Tofacitinib combined with local low-dose ixekizumab injection benefits those with peripheral psoriatic arthritis

Dear Editor,Treating psoriatic arthritis(PsA)is always difficult.Systemic treatments can be administered either orally or through intramuscular and intra-articular injection,including conventional synthetics,biologics and targeted synthetic disease-modifying antirheumatic drugs[1].The alternatives,topical external therapies,are not effective on joint lesions due to drug permeability issues.Drugs injected into the articular cavity are also unsuitable for small peripheral joint lesions,the most common manifestations of PsA.The limited treatment options for PsA present a challenge.

Navigating the pathways:TAR-DNA-binding-protein-43 aggregation,axonal transport,and local synthesis in amyotrophic lateral sclerosis pathology

Neurons are highly polarized cells with axons reaching over a meter long in adult humans.To survive and maintain their proper function,neurons depend on specific mechanisms that regulate spatiotemporal signaling and metabolic events,which need to be carried out at the right place,time,and intensity.Such mechanisms include axonal transport,local synthesis,and liquid-liquid phase separations.Alterations and malfunctions in these processes are correlated to neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS).

Refractory lipoatrophy treated with autologous whole blood injection:A case report

BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.

Understanding the local structure and thermophysical behavior of Mg-La liquid alloys via machine learning potential

The local structure and thermophysical behavior of Mg-La liquid alloys were in-depth understood using deep potential molecular dynamic(DPMD) simulation driven via machine learning to promote the development of Mg-La alloys. The robustness of the trained deep potential(DP) model was thoroughly evaluated through several aspects, including root-mean-square errors(RMSEs), energy and force data, and structural information comparison results;the results indicate the carefully trained DP model is reliable. The component and temperature dependence of the local structure in the Mg-La liquid alloy was analyzed. The effect of Mg content in the system on the first coordination shell of the atomic pairs is the same as that of temperature. The pre-peak demonstrated in the structure factor indicates the presence of a medium-range ordered structure in the Mg-La liquid alloy, which is particularly pronounced in the 80at% Mg system and disappears at elevated temperatures. The density, self-diffusion coefficient, and shear viscosity for the Mg-La liquid alloy were predicted via DPMD simulation, the evolution patterns with Mg content and temperature were subsequently discussed, and a database was established accordingly. Finally, the mixing enthalpy and elemental activity of the Mg-La liquid alloy at 1200 K were reliably evaluated,which provides new guidance for related studies.

Generation of transgenic chicken through ovarian injection

Background : Traditional DNA microinjection methods used in mammals are difficult to apply to avian species due to their unique reproductive characteristics. Genetic manipulation in chickens, particularly involving immature follicles within living ovaries, has not been extensively explored. This study seeks to establish an efficient method for generating transgenic chickens through ovarian injection, potentially bypassing the challenges associated with primordial germ cell (PGC) manipulation and fertilized egg microinjection. Methods : Hens were anesthetized and underwent a surgical procedure to access the ovary for DNA injection into immature follicles. The study used liposomes to deliver GFP- expressing plasmids at various dosages. After injection, hens recovered, and their eggs were fertilized through artificial insemination. Results : Transgenic chickens were successfully generated in one generation without needing G0 founders. The injection of 20 μg plasmid yielded the highest transgenic efficiency at 12.1%. GFP- positive embryos were confirmed through microscopy, and successful transgene expression was validated at the tissue level using immunostain- ing. TERT and GFP elements introduced in the G1 generation resulted in 4.1% positive transgene rates, as confirmed by PCR and Southern blotting. Conclusion : This ovarian injection method offers a promising alternative for avian ge- netic manipulation, bypassing complex PGC procedures and enabling direct genera- tion of G1 transgenic chickens. This technique simplifies the transgenic process for chickens and has the potential to be adapted for other avian species, especially those without established PGCs culture systems.

Clinical observation on prognosis of mixed hemorrhoids treated with polidocanol injection combined with automatic elastic thread ligation operation

BACKGROUND A total of 100 patients diagnosed with mixed hemorrhoids from October 2022 to September 2023 in our hospital were randomly divided into groups by dice rolling and compared with the efficacy of different treatment options.AIM To analyze the clinical effect and prognosis of mixed hemorrhoids treated with polidocanol injection combined with automatic elastic thread ligation operation(RPH).METHODS A total of 100 patients with mixed hemorrhoids who visited our hospital from October 2022 to September 2023 were selected and randomly divided into the control group(n=50)and the treatment group(n=50)by rolling the dice.The procedure for prolapse and hemorrhoids(PPH)was adopted in the control group,while polidocanol foam injection+RPH was adopted in the treatment group.The therapeutic effects,operation time,wound healing time,hospital stay,pain situation(24 hours post-operative pain score,first defecation pain score),quality of life(QOL),incidence of complications(post-operative hemorrhage,edema,infection),incidence of anal stenosis 3 months post-operatively and recurrence rate 1 year post-operatively of the two groups were compared.RESULTS Compared with the control group,the total effective rate of treatment group was higher,and the difference was significant(P<0.05).The operation time/wound healing time/hospital stay in the treatment group were shorter than those in the control group(P<0.05).The pain scores at 24 hours after operation/first defecation pain score of the treatment group was significantly lower than those in the control group(P<0.05).After surgery,the QOL scores of the two groups decreased,with the treatment group having higher scores than that of the control group(P<0.05).Compared with the control group,the incidence of postoperative complications in the treatment group was lower,and the difference was significant(P<0.05);However,there was no significant difference in the incidence of postoperative bleeding between the two groups(P>0.05);There was no significant difference in the incidence of anal stenosis 3 months after operation and the recurrence rate 1 year after operation between the two groups(P>0.05).CONCLUSION For patients with mixed hemorrhoids,the therapeutic effect achieved by using polidocanol injection combined with RPH was better.The wounds of the patients healed faster,the postoperative pain was milder,QOL improved,and the incidence of complications was lower,and the short-term and long-term prognosis was good.

Local injection therapy for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC. Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%. DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, hasbeen widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm). CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.

Clinical Effects of Shenqi Fuzheng Injection in the Neoadjuvant Chemotherapy for Local Advanced Breast Cancer and the Effects on T-lymphocyte Subsets

Objective： To evaluate clinical effects of Shenqi Fuzheng Injection （参芪抉正注射液） in the neoadjuvant chemotherapy for local advanced breast cancer and the effects on T-lymphocyte subsets. Methods： During the period from 2000 to 2005, 126 patients with local advanced breast cancer were treated with the neoadjuvant chemotherapy. They were randomly divided into the following two groups： a control group of 61 cases treated by chemotherapy alone and a study group of 65 cases treated by chemotherapy plus Shenqi Fuzheng Injection, All the cases of both groups were given the CEF （CTX 500 mg/m^2, d1, 8; EP140 mg/m^2, d1, 8; and 5-Fu 500 mg/m^2, d1,8） regimen. The clinical effects, the effects on T-lymphocyte subgroup and NK cells, and the toxic side effects were observed. Results： All the patients completed two cycles of the chemotherapy, and the efficacy and the toxic side effects were evaluated. For the primary tumor in the breast, the total effective rate was 69.2% （45/65） in the study group and 49.2% （30/61） in the control group with a statistically significant difference in the intergroup comparison （x^2=5.251, P=0.022, 〈 0.05）. There was no progression of the disease in both the groups, and there were no grade IV toxic side effects in the two groups. The major toxic responses were myelosuppression and gastrointestinal reaction, which were milder in the study group than the control group, and with a shorter recovery course in the former than the latter. Besides, an obvious rise of the T-lymphocyte subgroup and NK cells was found in the study group after the neoadjuvant chemotherapy, with a very significant difference from the controls （P〈0.01）. Conclusions： Shenqi Fuzheng Injection can improve and regulate immune function of the patients with local advanced breast cancer given the neoadjuvant chemotherapy, and therefore it can enhance the curative effect and reduce the side effect as well.

Why Labor Epidural Causes Fever and Why Lidocaine Burns on Injection? Role of TRPV 1 Receptor in Hyperthermia: Possible Explanation of Mechanism of Hyperthermia during Labor Epidural and Burning Sensation on Injection of Local Anesthetics

The mechanisms of epidural-associated fever remain incompletely understood [1-3]. We propose that action of local anesthetic on TPRV1. The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor can explain this effect and explain mechanism of burning sensation on local anesthetic injected subcutaneously or intramuscular. Role of TRPV1 receptor was not discussed previously in Obstetric Anesthesia literature. Based on available data, we propose that Local Anesthetics work as agonist/antagonist on TPRV1 receptors. Antagonist action may cause hyperthermia through modifying thermoregulation [4], agonist action may cause hyperthermia thru release of IL-6 and other mediators of inflammation [5-10]. Agonist action may explain burning sensation on injection of Local Anesthetics. Burning sensation can be diminished by increasing pH of Local Anesthetic solution, because vanillin receptors are stimulated by acidification through lower pH [11,12].

Novel gene therapy for rheumatoid arthritis with single local injection: adeno-associated virus-mediated delivery of A_(20)/TNFAIP_(3)

Dear Editor,Multiple experiments have established TNF-α-induced protein 3 (A20/TNFAIP3) as a critical regulator associated with rheumatoid arthritis(RA)[1,2].The lack of TNF-α-induced protein 3 (A20) promotes the NOD-like receptor protein 3 (NLRP3) inflammasome and induces spontaneous arthritis,while increase of A20 reduces the secretion of IL-1β and favors immunological tolerance[3,4]. Hence, we investigate the feasibility of recombinant adeno-associated virus 6 (rAAV6)-mediated A20 gene therapy in a collageninduced arthritis (CIA) model.

Posterior pedicle screw fixation combined with local steroid injections for treating axial eosinophilic granulomas and atlantoaxial dislocation:A case report

BACKGROUND Eosinophilic granuloma(EG)is a proliferative condition that affects the cells of bone tissue.There are no specific clinical signs or imaging manifestations in the early stages of the disease,making it simple to overlook and misdiagnose.Because of the disease's rarity,there is presently no standardized treatment principle.There are few accounts of such occurrences affecting the axis among children.We discovered a case of a child whose EG resulted in atlantoaxial joint dislocation and destruction of the axial bone.CASE SUMMARY After having pharyngeal discomfort for more than six months without a clear explanation,a 6-year-old boy was brought to our hospital.Following a careful evaluation,the pathology indicated a strong likelihood of an axial EG.Ultimately,we decided to treat the boy with posterior pedicle screw fixation and local steroid injections.CONCLUSION EGs of the upper cervical spine are quite uncommon in children,and they are exceedingly easy to overlook or misdiagnose.Posterior pedicle screw fixation and local steroid injections are effective treatments for patients with axial EGs affecting the atlantoaxial junction.

Local non-similarity solution to impact of chemical reaction on MHD mixed convection heat and mass transfer flow over porous wedge in the presence of suction /injection

Combined heat and mass transfer on free, forced, and mixed convection flow along a porous wedge with magnetic effect in the presence of chemical reaction is investigated. The flow field characteristics are analyzed by the Runge-Kutta-Gill scheme with the shooting method as well as the local non-similarity method up to the third level of truncation, which are used to reduce the governing partial differential equations into nine ordinary differential equations. The governing boundary layer equations are converted to a dimensionless form by Falkner-Skan transformations. Because of the effect of suction/injection on the wall of the wedge with buoyancy force and variable wall temperature, the flow field is locally non-similar. Numerical calculations up to the third order level of truncation are carried out as a special case for different values of dimensionless parameters. Effects of the magnetic field strength in the presence of chemical reaction with variable wall temperature and concentration on the dimensionless velocity, temperature and concentration profiles are shown graphically.

The effectiveness of local anesthetic and sodium hyaluronate injection for the posterior disc displacement: A case report

Posterior disc displacement of the temporomandibular joint is rare. We present a unique treatment method and magnetic resonance (MR) images of this condition. The patient was a 43-year-old male with a chief complaint of abnormal occlusion. Regarding the present status, there was no occlusion on the right side. No temporomandibular joint pain, myalgia, or clicking were observed while mouth opening. On MR images, the posterior disc displacement without reduction on the right was observed and it was assumed that occlusal abnormality was due to this condition. We treated him with the following methods. After injection into the superior articular cavity with 2% lidocaine, a sodium hyaluronate preparation was injected followed by intermaxillary traction applied using rubber. The recovery of occlusion was confirmed in follow-up at 5 days after treatment. In the 13th days, the intermaxillary traction was removed. On MR images, the right disc condition was changed to anterior disc displacement with reduction. We consider our treatment methods are effective for this clinical condition.

TREATMENT OF RAT HEPATOMA BY LOCALLY INJECTION OF MURINE IL-12 RETROVIRUS PACKAGING CELL

Objective: To investigate the therapeutic effects of the murine IL-12 (mIL-12) retrovirus packaging cell line on hepatoma injected locally. Methods: The retrovirus vector encoding mIL-12 gene was constructed and transfected into packaging cell line PA317. The cells were then used to treat the rats with experimental orthotopic hepatoma at different time. The therapeutic effects, immune functions of the hosts, pathological and toxicological responses were documented. Results: the results showed that the mIL-12 retrovirus packaging cell line could significantly inhibit the growth of the hepatoma cells injected locally to the hepatoma. The early treatment made the rats survive long, while the medium or late stage treatment could prolong the life time of the rats compared with the bland control group or bland vector control group, though the rats did not survive. The number of NK cells and T cells increased significantly in the treatment group. The effects of the early treatment were superior to those of the medium and late stage treatment. Moreover, the transfection of IL-12 gene locally in the hepatoma tissue could make the hepatoma disappear from other liver lobe. This phenomenon demonstrated that IL-12 could activate the immune cells of the host to kill the untransfected tumor cells. This is very important for IL-12 to be used in gene therapy clinically. Meanwhile, the hepatoma would not recur in the rats that had survived more than 2 months from the early treatment after being re-challenged with tumor cells. Conclusion: the results showed that IL-12 gene injected locally in the hepatoma tissue could enhance the anti-tumor immunity of the host.

Effects of Repeated Injection of Local Anesthetic on Sciatic Nerve Blocks Response

In order to examine whether repeated sciatic nerve blocks showed tachyphylaxis and continuity of sciatic nerve with spinal cord affected development of tachyphylaxis when assayed in vivo by duration of depression compound action potentials (CAP), rats were anesthetized with halothane, ventilated, monitored and supported with stable hemodynamics and temperature. Posterior tibial nerve distally and sciatic nerve in thigh were exposed, placed on bipolar silver electrodes for stimulation and recording respectively. Three sequential sciatic nerve blocks were performed between these electrodes using 0.15 ml of 3 % chloroprocaine. Nine rats were chosen to observe the effects of repeated sciatic nerve blocks on CAP. In another 18 rats, a second investigator exposed the sciatic nerve near its origin at spinal cord and randomly performed nerve cut and sham (n=9), and closed the incision blinding the electrophysiologic investigator. The results showed that electrical stimulated tibial nerve induced sciatic nerve Aα/β, Aδ, C fiber mediated CAP waves. CAP amplitudes were remained stable during whole experimental procedure. CAP amplitudes were decreased completely with 3% chloroprocaine blocked sciatic nerve and recovered fully. The duration of CAP depression were reduced with repeated blocks. There were no selective blocked effects on Aα/β, Aδ, C fiber mediated CAP. With sciatic nerve cut proximally, there was no statistical significant tachyphylaxis with 3 % chloroprocaine repeated blocked sciatic nerve, and the duration of first and third blocked Aδ fiber mediated CAP was 108±20 and 92±14 min respectively (P>0.05). In normal rats the duration of first and third blocked Aδ fiber mediated CAP was 110±20 and 75±16 min respectively (P<0.05). It was suggested that tachyphylaxis to local anesthetics can occur in rats repeated blocked sciatic nerve when assayed in vivo by duration of depression CAP. The continuity of sciatic nerve with spinal cord is one of the important factors affecting the development of tachyphylaxis.

Comparison of the Effects of Kinesio Taping to Local Injection of Methyl Prednisolone in Treating Brachial Biceps Tendonitis

Objectives: This study compared the effect of Kinesio Taping (KT) with local Methyl Prednisolone injection in patients with biceps tendonitis based on visual analog scale (VAS) and range of motion (ROM). Methods: Thirty-eight patients (15 females and 23 males;mean age: 29.87 ± 6.31, years) with biceps tendonitis were participated in this study during 2014-2015. The patients were randomly assigned into two groups: 19 patients in KT group and 19 patients in injection group. In the first group, KT was used three times for 24 hours sequentially with four-day intervals;in the second group, one dose of Methyl Prednisolone (40 mg) plus 1% lidocaine was injected in the bicipital fissure around the long head of the biceps muscle. The injections and KT therapy were performed by the same physician. The patients were investigated for VAS and ROM in the first, second, seventh and twelfth days. Results: VAS and ROM indices were significantly improved in the second and seventh days (p 0.05). Conclusion: Regarding the more immediate effect of KT on ROM and VAS and the fast restoring of the patient to normal life, it could be used as a noninvasive alternative to injection and as the first line of treatment specially in patients who need the immediate effect of treatment.

Permanent Magnet Temperature Estimation for PMSMs Using Virtual Position-offset Injection

This paper proposes a virtual position-offset injection based permanent magnet temperature estimation approach for permanent magnet synchronous machines(PMSMs). The concept of virtual position-offset injection is mathematically transforming the machine model to a virtual frame with a position-offset. The virtual frame temperature estimation model is derived to calculate the permanent magnet temperature(PMT) directly from the measurements with computation efficiency. The estimation model involves a combined inductance term, which can simplify the establishment of saturation compensation model with less measurements. Moreover, resistance and inverter distorted terms are cancelled in the estimation model, which can improve the robustness to the winding temperature rise and inverter distortion. The proposed approach can achieve simplified computation in temperature estimation and reduced memory usage in saturation compensation. While existing model-based approaches could be affected by either the need of resistance and inverter information or complex saturation compensation. Experiments are conducted on the test machine to verify the proposed approach under various operating conditions.

A study of the effect of local scour on the flow field near the spur dike

The flow field near a spur dike such as down flow and horseshoe vortex system(HVS)are susceptible to the topographic changes in the local scouring process,resulting in variation of the sediment transport with time.In this study,large eddy simulations with fixed-bed at different scouring stages were conducted to investigate the changes in flow field.The results imply that the bed deformation leads to an increase in flow rate per unit area,which represent the capability of sediment transportation by water,in the scour hole.Moreover,the intensity of turbulent kinetic energy and bimodal motion near the sand bed induced by the HVS were also varied.However,the peak moments between the two sediment transport mechanisms were different.Hence,understanding the complex feedback mechanism between topography and flow field is essential for the local scour problem.

Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

Cross-upgrading of biomass hydrothermal carbonization and pyrolysis for high quality blast furnace injection fuel production:Physicochemical characteristics and gasification kinetics analysis

The paper proposes a biomass cross-upgrading process that combines hydrothermal carbonization and pyrolysis to produce high-quality blast furnace injection fuel.The results showed that after upgrading,the volatile content of biochar ranged from 16.19%to 45.35%,and the alkali metal content,ash content,and specific surface area were significantly reduced.The optimal route for biochar pro-duction is hydrothermal carbonization-pyrolysis(P-HC),resulting in biochar with a higher calorific value,C=C structure,and increased graphitization degree.The apparent activation energy(E)of the sample ranges from 199.1 to 324.8 kJ/mol,with P-HC having an E of 277.8 kJ/mol,lower than that of raw biomass,primary biochar,and anthracite.This makes P-HC more suitable for blast furnace injection fuel.Additionally,the paper proposes a path for P-HC injection in blast furnaces and calculates potential environmental benefits.P-HC of-fers the highest potential for carbon emission reduction,capable of reducing emissions by 96.04 kg/t when replacing 40wt%coal injec-tion.