A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy

The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.

Engineering CeO_(2)/CuO heterostructure anchored on upconversion nanoparticles with boosting ROS generation-primed apoptosisferroptosis for cancer dynamic therapy

Highly toxic reactive oxygen species(ROS)induced apoptosis and ferroptosis have been considered as significant cell death pathways for cancer therapy.However,insufficient amount of intracellular ROS extremely restricts the therapeutic effect.Toward this,we report a rationally designed nanocomposite(mUCC)with enhanced ROS generation ability,inducing the combination of apoptosis and ferroptosis through synergistic photodynamic therapy(PDT)and chemodynamic therapy(CDT).Under 808 nm near-infrared(NIR)light irradiation,photocatalytic reaction is triggered starting from the separation of electron-hole pairs on the surface of heterojunction(CeO_(2)/CuO),realizing improved ROS production.Simultaneously,mUCC served as Fenton-like agent exhibits considerable ability to generate highly toxic·OH under tumor microenvironment(TME).The boosted accumulation of ROS disrupts the redox balance within tumor cells and results in the integration of apoptosis and ferroptosis.In addition,mUCC shows satisfactory tumor targeting property benefiting from the cancer cell membrane functionalization under the guidance of magnetic resonance imaging(MRI)and NIR fluorescence imaging.The intelligent mUCC with good biocompatibility and excellent antitumor response achieves efficient tumor elimination under synergistic PDT and CDT.This work offers an elective approach for further development of ROS-based therapeutic nanoplatform in cancer therapy.

Mn-doped Ti-based MOFs for magnetic resonance imaging-guided synergistic microwave thermal and microwave dynamic therapy of liver cancer

Currently,precise ablation of tumors without damaging the surrounding normal tissue is still an urgent problem for clinical microwave therapy of liver cancer.Herein,we synthesized Mn-doped Ti MOFs(Mn-Ti MOFs)nanosheets by in-situ doping method and applied them for microwave therapy.Infrared thermal imaging results indicate Mn-Ti MOFs can rapidly increase the temperature of normal saline,attributing to the porous structure improving microwave-induced ion collision frequency.Moreover,Mn-Ti MOFs show higher 1O2 output than Ti MOFs under 2 W of low-power microwave irradiation due to the narrower band-gap after Mn doping.At the same time,Mn endows the MOFs with a desirable T1 contrast of magnetic resonance imaging(r2/r1=2.315).Further,results on HepG2 tumor-bearing mice prove that microwave-triggered Mn-Ti MOFs nearly eradicate the tumors after 14 days of treatment.Our study offers a promising sensitizer for synergistic microwave thermal and microwave dynamic therapy of liver cancer.

Spatiotemporally dynamic therapy with shape-adaptive drug-gel for the improvement of tissue regeneration with ordered structure

A spatiotemporally dynamic therapy(SDT)is proposed as a powerful therapeutic modality that provides spatially dynamic responses of drug-carriers for adapting to the wound microenvironment.Herein,dynamic chitosan-poly(ethylene glycol)(CP)Schiff-base linkages are employed to perform SDT by directly converting a liquid drug Kangfuxin(KFX)into a gel formation.The obtained KFX-CP drug-gel with shape-adaptive property is used to treat a representative oral mucositis(OM)model in a spatiotemporally dynamic manner.The KFX-CP drug-gel creates an instructive microenvironment to regulate signaling biomolecules and endogenous cells behavior,thereby promoting OM healing by the rule of dynamically adjusting shape to fit the irregular OM regions first,and then provides space for tissue regeneration,over KFX potion control and the general hydrogel group of CP hydrogel and KFX-F127.Most interestingly,the regenerated tissue has ordered structure like healthy tissue.Therefore,the SDT provides a new approach for the design of next generation of wound dressing and tissue engineering materials.

Metaphysical Energy Therapy in the Treatment of Cranial Nerve Palsies with Special Reference to Bell’s Palsy

Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (also named mononeuropathy). Com- monly 2 cranial nerves Viz., cranial nerve VII and cranial nerve VI are involved in facial nerve palsies. The former one is called Bell’s palsy and is acute Lower Motor Neuron facial nerve paralysis (>80%) causing an inability to control facial muscles on the affected side. The later one is sixth nerve palsy, (the abducens nerve), which is responsible for triggering contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye resulting in double vision on the affected side. In recent times, we have found to our amazement, rapid restoration of normalcy within a few hours to a few days, of Cranial Nerve palsies in diabetic subjects at our centre. We are presenting a group of cases having Type2DM over different time periods from 6 to 20 years and those who suddenly suffered facial nerve palsy and they came to VHSDRC for treatment. They were started on the new modality called the Dynamic Acupuncture Mediated Meta-physical Energy Therapy (DAMM Therapy), to recover from the facial palsy. The DAMM therapy is a unique novel way of infusing and transferring healing energy from the therapist to the patient. Within 2 - 7 sittings of DAMM therapy patients showed 75% - 100% improvement in their clinical condition.

OBSERVATION ON THE THERAPEUTIC EFFECT OF ACPUNCTURE COMBINED WITH MASSAGE FOR CERVICAL SPONDYLOSIS OF VERTEBRAL ARTERIAL TYPE BY USING TRANCRANIAL DOPPLYER ULTRASONOGRAPHY

To observe the effect of acupuncture combined with massage on blood flow velocity of the vertebro-basilar artery in cervical spondylosis of vertebral arterial type （CSVAT） patients. Methods： In the present study, methods of evidence-based medicine, triple-centers, single-blindness, randomization and control were used. A total of 100 cases of CSVAT patients were randomized into acupuncture plus massage （acu-massage） group （n = 38）, acupuncture group （n = 32） and massage group （n = 30）. Acupoints used were Fengchi （风池, GB 20）, cervical Jiaji （颈夹脊 EX-B 2）, Baihui （百会 GV 20）, and the methods of massage used were kneading-rolling, adhesion-separating and acupoint-digital pressing, topical digital pressing and rubbing, traction-extending and mild palm-rubbing. The treatment was conducted once daily, with 7 sessions being a therapeutic course and continuously for 2 courses. Changes of peak velocity （Vp）, end-diastolic velocity （Vd）, mean velocity （Vm） of blood flow of the vertebral artery （VA） and basilar artery （BA）, etc were detected before and after the treatment by using transcranial Doppler （TCD） ultrasonography. Resuits： After the treatment, the abnormally low Vp of both VA and BA in acu-massage, acupuncture and massage groups, Vm of VA in acu-massage and acupuncture groups, Vm of BA in acu-massage and massage groups, and Vd of VA and BA in the 3 groups all increased significantly in comparison with their own pretreatment（ P 〈 0.05, 0.01）, and the therapeutic effects of acu-massage group in the 3 indexes were significantly superior to those of acupuncture group and/or massage group （P 〈0.05, 0.01 ）. The abnormally increased Vp of VA in acu-massage and acupuncture groups, Vm of VA in the 3 groups, and Vd of VA in acu-massage and massage groups decreased obviously after the treatment in comparison with their own pretreatment （P 〈 0.05, 0.01）, and the therapeutic effects of acu-massage group were significantly superior to those of acupuncture and/or massage group in the 3 indexes of VA （P〈0.05, 0.01）. In addition, the abnormally increased Vp, Vm and Vd of BA in the 3 groups showed a similar tendency. No significant differences between acupuncture and massage groups in 3 indexes （ P 〉0.05）. Conclusion： The therapeutic effects of acupuncture plus massage is significantly superior to those of simple acupuncture and simple massage therapies in improving abnormal blood dynamics of vertebral and basilar arteries in CSVAT patients.

Design and therapeutic application of sodium alginate-based hydrogel with biodegradability and catalytic activity

How to efficiently treat cancer in a minimally invasive manner has become one of the major focuses of recent developments in biomedicine.In this research,biodegradable sodium alginate(SA)hydrogel encapsulated with NaHCO_(3)and glucose oxidase(GOX)was synthesized using Fe^(3+)as the crosslinker for the tumor chemodynamic therapy(CDT)and starvation therapy(ST).Material safety assessments revealed that this hydrogel possesses good in vitro and in vivo security.In tumor microenvrionment(TME),the Fe^(3+)further reacted with the intracellular glutathione and was transformed into Fe^(2+),which triggered the Fenton reaction with the H_(2)O_(2)within TME and produced abundant highly toxic·OH(hydroxyl radicals)for efficient tumor CDT.Furthermore,the GOXcatalyzed the enzymolysis of glucose to consume the nutrient of the tumor and enhance the H_(2)O_(2)level in TME.Besides,the CO_(2)bubbles that were generated from the decomposing of NaHCO_(3)promoted the contact between glucose and GOX.Findings in this research would have important implications for the present status of tumor therapy.

Research methods in complementary and alternative medicine： an integrative review

The scientific literature presents a modest amount ot evidence m the use or complementary ana al[erna- tire medicine （CAM）. On the other hand, in practice, relevant results are common. The debates among CAM practitioners about the quality and execution of scientific research are important, Therefore, the aim of this review is to gather, synthesize and describe the differentiated methodological models that encompass the complexity of therapeutic interventions. The process of bringing evidence-based medicine into clinical practice in CAM is essential for the growth and strengthening of complementary medicines worldwide.