Objective To evaluate the apparent diffusion coefficient(ADC)values of different bone marrow infiltration patterns in multiple myeloma(MM)patients with MR whole-body diffusion weighted imaging(WB-DWI)and to determine the ADC thresholds for different bone marrow infiltration patterns.Methods Nineteen MM patients diagnosed for the first time were selected.The lesions types of each site(cervical spine,ribs,sternum,humerus,scapula,sacral spine,ilium,femur,thoracic spine,and lumbar spine)after the WB-DWI images were visually evaluated,which were divided into focal group(including focal lesion in combined focal and diffuse infiltration)[region of interest(ROI)=141],pure diffuse infiltration group(ROI=150),diffuse lesion in combined focal and diffuse infiltration group(ROI=127),"salt-and-pepper"group(ROI=54),and normal appearance group(ROI=68).ADC values were measured and compared between each group and the receiver operating characteristic(ROC)curve was drawn to distinguish different patterns of bone marrow infiltration.Results There was no statistically significant difference in ADC values between the diffuse lesion in combined focal and diffuse infiltration group and the"salt-and-pepper"group(P＞0.99),and there was statistically significant difference in ADC values between the other groups(P＜0.05).The ROC curve showed that the area under the curve(AUC)for identifying focal group and the"salt-and-pepper"group was 0.889[95％confidence interval(CI)0.844-0.934],the AUC for identifying pure diffuse infiltration group and the normal appearance group was 0.968(95％CI 0.949-0.987).ADC values were able to accurately and visually differentiate between the different patterns of bone marrow infiltration.Conclusion The ADC values can be used as a quantitative tool to objectively distinguish different bone marrow infiltration patterns in MM patients.

Objective To observe the effect of quercetin on mechanical allodynia,astrocyte activation,and upregulation of pain-related transient receptor potential vanilloid 1(TRPV1)and P2X purinoceptor 3(P2X3)in mice with paclitaxel-induced peripheral neuropathy.Methods Twenty-four C57BL/6 mice were divided randomly into control,model,and model+quercetin groups(n=8 mice per group).Paclitaxel(total dose 8 mg/kg)was injected intraperitoneally into mice in the model and model+quercetin groups to establish the model.Mice in the control group were injected intraperitoneally with the same volume of vehicle.On day 8 after the first injection,mice in the model+quercetin group were injected with 60 mg/kg quercetin solution orally and mice in the other groups were injected with the same volume of vehicle.Mechanical pain was measured by the von Frey test.Activation of astrocytes in the spinal dorsal horn was detected by immunofluorescence.Expression levels of TRPV1 and P2X3 in dorsal root ganglia were detected by immunofluorescence and Western Blot.Results(1)Compared with model group,the mechanical pain of mice in model+quercetin group were relieved.(2)Compared with model group,the activation of astrocytes and the expressions of TRPV1 and P2X3 in mice of model+quercetin group were alleviated(P＜0.05).Conclusions Quercetin can significantly reduce mechanical pain in mice with paclitaxel-induced peripheral neuropathy.This mechanism maybe related to alleviating the activation of astrocytes in the spinal dorsal horn and reducing expression of TRPV1 and P2X3 in the dorsal root ganglia.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10^-15 g/L, and the quantitative limit reached 1.0 × 10^-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (K_D) of 5.701 × 10^-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a K_D of up to 4.181 × 10^-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1^Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Ferroptosis

Objective:To analyze the risk factors of postinflammatory hyperpigmentation (PIH) after laser in the treatment of acquired bilateral nevus of Ota-like macules (ABNOM).Methods:A retrospective study was conducted to follow up 120 patients with acquired bilateral nevus of Ota-like macules in the Department of Laser and Physiotherapy, Guangzhou Institute of Dermatology between January 2011 and December 2018, which accepted 1064-nm Q-switched neodymium: yttrium-aluminum-garnet laser treatment. The difference was analyzed between different age, sex, clinical classification, Fitzpatrick skin classification, ABNOM with melasma and postinflammatory pigmentation after laser treatment. Logistic regression was used to analyze the risk factors of postinflammatory hyperpigmentation after 1064-nm Q-switched neodymium: yttrium-aluminum-garnet laser treatment of acquired bilateral nevus of Ota-like macules.Results:Fifty-three ABNOM patients (44.17%) developed PIH after laser treatment. Univariate analysis showed that age, clinical classification, Fitzpatrick skin classification and the patients with both ABNOM and melasma all affected the occurrence of PIH after laser in the treatment of ABNOM, and the difference was statistically significant ( P<0.01). Logistic regression showed that older age, more severe clinical classification and the presence of ABNOM with melasma were the risk factors of PIH after treatment of ABNOM. Conclusions:ABNOM patients should be treated as early as possible. The risk of inducing PIH is great after laser treatment in patients with more severe clinical classification and patients with both ABNOM and melasma.

The cystine/glutamate antiporter SLC7A11 (also commonly known as xCT) functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers. Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis, a form of regulated cell death induced by excessive lipid peroxidation. However, cancer cells with high expression of SLC7A11 (SLC7A11

Ferroptosis, an iron-dependent form of regulated cell death driven by peroxidative damages of polyunsaturated-fatty-acid-containing phospholipids in cellular membranes, has recently been revealed to play an important role in radiotherapy-induced cell death and tumor suppression, and to mediate the synergy between radiotherapy and immunotherapy. In this review, we summarize known as well as putative mechanisms underlying the crosstalk between radiotherapy and ferroptosis, discuss the interactions between ferroptosis and other forms of regulated cell death induced by radiotherapy, and explore combination therapeutic strategies targeting ferroptosis in radiotherapy and immunotherapy. This review will provide important frameworks for future investigations of ferroptosis in cancer therapy.
Ferroptosis/immunology* ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Radiotherapy

Objective: To evaluate the rationality and effectiveness of basic laparoscopic training under 5A teaching mode. Methods: A prospective randomized controlled study was conducted. The teaching records of 70 trainees who received basic laparoscopic traning at the Laparoscopic Surgical Training Base in Chinese PLA General Hospital from July to December 2019 were analyzed. All the trainees participating in the laparoscopy training had obtained the national practicing physician certificates, including 12 junior physicians of our center, 9 intermediate physicians of our center, 19 advanced physicians, 13 postgraduate students, 8 doctoral students, and 9 surgical standardized training physicians. A random number table method was used to divide all the trainees into two groups: the traditional teaching group or the 5A teaching group (35 people in each group). In the traditional teaching group, the training of 4 modules of " precise beans, quincuncial piles, ring positioning and knot-tying suture" modules according to a fixed sequence and schedule was carried out. Each module had a learning time of 8 hours. In the 5A teaching group, the training started from five dimensions of analysis, aim, accomplishment, appraise and advance. Before conducting each stage of training, the actual operation ability of the trainees was tested, each class hour was designed individually, accurate teaching was conducted to the trainees, the ability of the trainees was evaluated dynamically, and the previous steps were cycled periodically based on class hours. The operating time and pass rate of trainees of two groups in the basic operation module of laparoscopy were statistically analyzed, and a hierarchical analysis of related influencing factors was conducted. Results: The time of above modules before training in the 5A teaching group and the traditional teaching group was similar (all P>0.05). After definitive training, the time required for trainees in 5A teaching group and traditional teaching group to complete the 4 modules was shortened to varying degrees. Compared to traditional teaching group, 5A teaching group spent less time in completing each project [precise beans: (63.2±10.1) seconds vs. (83.6±18.7) seconds, quincuncial piles: (56.2±7.3) seconds vs. (101.4±31.7) seconds, ring positioning: (84.2±13.7) seconds vs. (127.3±28.5) seconds, knot-tying suture: (263.2±41.8) seconds vs.(428.8±95.2) seconds, all P<0.05], and had higher pass rates [precise beans: 97.1% (34/35) vs. 80.0% (28/35), quincuncial piles: 91.4% (32/35) vs.71.4% (25/35), ring positioning: 100.0% (35/35) vs. 82.9% (29/35), knot-tying suture: 77.1% (27/35) vs. 60.0% (21/35), all P<0.05]. Among the junior trainees (junior physicians of our center, postgraduate students, doctoral students, and standardized surgical training physicians) and intermediate trainees (intermediate physicians of our center and advanced physicians), the 5A teaching group completed 3 modules (quincuncial piles, ring positioning and knot-tying suture) faster than the traditional teaching group [junior trainees: quincuncial piles (76.4±12.4) seconds vs. (139.8±41.6) seconds, ring positioning (92.2±20.5) seconds vs. (131.3±28.4) seconds, knot-tying suture (293.8±66.7) seconds vs. (444.3±103.3) seconds; intermediate trainees: quincuncial piles (51.4±5.9) seconds vs. (94.7±8.6) seconds, ring positioning (63.9±13.5) seconds vs. (87.5±18.6) seconds, knot-tying suture (210.1±35.6) seconds vs. (367.5±54.9) seconds, all P<0.05]. Conclusion: 5A teaching mode can acheive better training results compared with the traditional teaching mode in basic laparoscopic training, and is worthy of further popularization and application.
Clinical Competence ; Humans ; Laparoscopy ; Prospective Studies ; Suture Techniques ; Sutures