Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

OBJECTIVE To analyze the clinical characteristics of Stevens-Johnson syndrome （SJS） and toxic epidermal necrolysis （TEN） induced by tislelizumab， providing evidence for clinical medication safety. METHODS Case reports of tislelizumab-related SJS/TEN were retrieved from CNKI， VIP， Wanfang Data， PubMed， ScienceDirect， and Embase. Descriptive analysis was performed. RESULTS Seventeen cases from 17 publications were included （SJS 4 cases， TEN 13 cases）. Among them， there were 10 males and 7 females. Twelve patients were aged between 70 and 79 years. The predominant tumor type was lung cancer （10 cases）. Thirteen patients received combination therapy with chemotherapeutic drugs. The median onset time of SJS/ TEN was 26 （4， 104） days. Nine patients developed SJS/TEN after the first administration of the drug. Sixteen patients exhibited prodromal rash symptoms， primarily characterized by severe skin damage such as skin detachment， accompanied by mucosal injury. Sixteen patients improved after symptomatic treatment， while one patient died. CONCLUSIONS Tislelizumab-associated SJS/TEN risk is higher in elderly patients， males， those with lung cancer and those receiving combination chemotherapy. Mucosal lesions and atypical rashes may indicate the early onset of SJS/TEN. During clinical use， pharmaceutical care can be carried out through measures such as identifying high-risk populations， closely monitoring skin symptoms from the first administration to the fifth treatment cycle， and enhancing patient education. When relevant symptoms occur， the medication should be promptly discontinued and symptomatic treatment should be administered to ensure the patient’s medication safety.

Objective:To investigate the value of 24 h urinary aldosterone(24 h-UAC) measurement by liquid chromatography-tandem mass spectrometry(LC-MS/MS) in the subtype classification of primary aldosteronism(PA).Methods:A total of 86 patients with PA, including 51 with unilateral primary aldosteronism(UPA) and 35 with bilateral primary aldosteronism(BPA), were enrolled in the Department of Endocrinology and Metabolism at West China Hospital between January 2018 and December 2022. Plasma aldosterone concentration(PAC), plasma renin concentration(PRC) and 24 h-UAC were measured by LC-MS/MS. 24-hour urinary electrolytes and 24-hour urinary creatinine(24 h-UCR) were also measured. The diagnostic value of 24 h-UAC in PA subtype classification was evaluated using receiver operating characteristic(ROC) curve analysis. Multivariate logistic regression analysis was conducted with PA subtypes as the dependent variable(UPA=1, BPA=0) to establish a diagnostic model for differentiating unilateral from bilateral lesions, and its performance was compared with published Chinese classification models. Results:There were no statistical differences between the UPA and BPA groups in terms of age, gender, BMI, systolic and diastolic blood pressure, 24 h urinary potassium, sodium, chloride, 24 h-UCR and PRC( P<0.05). The lowest plasma potassium level was significantly lower in the UPA group than in the BPA group, while PAC, 24 h-UAC, aldosterone-renin ratio(ARR), and 24 h-UAC/UCR were significantly higher( P<0.05). The detection rate of typical adenomas on imaging also showed a significant difference between the two groups( P<0.05). The area under the ROC curve(AUC) of 24 h-UAC for differentiating UPA from BPA was 0.829(95% CI 0.733-0.902), with an optimal cut-off value of 15.4 μg/24 h, yielding a sensitivity of 68.63% and a specificity of 88.57%( P<0.001). At a cut-off value of 24.5 μg/24 h, specificity reached 100%, with a sensitivity of 27.45%. Multivariate analysis indicated that a combined model incorporating 24 h-UAC, the lowest plasma potassium level, and imaging findings of typical adenomas significantly improved diagnostic accuracy for PA subtyping, achieving a specificity of 91.43%. Compared with the existing Chinese modified Küpers scoring model and CONPASS prediction model, this model demonstrated higher diagnostic efficiency, a lower missed diagnosis rate, and a misdiagnosis rate intermediate between the two. Conclusion:The 24 h-UAC in UPA patients is significantly higher than in BPA patients, making it a valuable marker for PA subtype classification. A predictive model combining 24 h-UAC, the lowest plasma potassium level, and imaging evidence of typical adenomas demonstrated high diagnostic accuracy for PA subtype classification and may provide valuable guidance for clinical decision-making.

Objective:To investigate the value of 24 h urinary aldosterone(24 h-UAC) measurement by liquid chromatography-tandem mass spectrometry(LC-MS/MS) in the subtype classification of primary aldosteronism(PA).Methods:A total of 86 patients with PA, including 51 with unilateral primary aldosteronism(UPA) and 35 with bilateral primary aldosteronism(BPA), were enrolled in the Department of Endocrinology and Metabolism at West China Hospital between January 2018 and December 2022. Plasma aldosterone concentration(PAC), plasma renin concentration(PRC) and 24 h-UAC were measured by LC-MS/MS. 24-hour urinary electrolytes and 24-hour urinary creatinine(24 h-UCR) were also measured. The diagnostic value of 24 h-UAC in PA subtype classification was evaluated using receiver operating characteristic(ROC) curve analysis. Multivariate logistic regression analysis was conducted with PA subtypes as the dependent variable(UPA=1, BPA=0) to establish a diagnostic model for differentiating unilateral from bilateral lesions, and its performance was compared with published Chinese classification models. Results:There were no statistical differences between the UPA and BPA groups in terms of age, gender, BMI, systolic and diastolic blood pressure, 24 h urinary potassium, sodium, chloride, 24 h-UCR and PRC( P<0.05). The lowest plasma potassium level was significantly lower in the UPA group than in the BPA group, while PAC, 24 h-UAC, aldosterone-renin ratio(ARR), and 24 h-UAC/UCR were significantly higher( P<0.05). The detection rate of typical adenomas on imaging also showed a significant difference between the two groups( P<0.05). The area under the ROC curve(AUC) of 24 h-UAC for differentiating UPA from BPA was 0.829(95% CI 0.733-0.902), with an optimal cut-off value of 15.4 μg/24 h, yielding a sensitivity of 68.63% and a specificity of 88.57%( P<0.001). At a cut-off value of 24.5 μg/24 h, specificity reached 100%, with a sensitivity of 27.45%. Multivariate analysis indicated that a combined model incorporating 24 h-UAC, the lowest plasma potassium level, and imaging findings of typical adenomas significantly improved diagnostic accuracy for PA subtyping, achieving a specificity of 91.43%. Compared with the existing Chinese modified Küpers scoring model and CONPASS prediction model, this model demonstrated higher diagnostic efficiency, a lower missed diagnosis rate, and a misdiagnosis rate intermediate between the two. Conclusion:The 24 h-UAC in UPA patients is significantly higher than in BPA patients, making it a valuable marker for PA subtype classification. A predictive model combining 24 h-UAC, the lowest plasma potassium level, and imaging evidence of typical adenomas demonstrated high diagnostic accuracy for PA subtype classification and may provide valuable guidance for clinical decision-making.

Objective To investigate the current status of application of the Confusion assessment method for the Intensive Care Unit (Cam-ICU),and to explore its influencing factors.Methods A total of 300 patients admitted to were enrolled.The researchers and nurses used Cam-ICU to assess patients' delirium,respectively,and the differences in deliriun assessment were analyzed.Results For delirium assessment,the Kappa value was 0.546 between the researchers and nurses.The consensus rate was 17.6％ for hypoactive delirium,and 77.8％ for hyperactive delirium in 44 delirium patients.Logistic regression analysis showed that APACHE Ⅱ score,RASS score and delirium type were influencing factors of accurate assessment of delirium.Conclusion The consistence of assessment of delirium by ICU nurses is generally good,but the accuracy of assessment of hypoactive delirium is the worst.

Objective To explore the relationship between blood lipid level and primary open angle glaucoma(POAG)and intraocular pressure(IOP).Methods A retrospective case-control study was designed.80 POAG patients from EYE & ENT hospital of FUDAN university were collected as a case group from January 2015 to May 2016.Meanwhile 80 age and gender matched healthy people were collected as a control group.The differences of gender in men subgroup (POAG:44,Control:39) and female subgroup (POAG:36,Control:41) showed no statistic significance.Serum total cholesterol(TC),total triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein A(Apo A) and apolipoprotein B(Apo B) were measured using Roche automatic biochemical analyzer.The analysis of the above mentioned lipid levels between POAG group and control group was conducted by independent student′s T test and multivariate logistic regression.The relationship between lipid level and IOP was analysied using Pearson correlation test.Results The TG level was (1.40±0.71)mmol/L in the POAG group,(1.00±0.37)mmol/L in the control group.The difference had statistic significance (t=4.467,P<0.001).The HDL-C level in the POAG group was (1.22±0.36)mmol/L,(1.38±0.25)mmol/L in the control group.The difference also had statistic significance (t=-3.228,P=0.002).Comparison between the men subgroup and female subgroup found that the TG level in the POAG group of men was (1.47±0.71)mmol/L,(1.01±0.36) mmol/L in the control group and the HDL-C level were (1.14±0.31) mmol/L,(1.32±0.20)mmol/L in two groups.Both the level of TG and HDL-C had statistic significance in men (t=3.717,P<0.001;t=-3.240,P=0.002).The TC,TG level in the POAG group and control group of women respectively were (4.59±0.81)mmol/L,(1.33±0.72)mmol/L and (4.21±0.64)mmol/L,(0.99±0.38)mmol/L.Both blood level were significantly higher than the control group in women (t=2.278,P=0.026;t=2.503,P=0.016).Logistic regression analysis showed that the TG level correlated with POAG (P=0.004,OR=2.831,95% CI=1.392-5.759)and both POAG in the men and women (P=0.025,OR=3.223,95% CI=1.156-8.989;P=0.045,OR=2.554,95% CI=1.020-6.395).Pearson test showed that the TG level of POAG patients was positively associated with IOP in spite of gender(P<0.05).Conclusion The peripheral blood level of TG was significantly increased in the POAG patients and significantly correlated with IOP,which indicated that the increased peripheral blood level of TG may be the independent risk factor for the POAG..

Objective In order to explore the association between complement C3 and primary open angle glaucoma (POAG),the serum complement C3 level was detected and the polymorphism of the C3 exon gene was analyzed in patients with POAG.Methods A prospective case-control study was designed.A total of 45 patients with POAG visiting Eye &ENT hospital of Fudan University were collected from December 2014 to December 2015,and 45 age-/gender-matched healthy subjects from yearly health screening were collected as normal controls.Serum C3 concentration was detected by immunoturbidimetric assay.Meanwhile,genomic DNA was extracted from peripheral blood leukocytes,and sequencing for C3 exons was followed with PCR to analyze the gene polymorphism.Statistical analysis was performed by use of SPSS 20.0 software.Student's t test was used to evaluate the difference of serum C3 level between two groups.Chisquare test was used to analyze the difference in the distribution of C3 exon gene polymorphism between two groups.The one-way ANOVA was utilized to analyze the difference of serum C3 level among different genotypes of C3 exon.Results The serum level of C3 in POAG (104.81 ± 29.15)mg/dl was significantly lower (t =-3.162,P =0.002) compared to controls (121.06 ± 18.39) mg/dl.There were a total of seven single nucleotide polymorphisms (SNPs) (rs2230201,rs2230204,rs2230205,rs428453,rs423490rs7951,rs539822147) within the C3 exon gene region,but no mutation was detected.There was no difference in the frequency and distribution of these SNPs between POAG and controls,as well as,there was also no significant difference in serum C3 level among these SNPs genotypes.Conclusions Decreased serum C3 level in POAG patients indicated that complement C3 might be involved in the pathomechanism of glaucoma.No significant abnormality of C3 exon gene was detected,so the gene polymorphism having an impact on serum C3 level could be excluded as a reason probably.

Objective A large sample of multi-factor Logistic analysis of clinical biochemical indicators from elderly cataract patients were done to find the characteristics of possible changes in potential factors for cataract-related indicators and explore the pathogenesis of cataract from the perspective of laboratory diagnosis.Methods A retrospective case control study was conducted .Cataract patients from Eye-Ear Nose Throat Hospital of Fudan University were collected during June 2011 to July 2015 and routinely tested for 14 clinical biochemistry indicators including ALB , GLU, TP, GLB, BUN, URCA, Cr, LDH, ALP, Ca, Na, K, Cl, and P.The mean age of the 3 527 cataract patients (1 804 males, 1 723 females) was (64.47 ±11.29) years.Those data were reserved by LIS (Laboratory Information System) system and were retrieved for large data analysis . The control group was filtered from hospitalized patients besides cataract patients during January 2014 to July 2015.The mean age of the 3 333 control subjects ( 1 770 males, 1 563 females ) was ( 64.04 ±9.03 ) years.Biochemical indicators between cataract group and control group were analyzed by independent student′s t-test and Logistic regression .Meanwhile , the objects were divided into 3 groups according to the age (40-59 years,60-79 years,≥80 years) for independent student′s t-test with the control group respectively .Results There are no statistical difference in age ( t=1.663,P=0.096) and gender ( t=2.63,P=0.105 0) between cataract group and control group ( P>0.05).The results of Logistic regression between cataract group and control group were as follow : ALB (OR=1.053,95%CI=1.019-1.088),BUN(OR=1.113,95% CI=1.076-1.152),Cr(OR=1.007, 95%CI=1.003-1.010),GLB(OR=1.049,95% CI=1.018 -1.081),GLU(OR=1.175,95% CI=1.139-1.211),Cl(OR=1.059,1.032 -1.088),Na(OR=1.180,95% CI =1.150 -1.212).Those might be enrolled as risk factors for cataract (P<0.05).The level of ALB, GLU, Na and Cl in cataract group according to different age groups were significantly higher ( t=8.780,t=4.670, t=9.695, t=6.415, P<0.05) than that of control in 40-59 age group;the level of ALB, BUN, Cr, GLU, Na and Cl in cataract group was significantly higher ( t=4.974, t=9.414, t=4.123, t=6.906, t=14.741, t=9.212, P<0.05) than control in 60 -79 age group; the level of BUN, Cr, GLU, Na and Cl in cataract group was significantly higher (t=6.077, t=4.906, t=2.626, t=5.459, t=3.424, P<0.05) than control in 80-age group.Conclusions The level of ALB, BUN, GLB, Cr, GLU, Na and Cl in peripheral blood of cataract patients was significantly increased which suggested that those change might associated with the pathogenesis of cataract .

Purpose To compare and investigate the oncogenic and metastatic phenotypes in nude mice by injection of rat hepatocellu-lar carcinoma ( HCC) cells L2 via two different routes. Methods Twenty of 7-week-old female BALB/cA mice were randomly divided into 2 groups. After the injections of L2 from liver or spleen lobe, the survival rate, tumor formation rate, carcinogenic features, and metastasis were comparatively studied. Results All of the liver orthotopic nude mice developed liver cancer (100%) with 60% lung metastasis rate, and exhibited an expansive growing pattern with surrounding invasion. In the spleen orthotopic model, 78% mice de-veloped HCC in spleen, with 67% liver metastatic rate and 11% lung metastatic rate, lower than the liver orthotopic model ( P <0. 05). But the microscopically hilar lymph node metastasis rate was 33%. Conclusion The direct liver injection of L2 in female nude mice is a better modeling method for studying the mechanism of both carcinogenesis and metastasis, as well as the evaluation of therapeutic effect of liver cancer.