cultured for 3 weeks.The content of ginsenosides Rg_1, Re, and Rb_1, and total saponins in the adventitious roots of P.quinquefolius was determined at different time of MeJA treatment by high performance liquid chromatography(HPLC) and spectrophotometry.Real-time quantitative polymerase chain reaction(PCR) was used to detect the relative expression of 8 transcription factors after MeJA treatment.The correlation between the relative expression of the 8 transcription factors and the saponin content after MeJA treatment was checked by Pearson's correlation analysis.The results showed that the PCR products(Pq-bHLH21-Pq-bHLH28) of the 8 bHLH transcription factors were 762-2 013 bp in length.They were submitted to NCBI to obtain the Genbank access numbers.The proteins yielded from Pq-bHLH21-Pq-bHLH28 showed amino acid sequence identity of 24.90%, and each amino acid sequence had the bHLH(Basic Helix-loop-helix) conserved domain and belonged to the bHLH family.The 5 amino acid sequences of Pq-bHLH22 and Pq-bHLH24-Pq-bHLH27 contained the bHLH-MYC N domain, which belonged to the MYC transcription factors.Pq-bHLH21-Pq-bHLH28 responded to MeJA within 48 h of treatment.At 72 h, the expression of Pq-bHLH24 reached 106.53 folds the highest in the treatment group.Pq-bHLH25, Pq-bHLH27, and Pq-bHLH28 showed synergic expression.Pq-bHLH21 may re-gulate the biosynthetic pathway of ginsenoside Rb_1, while Pq-bHLH22, Pq-bHLH25, and Pq-bHLH28 were in significantly positive correlation with the biosynthetic pathway of ginsenoside Re.The result lays a foundation for further verifying the regulation of ginsenoside biosynthesis by bHLH transcription factors.