Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

A review of complications of polyacrylamide hydrogel injection

Once a popular injectable filler,polyacrylamide hydrogel(PAAG)has been banned in China since 2006 due to its unclear safety and long-term complications.However,it is still being used worldwide because of its huge commercial profit,leading to emerging complications and an urgent need for standardized clinical management.This review aimed to assess the properties,safety,and complications of PAAG and treatment strategies for its removal.

Revolutionizing diabetic wound healing:The power of microneedles

Diabetic wounds significantly affect patient quality of life.Microneedles are a promising treatment to accelerate wound healing owing to their high drug-loading capacity and efficient drug delivery;however,few studies to date have comprehensively reviewed microneedles for diabetic wound healing.This up-to-date review summarizes the research progress in microneedles for diabetic wound healing,including manufacturing materials and techniques,structures,designs,release mechanisms,delivery substances,and their specific effects.This study showed that most microneedles designed for diabetic wounds are made of synthetic polymers and/or natural materials using polydimethylsiloxane micromolding.The geometric structure and design directly influence penetration ability and drug delivery capacity.Microneedles can deliver antibiotics,hypoglycemic agents,traditional Chinese medicines,metal ions,growth factors,exosomes,stem cells,and microorganisms,thus promoting diabetic wound healing through diverse mechanisms,such as antibacterial,anti-inflammatory,antioxidant,hypoglycemic,and angiogenic activities,at different stages of the healing process.In conclusion,microneedles are promising drug delivery systems for the treatment of diabetic wounds.

Oral health-related quality of life between Chinese and American orthodontic patients: A two-center cross-sectional study

Background:Although oral health-related quality of life(OHRQoL)in orthodontic patients has been assessed in the past,to date,no study has compared the OHRQoL between two nations.We aimed to compare the OHRQoL between Chinese and American orthodontic patients.Methods:We conducted a two-center questionnaire-based cross-sectional study among patients who underwent orthodontic treatments at the Chinese PLA General Hospital(PLAGH)in Beijing,China and Massachusetts General Hospital(MGH)in Boston,Massachusetts,United States.Candidate variables included the participating center,patients’age,sex,Angle’s classification of malocclusion,evaluation stage,and appliances used.The primary outcome was patients’OHRQoL assessed with the Oral Health Impact Profile-14(OHIP-14).Descriptive statistics,stratification,and univariate and multivariate analyses were performed.Results:The average age was lower for PLAGH patients than for MGH patients(21.1±7.9 vs.33.1±14.6 years,P<0.001).The most common type of malocclusion was Angle’s Class III malocclusion at PLAGH(39%)and Class I malocclusion at MGH(59.5%).Clear aligners were used in 34.1%and 2.7%of the patients at MGH and PLAGH,respectively.OHIP-14 scores were lower for PLAGH patients than for MGH patients(18.4±4.7 vs.22.3±7.4,P<0.001),particularly in functional limitation,psychological discomfort/disability,and handicap.Univariate regression analysis demonstrated that participating center,age,Class I malocclusion,and the use of clear aligners were significantly associated with overall OHIP-14 scores.Multivariate regression analysis demonstrated that patients at PLAGH were associated with lower OHIP-14 scores(coefficient:-3;95%CI:-5,-1.3;P=0.001),and age was positively associated with OHIP-14 scores(coefficient:0.1;95%CI:0.004,0.13;P=0.038).Conclusion:Chinese orthodontic patients had lower OHIP-14 scores,indicating a higher OHRQoL than American patients.In addition to the younger age,this difference may be attributed to the different ethical,cultural,educational,and socioeconomic background of Chinese and American orthodontic patients.

Nasolabial perforator flap for nasal defects

Nasal defects can be reconstructed with a nasolabial perforator flap,resulting in good aesthetic outcomes based on the facial subunit principle,owing to the combined advantages of the traditional nasolabial flap and the perforator flap.However,the localization of perforators makes the clinical application of a nasolabial perforator flap difficult.This review aims to provide a comprehensive summary of the nasolabial perforator flap from anatomical,methodological,and clinical application aspects,intending to provide plastic surgeons with a reference on conducting nasal reconstruction with a nasolabial perforator flap.

Complications Following Facial Thread-Lifting

Background Facial thread-lifting(FTL)is a minimally invasive facial rejuvenation technique.However,to date,no study has focused on the treatment of complications associated with FTL.The purpose of this study was to report on clinical manifestations of complications following FTL and their treatment methods.Methods We retrospectively reviewed the electronic medical records of patients who presented with complications of FTL.Patient demographics,medical history,types and clinical manifestations of complications,imaging,treatment methods,histopathological findings,and follow-up information were collected.Descriptive statistical analysis was performed.Results Our sample included 61 patients,all women,with a mean age of 36.3±8.9 years.The most common reason for consultation was infection(31.2%),followed by dissatisfaction with postoperative facial contour(23%),paresthesia(19.7%),dimpling and irregularity(16.4%),subcutaneous induration(13.1%),thread extrusion(4.9%),and facial nerve injury(3.3%).Fifty-one(83.6%)patients reported alleviated symptoms after receiving pharmaceutical and physical therapies.Surgical interventions,including debridement and thread removal,were required in 10 patients(16.4%).Threads were completely or partially removed in 5 patients within 3 months of the initial FTL.During a median follow-up of 1.7 years,9 patients recovered well and were satisfied with the clinical outcomes,whereas one patient was unsatisfied due to dimpling and scarring.Conclusions The results show that most complications after FTL can be treated nonsurgically.Revision surgery is recommended for patients with recurrent infection,thread extrusion,and subcutaneous induration.Aesthetic surgeons and dermatologists should comply with the indications for FTL and optimize surgical procedures to minimize the risk of complications.

3D-printed models improve surgical planning for correction of severe postburn ankle contracture with an external fixator

Gradual distraction with an external fixator is a widely used treatment for severe postburn ankle contracture(SPAC).However,application of external fixators is complex,and conventional two-dimensional(2D)imaging-based surgical planning is not particularly helpful due to a lack of spatial geometry.The purpose of this study was to evaluate the surgical planning process for this procedure with patient-specific three-dimension-printed models(3DPMs).In this study,patients coming from two centers were divided into two cohorts(3DPM group vs.control group)depending on whether a 3DPM was used for preoperative surgical planning.Operation duration,improvement in metatarsal-tibial angle(MTA),range of motion(ROM),the American Orthopedic Foot and Ankle Society(AOFAS)scores,complications,and patient-reported satisfaction were compared between two groups.The 3DPM group had significantly shorter operation duration than the control group((2.0±0.3)h vs.(3.2±0.3)h,P<0.01).MTA,ROM,and AOFAS scores between the two groups showed no significant differences pre-operation,after the removal of the external fixator,or at follow-up.Plantigrade feet were achieved and gait was substantially improved in all patients at the final follow-up.Pin-tract infections occurred in two patients(one in each group)during distraction and were treated with wound care and oral antibiotics.Patients in the 3DPM group reported higher satisfaction than those in the control group,owing to better patient-surgeon communication.Surgical planning using patient-specific 3DPMs significantly reduced operation duration and increased patient satisfaction,while providing similar improvements in ankle movement and function compared to traditional surgical planning for the correction of SPAC with external fixators.

Harnessing the synergy of perfusable muscle flap matrix and adipose-derived stem cells for prevascularization and macrophage polarization to reconstruct volumetric muscle loss

Muscle flaps must have a strong vascular network to support a large tissue volume and ensure successful engraftment.We developed porcine stomach musculofascial flap matrix(PDSF)comprising extracellular matrix(ECM)and intact vasculature.PDSF had a dominant vascular pedicle,microcirculatory vessels,a nerve network,well-retained 3-dimensional(3D)nanofibrous ECM structures,and no allo-or xenoantigenicity.In-depth proteomic analysis demonstrated that PDSF was composed of core matrisome proteins(e.g.,collagens,glycoproteins,proteoglycans,and ECM regulators)that,as shown by Gene Ontology term enrichment analysis,are functionally related to musculofascial biological processes.Moreover,PDSF􀀀human adipose-derived stem cell(hASC)synergy not only induced monocytes towards IL-10􀀀producing M2 macrophage polarization through the enhancement of hASCs’paracrine effect but also promoted the proliferation and interconnection of both human skeletal muscle myoblasts(HSMMs)and human umbilical vein endothelial cells(HUVECs)in static triculture conditions.Furthermore,PDSF was successfully prevascularized through a dynamic perfusion coculture of hASCs and HUVECs,which integrated with PDSF and induced the maturation of vascular networks in vitro.In a xenotransplantation model,PDSF demonstrated myoconductive and immunomodulatory properties associated with the predominance of M2 macrophages and regulatory T cells.In a volumetric muscle loss(VML)model,prevascularized PDSF augmented neovascularization and constructive remodeling,which was characterized by the predominant infiltration of M2 macrophages and significant musculofascial tissue formation.These results indicate that hASCs’integration with PDSF enhances the cells’dual function in immunomodulation and angiogenesis.Owing in part to this PDSF-hASC synergy,our platform shows promise for vascularized muscle flap engineering for VML reconstruction.