As an emerging drug delivery technology,microneedles can puncture the skin's stratum corneum to create micron-sized conduits,painlessly,minimally invasive,and efficiently deliver drugs into viable epidermis or dermis for local or systemic therapeutic effects.This paper reviews the current clinical trials of microneedles used in the treatment of various diseases,elaborates on the characteristics of various types of microneedles,and summarizes the latest research progress of microneedles used to treat skin tumors,including chemotherapy,photothermal and photodynamic therapy,immunotherapy,gene therapy,and combination therapy.This review provides ideas and directions for further research on microneedles in treating skin tumors.

Objective: To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis (KOA) model. Methods: Rabbits (n = 18) were randomly divided into control, KOA, and KOA + acupotomy (Apo) groups (n = 6). The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks. After modeling, the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis, vastus lateralis, rectus femoris, biceps femoris, and anserine bursa tendons around the knee. The behavior of all animals was recorded, rectus femoris tissue was obtained, and histomorphological changes were observed using Masson staining and transmission electron microscopy. The expression of transforming growth factor-β1 (TGF-β1), Smad 3, Smad 7, fibrillar collagen types I (Col-I) and III (Col-III) was detected using Western blot and real-time polymerase chain reaction (RT-PCR). Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris, compared with the KOA group (P = .034). Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA, thus preventing skeletal muscle fibrosis. Western blot and RT-PCR analysis revealed that in the Apo group, Col-I, and Col-III protein levels were significantly lower than those in the KOA group (both P < .01), same as Col-I and Col-III mRNA levels (P = .0031; P = .0046). Compared with the KOA group, the protein levels of TGF-β1 and Smad 3 were significantly reduced (both P < .01), as were the mRNA levels of TGF-β1 and Smad 3 (P = .0007; P = .0011). Conversely, the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group (P < .01; P = .0271). Conclusion Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals ; Mice ; Dark Adaptation ; Light ; Retina ; Retinal Cone Photoreceptor Cells/metabolism* ; Adaptation, Ocular ; Neuroglia/physiology* ; Cell Communication ; Thyroid Hormones

Objective:To explore the short-term efficacy and safety for the new adjuvant therapy of programmed cell protein-1(PD-1)inhibitor combined with Oxaliplatin+Tegafur(SOX)in locally advanced gastric adenocarcinoma. Methods:Retrospective collection of clinical data from 72 locally advanced(stage Ⅲ)gastric adenocarcinoma patients admitted to our gastrointestinal surgery department from January 2020 to July 2020,according to different treatment plans,patients were divided into a control group(n=36)and an observation group(n=36).The control group received SOX chemotherapy regimen,while the observation group received PD-1 inhibitor combined with SOX regimen.Both groups of patients underwent chemotherapy for 3 cycles,and were re-evaluated after resting for 3-4 weeks.Patients with no disease progression and tolerable surgery underwent D2 gastric cancer radical surgery.The overall survival(OS),pathological complete response(pCR)rate,progression free survival period(PFS),RO resection rate,objective response rate(ORR),disease control rate(DCR)and adverse drug reaction were compared between the two groups. Results:The pCR rate,ORR and DCR of the observation group were significantly higher than those of the control group[pCR rate:25％(9/36)vs 5.6％(2/36),x2=5.258,P=0.022;ORR:58.33％(21/36)vs 25.00％(9/36),x2=8.229,P=0.004;DCR:88.89％(32/36)vs 69.44％(25/36),x2=4.1 26,P=0.042].The incidence of adverse reactions such as elevated ALT,elevated AST,and hand foot syndrome during neoadjuvant chemotherapy in the observation group was significantly higher than those in the control group(P＜0.05).The incidence of other adverse reactions was not significantly difference between the two groups of patients(P＞0.05),and there were no neoadjuvant chemotherapy related death events in both groups.The R0 resection rates of the two groups were 97.22％and 91.67％,respectively(x2=1.059,P=0.303).The median OS and median PFS of 72 patients were 36 and 1 3 months,respectively.The 2-year OS rate of the two groups were 82.2％and 71.5％,respectively.Kaplan Meier survival curve analysis showed that the OS rate of the observation group was significantly higher than that of the control group(x2=4.240,P=0.039);the median PFS of the observation group was higher than that of the control group at 14 and 1 1 months,respectively(x2=4.173,P=0.041);COX univariate regression analysis did not identify any factors affecting survival of locally advanced gastric adenocarcinoma. Conclusion:The neoadjuvant treatment of locally advanced gastric adenocarcinoma with PD-1 inhibitor combined with SOX regimen is safe and effective,and the adverse reactions are controllable.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective:To investigate the expression and significance of T helper cell 17 (Th17), soluble intercellular adhesion molecule-1 (sICAM-1) and coagulation function in patients with infectious endocarditis(IE).Methods:From December 2016 to December 2018, IE patients in Beijing Anzhen Hospital Affiliated to Capital Medical University who met the inclusion criteria were selected for cardiac surgery to analyze prospectively, 38 IE patients were selected as the observation group, and 30 healthy people were selected as the control group.The concentrations of serum Th17 related factors (IL-1β, IL-6, IL-17 and IL-21), sICAM-1 and coagulation index(P selectin(sP-SLT)) were measured by enzyme-linked immunosorbent assay(ELISA) and the difference between the two groups were statistically analyzed.Results:The concentrations of serum IL-1β, IL-6, IL-17 and IL-21((29.88±6.49), (14.89±3.31), (21.89±3.01), (563.26±67.36) ng/L) in the observation group were significantly higher than those in the control group((16.56±4.11), (7.52±2.34), (12.91±1.01), (423.38±56.49) ng/L)(all P<0.05). The level of serum sICAM-1 and sP-SLT ((1 247.57(581.39, 1 794.66) μg/L, (60.29±6.61) mg/L)in the observation group were significantly higher than those in the control group((837.28(405.68, 954.47) μg/L, (27.37±5.56) mg/L), and the difference was statistically significant( Z=12.37, t=22.30, all P<0.05). The level of serum IL-1β, IL-6, IL-17 and IL-21 in patients with postoperative infective endocarditis((16.19±4.07), (7.73±2.40), (13.83±0.94), (425.33±52.12) ng/L) were significantly lower than those before operation((29.88±6.49), (14.89±2.31), (21.89±3.01), (563.26±67.36) ng/L), and the differences were statistically significant(t values were 11.02, 13.25, 15.76, 9.98, all P<0.05). The levels of sICAM-1 and sP-SLT1 in patients with postoperative infective endocarditis((901.46(472.15, 1276.58) μg/L, (30.70±5.31) mg/L) were significantly lower than those before operation((1 057.26±463.06) μg/L, (60.29±6.61) mg/L)and the differences were statistically significant( Z=11.16, t=21.51, P<0.05). Conclusion:Th17 related factors, sICAM-1 and sP-SLT were highly expressed in IE patients, and the concentrations of these factors decreased after operation, suggesting that the above factors may be used as related factors for the diagnosis and prognosis of IE patients.

Chronic pain is a worldwide public health problem in which neuropathic pain (NP) caused by nerve damage is the most common chronic pain. At present, NP lacks effective treatment for any reason. In recent years, increasing studies have shown that neuroimmunity and neuroinflammation play a key role in mediating NP, and nuclear factor-kappa B (NF-κB) plays the most important role in the expression of pain inducers and effectors in the immune and inflammatory systems. NF-κB promotes transcriptional up-regulation by a promoter that links to a variety of inflammatory factors. Therefore, this paper reviews the research status of the role of NF-κB in NP.

Objective To explore the feasibility of electromagnetic navigation for hepatic ducts exploration by choledochoscope based on a three-dimensional (3D) printing model.Methods The retrospective descriptive study was conducted.The clinical data of 1 patient with obstructive jaundice combined with secondary biliary tract dilation who was admitted to the Beijing Tsinghua Changgung Hospital in April 2016 were collected.Digital imaging and standardized format data of enhanced computed tomography (CT) scan were collected,3D reconstruction of liver and bile duct were done under a 3D printing model,and then a hollow model of bile duct was achieved.Choledochoscope with internal electromagnetic probe was inserted into the printed hepatic ducts.Four points of anatomical markers in left and right hepatic ducts and common hepatic duct were chosen as fiducial markers for calibration and registration.Results After registration,the scope can be tracked in main hepatic segmental bile ducts.The locations of choledochoscope matched precisely the navigation results.Conclusion Electromagnetic navigation may bring accurate tracking effectiveness for choledochoscopic examination.

Objective To investigate the correlation of the anti-cardiolipin(aCL) antibodies and anti-β2 glycoprotein Ⅰ(anti-β2GPI) antibodies in missed abortion women.Methods Fourteen patients diagnosed missed abortion were chose as trial group,while 20 normal females received induced abortion in the same time as control group.Chemiluminescence method was used to measure the serum levels of IgG/IgM aCL and IgG/IgM anti-β2GPI antibodies in the two groups.Results The median levels of serum IgM aCL antibodies and serum IgM anti-β2GPI antibodies in trial group were significantly higher than those of control group(21.3(2.2-39.4)KU/L vs.6.0(1.5-10.7) KU/L,11.9(1.2-25.4) KU/L vs.1.9(1.1-4.0) KU/L;u=2.031,2.912;P ＜0.05).There were no significant differences in terms of the levels of serum IgG aCL antibodies and serum IgG anti-β2GPI antibodies between trial group and control group (P＞0.05).Conclusion There is correlation between IgM aCL as well as IgM anti-β2GPI antibodies and missed abortion,so in reducing the incidence of missed abortion,early and dynamic detection of anti-cardiolipin and anti-β2 glycoprotein I antibodies in childbearing women has a certain clinical significance.

OBJECTIVETo compare the safety and efficacy between three-field lymphadenectomy and normative Ivor-Lewis two-field lymphadenectomy for thoracic esophageal squamous cell carcinoma METHODS: Clinical data of 375 patients with thoracic esophageal squamous cell carcinoma who underwent three-field lymphadenectomy(3FL) or Ivor-Lewis two-field lymphadenectomy(2FL, Ivor-Lewis) in Fudan University Shanghai Cancer Center during 2013 were retrieved and collected from electronic medical record system. Ninety-one patients received three-field lymphadenectomy (3FL group), including 16 cases of intra-cervical gastro-esophageal anastomosis and 75 cases of intra-thoracic gastro-esophageal anastomosis, while 284 patients received Ivor-Lewis two-field lymphadenectomy (2FL group) with all intra-thoracic gastro-esophageal anastomosis. Short-term outcomes were compared between two groups, including postoperative anastomotic leakage, pneumonia and respiratory failure, chylothorax, reoperation and 90-day death. Total harvested lymph nodes and positive lymph nodes in each group were also compared. A total of 338 patients were enrolled into survival analysis. Survival curve was presented by Kaplan-Meier method.

RESULTSAs compared to 2FL group, the 3FL group had significantly higher ratio of N3 patients [19.8% (18/91) vs. 5.3% (15/284), P=0.000], stageIII( patients [58.2%(53/91) vs. 43.0%(122/284), P=0.007], and upper thoracic cancer patients [12.1%(11/91) vs. 3.5%(10/284), P=0.027]; also the 3FL group had more harvested lymph nodes (40.1±14.6 vs. 25.3±9.4, P=0.000) and more positive lymph nodes (3.3±4.0 vs. 1.7±3.2, P=0.000). With respect to pneumonia and respiratory failure, chylothorax, reoperation and 90-day death, no significant differences were found between the group (P=0.447, P=0.751, P=0.678, P=0.685). The 3FL group had a significantly higher incidence of anastomotic leakage than 2FL group [7.7% (7/91) vs. 1.8% (5/284), P=0.011], while its incidence of intrathoracic anastomosis leakage was 4.0% (3/75), which was not significantly different with 1.8%(5/284) of 2FL group (P=0.372). Median follow-up was 33 months. Overall 1-, 2-, 3-year survival rates were 94%, 81% and 70%, while 1-, 2-, 3-year survival rates of 3FL group were 90%, 73% and 66%, of 2FL group were 95%, 84% and 72%, respectively, without significant differences between the two group(P=0.135). Further subgroup analysis showed that no significant differences of postoperative survival in stage I(, II( and III( patients were observed between the two groups (P=0.541, P=0.511, P=0.402), meanwhile no significant differences of postoperative survival in patients with metastasis and without metastasis were found between the two groups as well (P=0.985, P=0.233).

CONCLUSIONSThree-field lymphadenectomy can be performed with acceptable perioperative morbidity and mortality. The prognosis value of three field lymphadenectomy needs further investigation. Patients with thoracic esophageal squamous cell carcinoma may have favorable survival through normative Ivor-Lewis two-field lymphadenectomy.

Anastomotic Leak ; etiology ; Antineoplastic Protocols ; Carcinoma, Squamous Cell ; mortality ; surgery ; China ; Esophageal Neoplasms ; mortality ; surgery ; Esophagectomy ; adverse effects ; methods ; mortality ; Humans ; Incidence ; Lymph Node Excision ; adverse effects ; methods ; mortality ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Survival Rate ; Thoracic Neoplasms ; mortality ; surgery ; Treatment Outcome