Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Objective To explore the influencing factors of visual acuity recovery in patients with high myopia after posterior chamber phakic intraocular lens(ICL)implantation.Methods A prospective study was conducted on 210 pa-tients(420 eyes)with high myopia who underwent ICL implantation at the Second Affiliated Hospital of Zhengzhou Univer-sity from May 2021 to March 2023.The patients were divided into a good recovery group[best corrected visual acuity(BC-VA)recovery ≥0.3 D]and a poor recovery group(BCVA recovery＜0.3 D)based on their visual acuity recovery status three months after surgery.The baseline data of patients in the two groups were compared,and the factors affecting visual acuity recovery were analyzed using Logistic regression.The receiver operating characteristic(ROC)curve was used to an-alyze the predictive value of the Logistic regression model for poor visual acuity recovery in patients with high myopia after ICL implantation.Results Three months after surgery,149 patients(298 eyes)were in the good recovery group,and 61 patients(122 eyes)were in the poor recovery group.There were no significant differences in gender,age,years of myopi-a,body mass index,and academic performance between the two groups(all P＞0.05).The proportions of patients with corneal astigmatism＜1.30 D(55.74％),corneal diopter＜45 D(59.02％),Pittsburgh Sleep Quality Index(PSQI)＜7 points(63.93％),and average central radius of curvature[(7.82±0.27)mm]in the poor recovery group were lower than those in the good recovery group[83.89％,81.88％,85.91％,and(7.90±0.24)mm,respectively].The central flat me-ridian curvature(k1)of the anterior corneal surface[(43.27±1.43)D],steep meridian curvature(k2)of the anterior corneal surface[(44.84±1.53)D],and arch height[(628.49±67.28)μm]in the poor recovery group were higher than those in the good recovery group[(42.73±1.42)D,(44.12±1.47)D],and[(417.56±80.14)pm],with significant differences(all P＜0.05).Logistic regression analysis showed that corneal astigmatism,corneal diopter,k1,k2,arch height,and PSQI score were independent influencing factors of poor visual acuity recovery after ICL implantation in pa-tients with high myopia(all P＜0.05).ROC curve analysis showed that the area under the ROC curve for predicting poor visual acuity recovery after ICL implantation in patients with high myopia by Logistic regression model was 0.938(95％CI:0.896-0.966),the sensitivity was 83.61％,and the specificity was 91.95％(P＜0.05).Conclusion The visual acuity recovery after ICL implantation in patients with high myopia is affected by corneal astigmatism,corneal diopter,k1,k2,arch height,and PSQI score.The Logistic regression model based on these factors has high predictive value for visual acui-ty recovery after ICL implantation.

OBJECTIVE To observe the clinical efficacy of Erdong Xiaoke Formula in the treatment of type 2 diabetes dry eyes with yin deficiency and heat excess syndrome and its effect on serum interleukin 17(IL-17)and interleukin 1β(IL-1β),and to ex-plore the therapeutic mechanism of Erdong Xiaoke Formula.METHODS 110 cases of type 2 diabetes patients with dry eyes of yin deficiency and heat excess syndrome from Jiangsu Province Hospital of Chinese Medicine were enrolled and randomly divided into a treatment group and a control group,55 cases each.5 cases dropped out of the treatment group and 4 cases dropped out of the control group.The control group was given a basic hypoglycemic regimen combined with topical sodium hyaluronate eye drops.The treatment group was given Erdong Xiaoke Formula in addition to the treatment in the control group.The treatment course for both groups was 4 weeks.Changes in TCM syndrome scores of the two groups of patients were observed before and after treatment,and the clinical effica-cy of TCM was evaluated.Blood glucose and pancreatic islet function-related indicators[fasting blood glucose(FBG),fasting insulin(FINS),fasting C-peptide(FCP),postprandial 2 h blood glucose(PBG),insulin secretion function index(HOMA-β),insulin re-sistance index(HOMA)-IR)],ocular surface indicators[tear break up time(BUT),corneal sodium fluorescein staining(FL),Schirmer Ⅰ test(SⅠT)],and inflammation-related indicators(IL-17,IL-1β)were detected.The occurrence of adverse reactions in the two groups of patients was observed during the treatment period.RESULTS After treatment,the total scores of TCM syn-dromes in both groups were significantly reduced(P＜0.01),the treatment group was better than the control group(P＜0.01),and the total effective rate of TCM syndromes in the treatment group was higher than that of the control group(P＜0.01);SⅠT and BUT of pa-tients in both groups increased significantly(P＜0.01),and the treatment group was better than the control group(P＜0.05,P＜0.01);the FL of patients in both groups significantly reduced(P＜0.01),and there was no significant difference between the groups;the ser-um IL-17 and IL-1β of the patients in the treatment group decreased significantly(P＜0.01),which was significantly better than that of the control group(P＜0.05).There were no significant changes in blood glucose and pancreatic islet function-related indicators in the two groups before and after treatment(P＞0.05).During the treatment,no obvious adverse reactions were observed in the two groups.CONCLUSION Erdong Xiaoke Formula can improve SⅠT,BUT,FL and eye symptoms in patients with diabetic dry eye,effectively treat diabetic dry eye,and reduce ocular surface inflammation.Its mechanism may be related to reducing serum inflammato-ry factors IL-17 and IL-1β.

Objective:To evaluate the relationship between glutathione S-transferase μ1 (GSTM1) and the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling pathway during therapeutic hypothermia-induced reduction of cerebral ischemia-reperfusion injury (CIRI) in rats.Methods:One hundred clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 5 groups ( n=20 each) using a random number table method: sham operation group (S group), cerebral ischemia-reperfusion group (I/R group), therapeutic hypothermia group (H group), GSTM1 inhibitor+ therapeutic hypothermia group (IH group), and GSTM1 inhibitor + ASK1 inhibitor + therapeutic hypothermia group (IAH group). CIRI model was developed by occlusion of the left middle cerebral artery for 2 h, followed by restoration of the blood flow. A nylon thread was inserted into the internal carotid artery and advanced cephalad until resistance was met. The brain temperature was maintained at 36-37 ℃ during surgery. In H group, the head and neck were wiped with 75% alcohol immediately after reperfusion, and the brain temperature was maintained at 32-33℃ for 3 h, and the rest procedures were the same as those previously described in I/R group. In IH group, GSTM1 inhibitor itaconic acid 8.6 mg/kg was intraperitoneally injected at 24 and 1 h before developing the model, and the rest procedures were the same as those previously described in H group. In IAH group, ASK1 inhibitor selonsertib 10 mg/kg was given orally once a day for 4 consecutive days starting from 4 days before developing the model, and the rest procedures were the same as those previously described in IH group. Modified Neurological Severity Score (mNSS) was assessed at 24 h of reperfusion, then the rats were sacrificed and brains were harvested for microscopic examination of brain infarction, neuronal morphology (using HE staining) and for determination of the expression of GSTM1, ASK1, phosphorylated ASK1 (p-ASK1), JNK, phosphorylated JNK (p-JNK), p-38 MAPK and phosphorylated p-38 MAPK (p-p38 MAPK) (by Western blot) and neuronal apoptosis (by TUNEL assay). The percentage of the infarct size was calculated using TTC staining. The apoptosis rate was calculated. Results:Compared with S group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly increased, and the expression of GSTM1 was down-regulated in I/R group ( P<0.05). Compared with I/R group and IH group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly decreased, the expression of GSTM1 was up-regulated ( P<0.05), and the neuronal injury was significantly attenuated in H group. Compared with IH group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly decreased ( P<0.05), no significant change was found in GSTM1 expression ( P>0.05), and the neuronal damage was significantly attenuated in IAH group. Conclusions:The mechanism by which therapeutic hypothermia alleviates CIRI is related to up-regulating the expression of GSTM1 and inhibiting the activation of the ASK1-JNK-p38 MAPK signaling pathway in rats.

Non-invasive mechanical ventilation(NIV)is increasingly being used as a respiratory support technique in clinical practice.However,the pressure-related injuries should not be overlooked.In order to prevent local pressure injuries caused by NIV technology,a series of preventive measures have been adopted in clinical work.These measures include the use of dressings to provide pressure relief to the local skin.Currently,in clinical practice,when using preventive dressings,nurses need to cut them themselves based on the physiological structure of the patient's nose,forehead,or face.However,precise cutting can be challenging.If the dressing is cut too small,it may not provide adequate prevention,and if it's cut too large,it can cover too much skin,affecting the nurse's observation and the patient's comfort.Additionally,during NIV treatment,the preventive dressings used may become curled or displaced,requiring nurses to re-cut and replace them.This process inevitably leads to material wastage,increasing the cost of dressing use for patients.Moreover,the cutting tools used must meet infection control requirements,adding to the nursing workload and reducing the compliance of nurses in changing dressings.Our research team has designed a ready-made pressure injury prevention dressing component for use with NIV masks to prevent pressure injuries to the nasal and facial areas.It is precisely designed,flexible in composition,easy to use,and can provide multiple usage modes.It effectively combines emergency care with pressure relief measures,reducing the occurrence of pressure injuries to the patient's nasal and facial areas.This improves patient comfort and treatment compliance,facilitates technology-based nursing,and enhances clinical efficiency.It has significant clinical application value and has been granted a National Utility Model Patent(ZL 202020529121.6).

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Objective:To evaluate the role of glutathione S-transferase μ1 (GSTM1) expression in mild hypothermia-induced mitigation of cerebral ischemia-reperfusion (I/R) injury and the relationship with microglial polarization.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (S group), cerebral I/R group (I/R group), mild hypothermia group (H group), and GSTM1 inhibitor + mild hypothermia group (IH group). The rat model of cerebral I/R injury was prepared using the filament occlusion method. The filament was removed to restore blood flow after the left middle cerebral artery was blocked for 2 h, and the rats′ brain and rectal temperature were maintained at 36-37 ℃ during the period. The vessels were only isolated and ligated without occlusion in S group. In H group, the entire body was wiped with 75% ethanol immediately after removing the filament, and the brain and rectal temperatures were maintained at 32-33 ℃ for 3 h, and the other procedures were the same as those previously described in I/R group. In IH group, GSTM1 inhibitor itaconic acid 8.6 mg/kg was intraperitoneally injected at 24 and 1 h before developing the model, and the other procedures were the same as those previously described in H group. Neurological deficits were evaluated using a modified neurological severity score (mNSS) at 24 h of reperfusion, and then the animals were sacrificed and the brains were removed for observation of cerebral infarction (by TTC staining) and for determination of the expression of GSTM1, M1-type microglial marker inducible nitric oxide synthase (iNOS), and M2-type microglial marker arginase-1 (Arg-1) (by Western blot), expression of GSTM1, iNOS and Arg-1 mRNA (quantitative real-time polymerase chain reaction) and contents of interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) (by enzyme-linked immunosorbent assay). Results:Compared with S group, the mNSS and percentage of cerebral infarct size were significantly increased, and the expression of iNOS and Arg-1 protein and mRNA was up-regulated, the expression of GSTM1 and mRNA was down-regulated, and the contents of IL-6, TNF-α, IL-10 and TGF-β were increased in the other three groups ( P<0.05). Compared with I/R group and IH group, the mNSS and percentage of cerebral infarct size were significantly decreased, and the expression of iNOS protein and mRNA was down-regulated, the expression of Arg-1 protein and mRNA and GSTM1 was up-regulated, the contents of TNF-α and IL-6 were decreased, and the contents of TGF-β and IL-10 were increased in H group ( P<0.05). Conclusions:Up-regulated expression of GSTM1 is involved in mild hypothermia-induced mitigation of cerebral I/R injury, which is associated with inhibition of microglial polarization toward the M1 phenotype and promotion of polarization toward the M2 phenotype.

Objective:To evaluate the relationship between hippocampal miR-3065-5p and insulin-like growth factor-1/phosphatidylinositol 3-kinase/protein kinase B(IGF-1/PI3K/Akt)signaling pathway in a mouse model of perioperative neurocognitive disorder (PND).Methods:Eighty clean-grade healthy male C75BL/6 mice, aged 12-14 weeks, weighing 20-30 g, were divided them into 4 groups ( n=20 each) using the random number table method: control group (C group), PND group, miR-3065-5p agonist group (Ag group) and miR-3065-5p agonist negative control group (Ag-NC group). PND model was prepared by internal fixation of tibial fracture under anesthesia with 1.5% isoflurane. Two days before developing the model, miR-3065-5p agomir 2 μl was injected into the lateral ventricle in Ag group, miR-3065-5p agomir negative control 2 μl was injected into the lateral ventricle in Ag-NC group. Morris water maze test and open field test were performed at 7 days after surgery. The mice were sacrificed after the end of test, and hippocampal tissues were obtained for determination of the expression of miR-3065-5p, IGF-1 mRNA and Bcl-2 mRNA (by quantitative real-time polymerase chain reaction) and expression of IGF-1, phosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase-3β (p-GSK3β) and Bcl-2 (by Western blot). Results:There was no significant difference in each parameter in the open field test among the four groups ( P>0.05). Compared with group C, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in the other three groups ( P<0.05). Compared with PND group and Ag-NC group, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in Ag group ( P<0.05). Conclusions:Up-regulation of miR-3065-5p can inhibit the activation of IGF-1/PI3K/Akt signaling pathway, which might be one of the mechanisms of PND developed in mice.

Objective:To investigate the effects of mild hypothermia on microglia polarization and janus kinase 2/signal transduction and transcriptional activation factor 3 (JAK2/STAT3) signaling pathway during cerebral ischemia-reperfusion (I/R) in rats.Methods:Forty-five clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 3 groups ( n=15 each) by the random number table method: sham operation group (S group), cerebral I/R group (I/R) and mild hypothermia group (H group). In I/R group and H group, cerebral I/R was induced by middle cerebral artery occlusion using a nylon thread in anesthetized animals, the nylon thread was removed to restore the perfusion after 2 h of occlusion, and the rectal temperature was maintained at 36-37 ℃ during the period. Group H was wiped with 75% alcohol for 3 h starting from the time point immediately after reperfusion, and the rectal temperature was maintained at 32-33℃. Modified neurological severity score (mNSS) was evaluated at 24 h of reperfusion. Animals were then sacrificed for determination of the cerebral infarct size (using TTC staining), expression of M1 marker inducible nitric oxide synthase (iNOS), M2 marker arginase 1(Arg-1), phosphorylated JAK2(p-JAK2)and phosphorylated STAT3(p-STAT3)(by Western blot), expression of iNOS mRNA and Arg-1 mRNA (by quantitative polymerase chain reaction), and contents of interleukin-6 (IL-6) and IL-10 (by enzyme-linked immunosorbent assay). Results:Compared with group S, mNSS and cerebral infarct size were significantly increased, the expression of iNOS, Arg-1 protein and mRNA in cerebral ischemic penumbral zone was up-regulated, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio, and contents of IL-6 and IL-10 were increased in the other two groups ( P<0.05). Compared with I/R group, mNSS and cerebral infarct size were significantly decreased, the expression of iNOS protein and mRNA in cerebral ischemic penumbral zone was down-regulated, the expression of Arg-1 and mRNA was up-regulated, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and IL-6 content were decreased, and the IL-10 content was increased in group H ( P<0.05). Conclusions:Mild hypothermia can promote the polarization shift of microglia from M1 to M2 phenotype during cerebral I/R and inhibit the central inflammatory responses, and the mechanism may be related to inhibition of JAK2/STAT3 signaling pathway in rats.

This study comprehensively analyzes the course of Military Medical Psychology from 7 aspects including the nature and status, teaching objectives, teaching principles, teaching concepts, classroom teaching, practical teaching and lecturing principles, and finally summarizes the characteristics of the course and points out its shortcomings and prospects. The study found that the Military Medical Psychology is an important interdisciplinary course between medical psychology and military science; the teaching objectives include two categories, the overall goals and classified ones; the teaching principle emphasizes the forces of developing practice ability of service orientation; the teaching concept includes combining the theory with practice, focusing on the students, informatization and lectures; the mode of classroom teaching should be cases-introduction, theory-interpretation and case-analysis; the practical teaching should strengthen teaching skills, emphasize connection, stimulate interest and improve the health; lecturing principles emphasize the focus of content. This study has preliminarily completed the teaching design of the course of Military Medical Psychology, which is conducive to the smooth implementation of this course and the cultivation of professional talents of military medical universities.