6-O-angeloylplenolin inhibits osteoclastogenesis in vitro via suppressing c-Src/NF-κB/NFATc1 pathways and ameliorates bone resorption in collagen-induced arthritis mouse model.

One of the effective therapeutic strategies to treat rheumatoid arthritis (RA)-related bone resorption is to target excessive activation of osteoclasts. We discovered that 6-O-angeloylplenolin (6-OAP), a pseudoguaianolide from Euphorbia thymifolia Linn widely used for the treatment of RA in traditional Chinese medicine, could inhibit RANKL-induced osteoclastogenesis and bone resorption in both RAW264.7 cells and BMMs from 1 µM and protect a collagen-induced arthritis (CIA) mouse model from bone destruction in vivo. The severity of arthritis and bone erosion observed in paw joints and the femurs of the CIA model were attenuated by 6-OAP administered at both dosages (1 or 5 mg/kg, i.g.). BMD, Tb.N and BV/TV were also improved by 6-OAP treatment. Histological analysis and TRAP staining of femurs further confirmed the protective effects of 6-OAP on bone erosion, which is mainly due to reduced osteoclasts. Molecular docking indicated that c-Src might be a target of 6-OAP and phosphorylation of c-Src was suppressed by 6-OAP treatment. CETSA and SPR assay further confirmed the potential interaction between 6-OAP and c-Src. Three signaling molecules downstream of c-Src that are vital to the differentiation and function of osteoclasts, NF-κB, c-Fos and NFATc1, were also suppressed by 6-OAP in vitro. In summary, the results demonstrated that the function of c-Src was disrupted by 6-OAP, which led to the suppression of downstream signaling vital to osteoclast differentiation and function. In conclusion, 6-OAP has the potential to be further developed for the treatment of RA-related bone erosion.

Vitamin D3 promotes fish oocyte development by directly regulating gonadal steroid hormone synthesis†.

Vitamin D receptors and vitamin D3-metabolizing enzymes have been found to be highly expressed in the ovaries and spermatophores of fish. However, the role of vitamin D3 on fish gonadal development has rarely been reported. In this study, 2-month-old female zebrafish were fed with different concentrations of vitamin D3 diets (0, 700, 1400, and 11 200 IU/kg) to investigate the effects of vitamin D3 on ovarian development. The diet with 0 IU/kg vitamin D3 resulted in elevated interstitial spaces, follicular atresia, and reproductive toxicity in zebrafish ovaries. Supplementation with 700 and 1400 IU/kg of vitamin D3 significantly increased the oocyte maturation rate; upregulated ovarian gonadal steroid hormone synthesis capacity; and elevated plasma estradiol, testosterone, and ovarian vitellogenin levels. Furthermore, the current study identified a vitamin D response element in the cyp19a1a promoter and demonstrated that 1.25(OH)2D3-vitamin D response directly activated cyp19a1a production through activating the vitamin D response element. In conclusion, this study shows that an appropriate concentration of vitamin D3 can promote zebrafish ovarian development and affect vitellogenin synthesis through the vdr/cyp19a1a/er/vtg gene axis.

Effect of 10.6-µm CO2 laser moxibustion on the fastest 15-m walking time in patients with knee osteoarthritis: a double-blind, sham-controlled, multi-site randomized trial.

BACKGROUND: In this study, we investigated the impact of 10.6-µm CO2 laser moxibustion (LM) on the fastest 15-m walking time in individuals suffering from knee osteoarthritis (KOA). METHODS: A total of 392 individuals diagnosed with KOA and meeting the specified eligibility criteria were assigned randomly into two groups: the LM treatment group and the sham LM control group (ratio 1:1). Both groups received either LM therapy or simulated LM therapy to address the affected area of the knee joint. This treatment was administered three times a week for a duration of 4 weeks. RESULTS: In the LM group, the fastest 15-m walking times at both Week 4 and Week 12 were significantly reduced compared to the times before treatment (all P < 0.05). However, in the sham LM group, there were no notable differences in the fastest 15-m walking times after treatment (all P > 0.05). Moreover, the LM group exhibited shorter 15-m walking times than the sham LM group at both Week 4 and Week 12 (all P < 0.05). CONCLUSION: The use of CO2 LM can lead to a substantial enhancement in the fastest 15-m walking time of individuals suffering from KOA, and its therapeutic impact can last for a minimum of 8 weeks post-treatment. The fastest 15-m walking time serves as an indicator of alterations in the walking capacity of patients with KOA.

Self-assembled nano-photosensitizer for targeted, activatable, and biosafe cancer phototheranostics.

Cancer treatment currently still faces crucial challenges in therapeutic effectiveness, precision, and complexity. Photodynamic therapy (PDT) as a non-invasive tactic has earned widespread popularity for its excellent therapeutic output, flexibility, and restrained toxicity. Nonetheless, drawbacks, including low efficiency, poor cancer specificity, and limited therapeutic depth, remain considerable during the cancer treatment. Although great effort has been made to improve the performance, the overall efficiency and biosafety are still ambiguous and unable to meet urgent clinical needs. Herein, this study integrates merits from previous PDT strategies and develops a cancer-targeting, activatable, biosafe photosensitizer. Owing to excellent self-assembly ability, this photosensitizer can be conveniently prepared as multifunctional nano-photosensitizers, namely MBNPs, and applied to in vivo cancer phototheranostics in "all-in-one" mode. This study successfully verifies the mechanism of MBNPs, then deploys them to cell-based and in vivo cancer PDT. Based on the unique cancer microenvironment, MBNPs achieve precise distribution, accumulation, and activation towards the tumor, releasing methylene blue as a potent photosensitizer for phototherapy. The PDT outcome demonstrates MBNPs' superior cancer specificity, remarkable PDT efficacy, and negligible toxicity. Meanwhile, in vivo NIR fluorescence and photoacoustic imaging have been utilized to guide the PDT treatment synergistically. Additionally, the biosafety of the MBNPs-based PDT treatment is ensured, thus providing potential for future clinical studies.

Acupuncture for cancer-related conditions: An overview of systematic reviews.

BACKGROUND: Acupuncture is commonly used for cancer-related conditions worldwide, and evidence is increasing year on year. There is a need to summarize the evidence of acupuncture for cancer-related conditions comprehensively and critically. OBJECTIVE: To evaluate and summarize the systematic reviews (SRs) that assess the effects and safety of acupuncture for cancer-related conditions, and to inform clinical practice and future studies. METHODS: A comprehensive search was conducted on Pubmed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Sinomed, and Wanfang from their inception to October 16, 2021. SRs of randomized controlled trials (RCTs) on acupuncture for cancer-related conditions were to be included. Two reviewers screened the eligible articles, and four reviewers in pair extracted data and assessed the methodological quality/risk of bias of all included reviews by AMSTAR 2 and ROBIS tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a summary of meta-analysis or narrative description. RESULTS: Fifty-one SRs of RCTs on acupuncture for cancer-related conditions were included and synthesized. The methodological quality of SRs included 1 "high", 5 "low" and 45 "very low" by AMSTAR 2. Sixteen SRs assessed as low risk of bias (31.37%), and 35 SRs had high risk of bias (68.63%) by ROBIS. Acupuncture showed effective on systemic conditions in relation to different cancers, including cancer-related pain (17 SRs, 80 RCTs), fatigue (7 SRs, 18 RCTs), insomnia (4 SRs, 10 RCTs), quality of life (2 SRs, 15 RCTs); conditions in relation to chemo-radiotherapy, including nausea and vomiting (3 SRs, 36 RCTs) and bone marrow suppression (2 SRs, 21 RCTs); and conditions in relation to specific cancers, including breast cancer-related menopause (3 SRs, 6 RCTs), hot flashes (12 SRs, 13 RCTs), arthralgia (5 SRs, 10 RCTs), and nasopharyngeal cancer-related dysphagia (1 SRs, 7 RCTs). Acupuncture appeared to have benefit for patients with lymphoedema (3 SRs, 3 RCTs), gastrointestinal function (5 SRs, 27 RCTs), and xerostomia (4 SRs, 7 RCTs). Limited evidence showed inconsistent results on acupuncture for chemotherapy-induced peripheral neuropathy (3 SRs, 6 RCTs), depression and anxiety (3 SRs, 9 RCTs). Acupuncture was regarded as a safe therapy for cancer patients as no severe adverse events related were reported. CONCLUSION: Evidence from SRs showed that acupuncture is beneficial to cancer survivors with cancer-related pain, fatigue, insomnia, improved quality of life, nausea and vomiting, bone marrow suppression, menopausal symptoms, arthralgia, and dysphagia, and may also be potential for lymphoedema, gastrointestinal function, and xerostomia. For neuropathy, depression and anxiety, acupuncture should be used as an option based on individual conditions. Acupuncture is relatively safe without serious adverse events. More well-designed clinical trials of acupuncture are recommended on cancer-related depression and anxiety, arthralgia, xerostomia, gastrointestinal dysfunction and dysphagia.

Low level light therapy/photobiomodulation for diabetic peripheral neuropathy: protocol of a systematic review and meta-analysis.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes that strongly impact the patients' quality of life and working ability. Evidence indicated that low level light therapy (LLLT)/photobiomodulation might be effective for neuropathy. However, the effect of LLLT for DPN is not clear. The objective of this systematic review and meta-analysis is to determine the effects and safety of LLLT/photobiomodulation for DPN, in comparison with other methods such as sham light, no treatment, other active treatment and LLLT as an additional treatment compared with another treatment alone. METHODS AND ANALYSIS: We will search eight databases from their inception to the date before the review submission. Randomised controlled trials (RCTs) will be included. Two reviewers will independently extract data using a structured data extraction method and assess the risk of bias in the included studies. Data will be synthesised using standardised mean difference or risk ratio with 95% CIs for continuous and dichotomous data, respectively. The primary outcome will be change in pain and secondary outcomes will include global symptom improvement, functional impairment and disability, impairment of sensation, quality of life, nerve conduction, and adverse events. Sensitivity and subgroup analysis will be employed to explore the influence of possible clinical and methodological characteristics. Publication bias will be assessed using funnel plot. We will conduct meta-analysis with RevMan V.5.4 and evaluate quality of the evidence using GRADE approach. ETHICS AND DISSEMINATION: This study does not require ethics approval. Our findings will be disseminated in the peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42021276056.

Spectrum-Effect Relationship Analysis of Bioactive Compounds in Zanthoxylum nitidum (Roxb.) DC. by Ultra-High Performance Liquid Chromatography Mass Spectrometry Coupled With Comprehensive Filtering Approaches.

Zanthoxylum nitidum (Roxb.) DC. (ZN), with strong effects of anti-inflammation and antioxidant activities is treated as a core herb in traditional Chinese medicine (TCM) preparation for treating stomachache, toothache, and rheumatoid arthritis. However, the active ingredients of ZN are not fully clarified due to its chemical complexity. In the present study, a double spectrum-effect analysis strategy was developed and applied to explore the bioactive components in herbs, and ZN was used as an example. Here, the chemical components in ZN were rapidly and comprehensively profiled based on the mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension approaches. Furthermore, the fingerprints of 20 batches of ZN samples were analyzed by high-performance liquid chromatography, and the anti-inflammatory and antioxidant activities of the 20 batches of ZN samples were studied. Finally, the partial least squares regression (PLSR), gray relational analysis models, and Spearman's rank correlation coefficient (SRCC) were applied to discover the bioactive compounds in ZN. As a result, a total of 48 compounds were identified or tentatively characterized in ZN, including 35 alkaloids, seven coumarins, three phenolic acids, two flavonoids, and one lignan. The results achieved by three prediction models indicated that peaks 4, 12, and 17 were the potential anti-inflammatory compounds in ZN, whereas peaks 3, 5, 7, 12, and 13 were involved in the antioxidant activity. Among them, peaks 4, 5, 7, and 12 were identified as nitidine, chelerythrine, hesperidin, and oxynitidine by comparison with the standards and other references. The data in the current study achieved by double spectrum-effect analysis strategy had great importance to improve the quality standardization of ZN, and the method might be an efficiency tool for the discovery of active components in a complex system, such as TCMs.

The Construction of Folk Sports Featured Towns Based on Intelligent Building Technology Based on the Internet of Things.

With the emergence of the Internet of Things, technology and Internet thinking have entered traditional communities, and combined with traditional technologies, many new and better management methods and solutions have been born. Among them, the concept of intelligent buildings is also known to people. Based on big data technology, cloud computing technology, and Internet of Things technology, smart buildings provide smart and convenient devices and services for smart device users. The Internet of Things technology is entering our lives at an unimaginable speed. It has been applied in many fields. Smart home, smart transportation, smart medical, smart agriculture, and smart grid are widely used in the Internet of Things technology. The application of Internet of Things technology to the construction of folk sports characteristic towns is of great significance. The construction of folk sports characteristic towns and the protection of intangible cultural heritage have the same purpose and interoperability of elements as the development of traditional cities. From the perspective of protecting folk culture and intangible cultural heritage, it is effective to promote the development of small towns with folk custom characteristics. Based on the research on the construction of folk-custom sports towns, this paper proposes a series of data model analysis and analyzes the proportion of sports preferences in the survey of volunteers in the folk-custom sports towns. The final result of the research shows that the ball games sports personnel accounted for the largest proportion, with 156 people accounting for 48.15%. This shows that about half of the people like ball sports, which proves that ball sports should be the mainstay of folk sports towns, and other sports should be supplemented by other sports.

10.6-µm infrared laser as adjuvant therapy for diabetic peripheral neuropathy: study protocol for a double-blind, randomized controlled trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common chronic neurological complication. It is the main cause of disability in diabetes mellitus (DM) patients and seriously affects the quality of life of patients. Pharmacological treatments always associate with limited efficacy and adverse effects. Moxibustion has been recommended to treat DPN as an adjuvant therapy to conventional medical treatment to accelerate alleviation of the symptoms of DPN. 10.6-µm laser moxibustion (LM), whose wavelength is close to the peak of infrared radiation spectrum of the traditional moxibustion as well as human acupoints, produces the thermal effect similar with moxibustion but with no smoke or smell. The purpose of this sham controlled clinical trial is to determine the effect and safety of 10.6-µm LM as adjuvant therapy in patients with DPN. METHODS: This is a protocol for a randomized, double-blind, sham-controlled trial. One hundred fourteen patients meeting the inclusion and exclusion criteria will be recruited and randomly assigned to the LM group or the sham LM group with a 1:1 allocation ratio. Patients in both groups will receive a basic integrated treatment of Chinese and Western medicine and a total of 12 sessions of true or sham LM treatments over 4 weeks with 3 sessions a week. The primary outcome is nerve conduction velocity (NCV), and the secondary outcomes include Michigan Neuropathy Screening Instrument (MNSI) scores, Diabetes-Specific Quality of Life (DSQL) scores, blood rheology parameters, and assessments of safety and blinding. Outcome measures will be collected at baseline, 2 weeks after treatment, the end of LM treatments (4 weeks), and 4, 8 weeks after the end of LM treatment (8, 12weeks). DISCUSSION: This study will be conducted to compare the efficacy of LM versus sham LM combined with medical treatment. 10.6-µm LM may alleviate symptoms, improve quality of life, and reduce the dosage of drugs as well as avoid causing serious side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000029329 . Registered on 25 January 2020.

Geraniol relieves mycoplasma pneumonia infection-induced lung injury in mice through the regulation of ERK/JNK and NF-κB signaling pathways.

BACKGROUND: Pneumonia is a serious pediatric lung injury disease caused by Mycoplasma pneumoniae (M. pneumoniae) with increasing global prevalence every year. The WHO has reported that nearly 19% of children die due to pneumonia worldwide. OBJECTIVE: The present research was conducted to discover the ameliorative properties of geraniol against M. pneumoniae-provoked pneumonia in mice through the modulation of inflammatory responses. METHODOLOGY: The pneumonia was provoked in the male Swiss albino mice via infecting animals with 100 µl of M. pneumoniae for 2 days and supplemented concurrently with 20 mg/kg of geraniol for 3 days. 100 mg/kg of azithromycin was used as a standard drug. The nitric oxide (NO) level and MPO activity were measured using kits. The SOD activity, GSH, and MDA levels were studied using standard methods. The polymerase chain reaction (PCR) study was performed to examine the M. pneumoniae DNA load. The inflammatory cytokines status was assessed by assay kits. The ERK1/2, JNK1/2, and NF-κB expressions were studied by reverse-transcription (RT-PCR). The lung tissues were analyzed microscopically to investigate the histological alterations. RESULTS: Geraniol treatment effectively reduced lung weight, NO level, and MPO activity in the pneumonia mice. The total cells and M. pneumoniae DNA load were also decreased by the geraniol. The SOD activity and GSH level were improved and MDA was decreased by the geraniol treatment. The IL-1, IL-6, IL-8, TNF-α, and TGF status were appreciably depleted by the geraniol in the pneumonia mice. Geraniol also suppressed the ERK1/2 and NF-κB expressions in the lung tissues. Histological findings also suggest the therapeutic roles of geraniol against pneumonia in mice. CONCLUSION: In summary, our results proved the beneficial roles of geraniol against the M. pneumoniae-provoked pneumonia. Geraniol could be a hopeful therapeutic agent to treat pneumonia in the future.

Comparing the efficacy of two different temperature stimulation in warm acupuncture on acute low back pain: A randomized controlled trial.

BACKGROUND: Warm acupuncture, a combination of the mechanical stimulation of acupuncture and thermal stimulation of moxibustion, is commonly used in treating acute low back pain (LBP). This trial aimed to compare the efficacy of stronger (above 43°C) and weaker (above 40°C) heat stimulation in warm acupuncture on the function and pain in patients with acute LBP due to lumbosacral disc degeneration (LDD). METHODS: One hundred and fifty-nine adults were randomly assigned to receive warm acupuncture treatment with silver needle (SvN) or with stainless steel needle (SSN) (1:1). Both groups received a 3-week therapy with 3 sessions per week. The primary outcome was the modified Oswestry Disability Index at week 4. The secondary outcomes included average pain, three physical sign tests and adverse events. Participants were followed up at week 16 and week 28 after randomization. RESULTS: The LBP related disability and pain intensity significantly relieved more in the SvN warm acupuncture group than in the SSN group, in both the short and long term (p<0.001). The between-groups difference in physical signs showed statistical significance only in the short term (p = 0.024), but not in long term (p = 0.081; p = 0.069). CONCLUSION: Compared with warm acupuncture with stainless-steel needle at above 40°C, warm acupuncture with silver needle at above 43°C relieved more disability and pain in patients with acute LBP due to LDD. STUDY REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1800019051).

Comparison of 10.6 µm Laser Moxibustion with Traditional Moxibustion in Knee Osteoarthritic Therapy: A Randomized Noninferiority Clinical Trial.

Objective: To investigate the noninferiority of 10.6 µm laser moxibustion (LM) to traditional moxibustion (TM) in knee osteoarthritis (KOA). Methods: Ninety-two patients were recruited and randomly placed into one of two groups: 10.6 µm LM or TM in a 1:1 ratio. Each patient received 12 sessions of LM or TM, focusing on the ST-35 and Ashi acupoint. The sessions took place over 4 weeks, three times a week, and were followed up over 8 weeks. The endpoint outcomes were separated into two categories, primary and secondary. The primary endpoint was assessed at the end of the 4-week treatment, using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. The secondary endpoint was evaluated at the end of the trial and consisted of the WOMAC function and stiffness score, visual analog pain [visual analog scale (VAS)] score, and 15-m walking time test. In addition, safety evaluation was performed throughout the trial. Results: Among the 92 randomized participants, 86 (93.48%) completed the trial; 43 in each group. The WOMAC pain score improved dramatically between the LM and TM groups, with a mean difference of 20.61 [95% confidence interval (CI): -2.28 to 43.50]. Given that the lower boundary of 95% CI was greater than -18.49, noninferiority was established. In addition, both LM and TM significantly decreased the WOMAC (pain, function and stiffness) score, VAS score (p < 0.05), and the 15-m walking time at the end of the trial. Interestingly, there were not significant differences between LM and TM (p > 0.05), suggesting that both are equally effective in treating KOA. Finally, among the 92 patients, 17 (18.48%) adverse effects were documented, namely 5 (10.87%) in the LM-treated group and 11 (26.09%) in the TM-treated group. Conclusions: 10.6 µm LM is not inferior to TM in treating KOA. Moreover, both LM and TM dramatically alleviated knee pain and enhanced function of knees. Clinical Trial Registration number: ISRCTN registry trial identifier: 14604492.

A comprehensive review on traditional uses, chemical compositions, pharmacology properties and toxicology of Tetrastigma hemsleyanum.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg (T.hemsleyanum), a rare herbal plant distributed in subtropical areas of mainland China, has become a focus of scientific attention in recent years because of its high traditional value, including uses for treatment of children with fever, pneumonia, asthma, rheumatism, hepatitis, menstrual disorders, scrofula, and pharynx pain. AIM: This systematic review aims to provide an insightful understanding of traditional uses, chemical composition, pharmacological effect and clinical application of T. hemsleyanum, and lay a foundation for the further study and for the utilization of T. hemsleyanum resource. MATERIALS AND METHODS: A domestic and overseas literature search in known databases was conducted for published articles using the relevant keywords. RESULTS: One hundred and forty-two chemical constituents identified from T. hemsleyanum have been reported, including flavonoids, phenolic acids, polysaccharide, organic acids, fatty acids, terpenoids, steroids, amino acid and others. Among these components, flavonoids and polysaccharides were the representative active ingredients of T. hemsleyanum, which have been widely investigated. Modern pharmacological studies have shown that these components exhibited various pharmacological activities, such as anti-inflammatory, antioxidant, antivirus, antitumor, antipyretic, anti-hepatic injury, immunomodulatory, antibacterial etc. Moreover, different toxicological studies indicated that the clinical dosage of T. hemsleyanum was safe and reliable. CONCLUSIONS: Modern pharmacological studies have well supported and clarified some traditional uses, and T. hemsleyanum has a good prospect for the development of new drugs due to these outstanding properties. However, the present findings did not provide an in-depth evaluation of bioactivity of the extracts, the composition of its active extracts was not clear. Moreover, they were insufficient to satisfactorily explain some mechanisms of action. Data regarding many aspects of T. hemsleyanum, such as links between the traditional uses and bioactivities, pharmacokinetics, quality control standard and the clinical value of active compositions is still limited which need more attention.

Effect of Laser Moxibustion for Knee Osteoarthritis: A Multisite, Double-blind Randomized Controlled Trial.

OBJECTIVE: To examine the effects of laser moxibustion on pain and function in patients with knee osteoarthritis (OA). METHODS: A double-blind randomized clinical trial (4-week treatment, 20-week follow-up) was conducted. A total of 392 symptomatic knee OA patients with moderate to severe clinically significant knee pain were randomly assigned to laser treatment or sham laser control group (1:1). Twelve sessions of laser moxibustion or sham laser treatments on the acupuncture points at the affected knee(s) were performed 3 times a week for 4 weeks. The primary outcome measurement was change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to Week 4. RESULTS: Among the 392 randomized participants, 364 (92.86%) completed the trial. The median WOMAC pain score decreased significantly at Week 4 in the active group than in the sham group (2.1, 95% CI 1.6-2.6, P < 0.01). At Week 24, compared to the sham laser, active laser treatment resulted in significant pain reduction and function improvement (3.0, 95% CI 2.5-3.6, P < 0.01, and 14.8, 95% CI 11.9-17.6, P < 0.01, respectively). The physical component of the quality of life significantly improved in the active group vs the sham controls at Week 4 (3.2, 95% CI 1.3-5.0, P = 0.001) up to Week 24 (5.1, 95% CI 3.3-7.0, P < 0.001). No serious adverse effects were reported. CONCLUSION: Laser moxibustion resulted in statistically and clinically significant pain reduction and function improvement following a 4-week treatment in patients with knee OA.

Self-Propelled and Near-Infrared-Phototaxic Photosynthetic Bacteria as Photothermal Agents for Hypoxia-Targeted Cancer Therapy.

Hypoxia can increase the resistance of tumor cells to radiotherapy and chemotherapy. However, the dense extracellular matrix, high interstitial fluid pressure, and irregular blood supply often serve as physical barriers to inhibit penetration of drugs or nanodrugs across tumor blood microvessels into hypoxic regions. Therefore, it is of great significance and highly desirable to improve the efficiency of hypoxia-targeted therapy. In this work, living photosynthetic bacteria (PSB) are utilized as hypoxia-targeted carriers for hypoxic tumor therapy due to their near-infrared (NIR) chemotaxis and their physiological characteristics as facultative aerobes. More interestingly, we discovered that PSB can serve as a kind of photothermal agent to generate heat through nonradiative relaxation pathways due to their strong photoabsorption in the NIR region. Therefore, PSB integrate the properties of hypoxia targeting and photothermal therapeutic agents in an "all-in-one" manner, and no postmodification is needed to achieve hypoxia-targeted cancer therapy. Moreover, as natural bacteria, noncytotoxic PSB were found to enhance immune response that induced the infiltration of cytotoxicity T lymphocyte. Our results indicate PSB specifically accumulate in hypoxic tumor regions, and they show a high efficiency in the elimination of cancer cells. This proof of concept may provide a smart therapeutic system in the field of hypoxia-targeted photothermal therapeutic platforms.

[Remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease].

OBJECTIVE: To explore the feasibility of remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease. METHODS: Forty six neonates of gestational age >35 weeks with ABO hemolytic disease admitted to Women's Hospital, Zhejiang University School of Medicine from January 20th, 2020 to February 29th, 2020 were enrolled in the study (study group). The newborns were followed up at home after discharge, the transcutaneous bilirubin (TCB) levels were measured by parents using the provided device and the results were sent to the doctor by smart phone using the installed APP. Fifty six newborns with ABO hemolytic disease admitted in 2018 who received conventional outpatient follow-up after discharge served as the control group. The demographic characteristics, total serum bilirubin (TSB) level during hospitalization, number of outpatient visit and rate of re-admission due to rebound hyperbilirubinemia were compared between the two groups. RESULTS: There were no significant differences between the two groups in gestational age, birth weight, delivery mode, gender, length of the first hospitalization, TSB level before phototherapy and before discharge, and the managements during the first hospitalization (all P>0.05). Compared with the control group, TSB level before readmission [(265±16) µmol/L vs. (295±15) µmol/L] and the number of outpatient visits (1.3±0.8 vs. 3.8±0.5) were significantly lower in the study group (all P<0.01), while the rate of readmission (17.4%vs. 12.5%) and the weight at the time of readmission[(3398±452) g vs. (3477±324) g] were not significantly different (all P>0.05). No cases of acute bilirubin encephalopathy occurred in both groups. CONCLUSIONS: The remote follow-up for neonatal jaundice at home can effectively reduce the number of outpatient visits without increasing the risk of readmission and severe neonatal hyperbilirubinemia for newborns with ABO hemolytic disease.

Acupuncture for diabetic peripheral neuropathy: study protocol for a randomized, placebo-controlled trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes mellitus that has a considerable impact on quality of life, but there are few effective therapeutic strategies. The aim of this trial is to determine the efficacy and safety of manual acupuncture (MA) versus sham acupuncture (SA) for DPN. METHODS/DESIGN: This is a study protocol for a randomized, placebo-controlled clinical trial. A total of 118 patients with DPN will be recruited and randomly assigned in a 1:1 ratio to either the MA group or SA group. All patients will receive 24 sessions over 12 weeks. Participants will complete the trial by visiting the research center at month 6 for a follow-up assessment. The primary outcome is peroneal motor nerve conduction velocity (peroneal MNCV) at week 12 compared with baseline. Secondary outcomes include peroneal motor nerve action potential amplitude (peroneal MNAP) and latent period (peroneal MNLP), sural sensory nerve conduction velocity (sural SNCV), action potential amplitude (sural SNAP) and latent period (sural SNLP), fasting plasma glucose (FPG), 2-h postprandial blood glucose (2hPG), glycated hemoglobin (HbAlc) at week 12 compared with baseline, Michigan Neuropathy Screening Instrument (MNSI) score and Diabetes Specific Quality of Life scale (DSQL) at week 12 and month 6 compared with baseline. Safety will be assessed during the whole trial. Masking effectiveness will be assessed by patients. DISCUSSION: This trial may provide high-quality evidence for evaluating the efficacy and safety of MA treatment for DPN compared with SA treatment. Results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR1800020444. First registered on 29 December 2018, retrospectively registered, http://www.chictr.org.cn/showproj.aspx?Proj=31063 .

Efficient Synthesis of Structured Phospholipids Containing Short-Chain Fatty Acids over a Sulfonated Zn-SBA-15 Catalyst.

Catalytic production of structured phospholipids (SPLs) containing short-chain fatty acids (SCFAs) in an efficient heterogeneous manner is of great importance from the standpoint of food engineering. Herein, a bifunctionalized sulfonated Zn-SBA-15 catalyst was studied for SPL synthesis through interesterification of soybean lecithin with ethyl propionate or methyl butyrate. Various characterization techniques such as pyridine Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and ultraviolet-visible diffuse reflectance spectroscopy were conducted to determine the physicochemical properties, so as to build the possible structure-reactivity relationship of the catalyst. In screening tests with commercial Amberlyst-15 or other SBA-15-type materials, the as-prepared sample showed promising catalytic performance probably owing to its mesoporous structure and cooperative role of Brönsted and Lewis acid sites. Notably, the sample was easily separated and recycled without obvious deactivation. In general, the investigated catalyst was regarded as one of the promising alternatives to otherwise expensive biocatalysts for SCFA-containing SPL production.

Fermented barley extracts with Lactobacillus plantarum dy-1 decreased fat accumulation of Caenorhabditis elegans in a daf-2-dependent mechanism.

Barley, a kind of cereal, is rich in polysaccharides, phenols, proteins, ß-glucan, etc. Our previous studies discovered that extracts from Lactobacillus plantarum dy-1-fermented barley (LFBE) held strong anti-obesity property in obese rats through inhibiting inflammation and suppressing the differentiation in 3T3-L1 preadipocytes; however, the precise mechanism of LFBE regulating lipid metabolism remains elusive. Results suggested LFBE and its main active components, especially the total phenols, exhibited fat-lowering effects in glucose treated Caenorhabditis elegans at a certain concentration. Additionally, LFBE and the main components changed related genes in the insulin signaling pathway, fatty acid oxidation, and synthesis. Following verification study using mutants confirmed that the daf-2 gene rather than the daf-16 gene was required in LFBE and main components regulating lipid metabolism, which also involved in the process of fatty acid ß-oxidation and unsaturated fatty acid synthesis. Results demonstrated that LFBE and its main bioactivate compounds inhibited fat accumulation partly in a daf-2-dependent mechanism. PRACTICAL APPLICATIONS: Our previous studies have reported that extracts of fermented barley exhibited anti-obesity activity. However, little is known about which functional factors play a leading role in decreasing fat deposition and its precise mechanism. Results indicated that daf-2 mediated signaling pathways involved in the fat-lowering effects of LFBE and its main components. Our findings are beneficial to understand the main nutritional ingredients in LFBE which are ideal and expected in functional foods for the obese.

The efficacy of jade moxibustion in knee osteoarthritis.

INTRODUCTION: This study aims to compare clinical effect between Jade moxibustion and traditional moxibustion, and to determine the clinical effect of Jade moxibustion on knee osteoarthritis (KOA). METHODS/DESIGN: This is a 2-parallel-group, randomized controlled trial. A total of 148 subjects with KOA (Kellgren-Lawrence grade II or III) will be recruited and randomized to receive Jade moxibustion treatment or a traditional moxibustion treatment in a 1:1 ratio. Jade moxibustion group: The affected knee of the subjects will be covered with jade kneepad. Traditional moxibustion group: Chosen the ST35, ST34, EX-LE4, SP10 and Ashi points at the affected knee. The subjects will receive treatment three times a week, altogether 12 times in 4 weeks. The main outcomes are WOMAC knee pain score, knee function score and SF-36 quality of life questionnaire changes at the 4th week. Secondary outcomes include WOMAC knee pain score and knee function score, overall clinical efficacy evaluation, medication, safety evaluation at the 2nd, 12th, and 24th week, and cytokines related to osteoarthritis in serum. DISCUSSION: This randomized controlled trial used traditional moxibustion as a control group to provide rigorous evidence for the clinical efficacy and safety of Jade moxibustion in treatment of KOA. TRIAL REGISTRATION: ISRCTN registry, No 21174552. Registered on 28 February 2020.