Immunoassays are widely used in medicine, food, environment and other fields due to having the advantages of simpleness, rapidness and accuracy. Combining immunoassays with nanomaterials can improve the performance of immunoassays. Compared with traditional nanomaterials, upconversion nanoparticles (UCNPs) have excellent optical properties such as good photostability, long luminescence lifetime and narrow and tunable emission bands, which can significantly reduce background noise and improve analytical sensitivity when combined with immunoassay. This paper briefly introduces the luminescence mechanism of UCNPs, summarizes the synthesis and surface modification methods of UCNPs. And then 5 UCNPs-based immunoassay techniques, namely, fluorescence resonance energy transfer, inner filter effect, magnetic separation technique, upconversion-linked immunosorbent assay and upconversion immunochromatography, are discussed in detail. These sensing protocols of UCNPs-based immunoassays have been successfully utilized to detect various targets, including small molecules, macromolecules, and pathogens, all of which closely related to food safety, human health, and environmental pollution. Finally, the challenges and prospects of this technique are summarized and prospected. Although the UCNPs immunoassays based on antibodies and antigens have made great progress, most of the research is still in the stage of laboratory, and there is a long way to go to realize its social applications. There is a series of challenges need to be overcome. (1) Designing excellent water soluble and dispersive upconversion nanomaterials is needed. Hydrophilic ligands are bound to smaller upconversion nanoparticles and removing hydrophobic surface ligands are the most widely used methods to improve solubility and dispersity. (2) Multi-detection technology platforms and multi-mode simultaneous detection platforms have great potential, which will improve the efficiency of point of care detection. (3) The researchers also need to focus on some important problems. For examples, the upconversion luminescence efficiency of UCNPs is difficult to maintain, the synthesis method is complex, and the surface modification degree and functionalization are difficult to control.

Objective To explore the effect of Wenyang Huazhuo Tongluo recipe on pulmonary microvascular injury in mice with scleroderma based on mitophagy.Methods Fifty mice were randomly divided into blank control group(0.9％NaCl,by gavage),control group(0.9％NaCl,by gavage),model group,Wenyang Huazhuo Tongluo recipe group(47mg·kg-1·d-1 Wenyang Huazhuo Tongluo recipe by gavage),positive control group(10 mg·kg-1·d-1 KC7F2 dissolved in phosphate buffer solution intraperitoneal injection),continuous administration for 4 weeks.The expression levels of in vitro membrane translocation enzyme 20(TOMM20),hypoxia inducible factor-1α(HIF-1α),B cell lymphoma-2/adenovirus E1B-19 kDa interacting protein 3(BNIP3),PTEN inducible muscle enzyme protein 1(PINK1)and E3 ubiquitin ligase(Parkin)in lung tissue were detected by immunohistochemistry(IHC).Western blot(WB)was used to detect the expression levels of mitophagy-related proteins(TOMM20,LC3B)and HIF-1α/BNIP3/PINK1/Parkin pathway proteins in pulmonary microvascular endothelial cells.Results The relative content of HIF-1α in microvascular endothelial cells of lung tissue in the control group,model group,Wenyang Huazhuo Tongluo recipe group and positive control group were 0.17±0.02,0.98±0.01,0.66±0.03 and 0.48±0.01;the relative content of BNIP3 were 0.40±0.02,0.74±0.01,0.56±0.01 and 0.60±0.02;the relative content of PINK1 were 0.26±0.04,0.88±0.01,0.65±0.02 and 0.67±0.02;the relative contents of Parkin were 0.33±0.02,0.89±0.01,0.65±0.02 and 0.77±0.02;the relative contents of TOMM20 were 1.10±0.02,0.58±0.01,1.02±0.01 and 0.98±0.03;the relative contents of LC3B-Ⅰ/LC3B-Ⅱ were 0.24±0.01,0.80±0.01,0.53±0.02 and 0.70±0.02,respectively.The content of HIF-1α,BNIP3,PINK1,Parkin and LC3B-Ⅰ/LC3B-Ⅱ in model group was higher than those in control group.Wenyang Huazhuo Tongluo recipe can effectively reduce its content.The content of TOMM20 in the model group was lower than that in control group,and Wenyang Huazhuo Tongluo recipe can effectively increase its content.Conclusion Wenyang Huazhuo Tongluo recipe may inhibit mitophagy and improve SSc pulmonary microvascular injury by increasing TOMM20 and inhibiting the protein expression of LC3B and HIF-1α/BNIP3/PINK1/Parkin signaling pathway.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To explore the correlation between grip strength promotion and improvement of body composition and metabolic disorders in health examination population of different genders.Methods:In this retrospective cohort study, clinical data of 600 people who received health examination and grip strength check-up two times or more in the Medical Examination Center of Peking University Third Hospital from January 2018 to November 2022 were selected. The general data, physical examination, biochemical parameters, body composition and grip strength results were collected. After the first physical examination, the grip strength test was conducted, appropriate resistance strength exercises were given based on individual evaluation results. A health lecture was held, and the information related to health exercise was pushed through WeChat official account every week. The grip strength test was completed at the same time at the second physical examination, and the difference between the two test results was calculated before and after the second physical examination. The generalized estimation equation was used to analyze the correlation between the improvement of grip strength and the improvement of body composition and metabolic disorders in different gender health-check population.Results:In man and women, the body mass index [(25.50±3.66) vs (25.33±3.74) kg/m 2, (22.41±3.55) vs (22.25±3.46) kg/m 2] and grip strength [(42.71±7.30) vs (41.77±7.36) kg, (25.28±5.30) vs (23.98±4.87) kg] at the second health check-up were all significantly higher than those at the first time, and the diastolic blood pressure [(72.79±10.30) vs (74.47±9.85) mmHg (1 mmHg=0.133 kPa), (66.93±8.90) vs (68.92±9.42) mmHg] and serum homocysteine [(17.96±14.09) vs (19.27±14.26) μmol/L, (9.47±3.91) vs (10.26±3.90) μmol/L] were all significantly lower than those at the first time (all P<0.05). Among man, the low-density lipoprotein cholesterol (LDL-C) at the second physical examination was significantly lower than that at the first time [(2.94±0.78) vs (3.00±0.69) mmol/L] (all P<0.05). Among women, the systolic blood pressure and uric acid at the second health check-up were both significantly lower than those at the first time [(109.34±12.85) vs (110.54±12.32) mmHg, (276.91±62.46) vs (287.16±68.78) μmol/L], and the waist-hip ratio was significant higher (85.8%±5.1% vs 85.4%±5.0%) (all P<0.05). In males, the decreased aspartate aminotransferase ( OR=0.932, 95% CI: 0.888-0.978) and the increased skeletal muscle index ( OR=75.370, 95% CI: 29.012-195.806) were both positively correlated with the elevation of grip strength (all P<0.05); and in females, the decreased homocysteine ( OR=0.876, 95% CI: 0.782-0.982) and glycosylated hemoglobin ( OR=0.423, 95% CI: 0.222-0.805) and increased skeletal muscle index ( OR=22.918, 95% CI: 11.114-47.256) were all positively correlated with the elevation of grip strength (all P<0.05). Conclusion:There is a positive correlation between the improvement of grip strength and the improvement trend of body composition and metabolic disorders in in health examination population of different genders.

Objective:To explore the clinical outcome and applicability of the comb flap technique and stepwise design concept in plastic aesthetic and reconstructive surgery.Methods:The clinical data of patients who underwent plastic aesthetic and reconstructive surgery with the comb flap technique in Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2022 were retrospectively analyzed. The application of the comb flap technique follows the concept of stepwise design, that was, preoperative and intraoperative design and adjustment were carried out step by step and in sequence, and the design was combined with the surgical procedure. Its main operations included: an incision was designed along the edge of the target area, the tissue flap was widely separated at the base of the target area. The tissue flap was cut in sequence perpendicular to the cutting edge and temporarily sutured and fixed, the edge was cut and fixed. During the operation, the tension of the incision and the local appearance could be adjusted. The incisal edge was finely sutured, and the temporary suture was finally removed. The healing of surgical incision and complications were observed after the operation, and the facial recovery and surgical effect were followed up.Results:Six patients were enrolled, including 3 males and 3 females, aged from 2 to 58 years. One patient underwent upper eyelid tightening and lower eyelid blepharoplasty through subeyebrow incision. One patient underwent middle and lower face rhytidectomy. One patient underwent thick lip thinning and right facial liposuction. One patient underwent facial congenital melanocytic nevi resection. One patient underwent eyebrow congenital melanocytic nevus resection. One patient underwent facial flap repair. All patients had primary healing of incision, and no surgery-related complications occurred. All patients were followed up for 3 to 18 months, and all patients were satisfied with the surgical effect.Conclusion:The application of comb flap technique and stepwise design concept in plastic aesthetic and reconstructive surgery can delicately adjust the alignment of the incision margin, make the tension evenly distributed, and reduce the risk of scar formation and deformity after the operation. It has a wide range of clinical applications and good applicability.

Objective To investigate the effect of Yigong San(YGS)on learning and memory abilities of rats with lipopolysaccharide(LPS)-induced cognitive decline and explore its possible mechanism in light of intestinal microbiota.Methods Forty SD rats were randomly divided into control group,model group,donepezil(1.3 mg/kg)group,and high-dose(5.25 g/kg)and low-dose(2.63 g/kg)YGS treatment groups.After 24 days of treatment with the corresponding drugs or water by gavage,the rats in the latter 4 groups received an intraperitoneal injection of LPS(0.5 mg/kg)to establish models of Alzheimer's disease(AD).Water maze test and HE staining were used to evaluate the changes in learning and memory abilities and pathomorphology of the hippocampus.The changes in gut microbial species of the rats were analyzed with 16S rRNA sequencing,and the levels of IL-6,TNF-α,and IL-1β in the brain tissue and serum were detected using ELISA.Results Compared with the AD model group,the YGS-treated rats showed significantly shortened escape latency on day 5 after modeling,reduced neuronal degeneration and necrosis in the hippocampus,lowered pathological score of cell damage,and decreased levels IL-6,TNF-α and IL-1β in the brain tissue and serum.The YGS-treated rats showed also obvious reduction of Alpha diversity indicators(ACE and Chao1)of intestinal microbiota with significantly increased abundance of Prevotellaceae species at the family level and decreased abundance of Desulfovibrionaceae,which were involved in such metabolic signaling pathways as cell community prokaryotes,membrane transport,and energy metabolism.Conclusion YGS improves learning and memory abilities and hippocampal pathomorphology in AD rat models possibly by regulating the abundance of intestinal microbial species such as Prevotellaceae to affect the metabolic pathways for signal transduction,cofactors,and vitamin metabolism.

Objective To explore the mechanism by which Yigong San(YGS)improves learning and memory abilities of APP/PS1 transgenic mice in light of cerebral fluid metabolism regulation.Methods Three-month-old male APP/PS1 transgenic mice and wild-type C57BL/6 mice were both randomized into control group,model group,donepezil(1.67 mg/kg)group,and YGS(7.5 g/kg)group and received the corresponding treatments via gavage once daily for one month.After the treatments,the mice were assessed for learning and memory functions using Morris water maze test and examined for hippocampal and cortical pathologies and amyloid plaques using HE,immunohistochemical and thioflavin S staining;ELISA and Evans blue method were used for detecting Aβ1-40 and Aβ1-42 levels in the brain tissue and serum and assessing blood-brain barrier(BBB)integrity.Immunofluorescence colocalization was used to investigate AQP4 polarization on astrocytes.Western blotting was performed to detect the expressions of VE-cadherin,ZO-1,occludin,β-amyloid precursor protein(APP),BACE1,insulin-degrading enzyme(IDE),LRP1,RAGE,and AQP4 proteins.Results Compared with the control mice,APP/PS1 mice showed significant impairment of learning and memory abilities,increased degeneration or necrosis of hippocampal and cortical neurons,pathological scores,Aβ-positive plaques,elevated Aβ1-40 and Aβ1-42 levels in the brain tissue and serum,increased BBB permeability,upregulated RAGE expression,lowered expressions of VE-cadherin,LRP1,ZO-1,occludin,and AQP4 proteins,and reduced AQP4-expressing GFAP-positive cells.YGS treatment significantly improved the performance of the transgenic mice in Morris water maze test,reduced hippocampal and cortical pathologies and Aβ-positive plaques,and ameliorated the abnormal changes in Aβ1-40 and Aβ1-42 levels,BBB permeability,protein expressions of RAGE,VE-cadherin,LRP1,ZO-1,occludin and AQP4,and the number of AQP4-expressing GFAP-positive cells.Conclusion YGS improves learning and memory changes in APP/PS1 mice by ameliorating neuronal damage and Aβ pathology in the brain and regulating brain fluid metabolism.

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.

AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.