This paper summarizes Professor Gao Jiansheng's clinical experience in treating herpes simplex keratitis （HSK） based on the theory of hidden pathogens. It is believed that the core pathogenesis of HSK involves deficiency of vital qi and the internal presence of pathogenic factors. In the early stage， the pathogenesis is characterized by lung and spleen qi deficiency and invasion of external pathogens. In the middle stage， pathogenesis worsens due to latent pathogens damaging the vital qi and spleen deficiency with dampness. In the late stage， kidney yang deficiency and lingering pathogenic toxins are the root cause of recurrent attacks. In clinical practice， it is recommended to strengthen and protect the vital qi. In the early stage， the Modified Yupingfeng Powder （玉屏风散） is used. In the middle stage， the Modified Linggui Zhugan Decoction （苓桂术甘汤） is used. In the late stage， a self-formulated Modified Bushen Tuodu Fomulation （补肾托毒方） is applied. Additionally， herbs of tonifying qi and strengthening the exterior are used throughout the treatment to reduce recurrence.

Background China is the world's largest producer and consumer of cobalt. Skin exposure to excess cobalt can cause symptoms such as contact dermatitis. At present, there are few studies on skin contact of cobalt and its compounds. Objective To investigate the skin contact characteristics of cobalt and its compounds. Methods A cross-sectional study was conducted in February 2024 involving 70 workers from a hard metal tool manufacturing company and the workers were divided into four groups according to their job positions: powder mixing, sintering, automatic pressing, and grinding processing. General demographic information was collected through questionnaires. Workplace air samples were collected using personal samplers, and cobalt concentrations in workplace air were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Skin samples were collected from the workers' foreheads using cotton swabs, and urine samples were collected within 30 min after the end of their shift. Urine specific gravity was measured immediately after collection, and disqualified samples were discarded. Cobalt concentrations in the swab extracts and urine were determined by inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis was performed using Kruskal-Wallis test for multiple group comparisons, Mann-WhitneyU test for pairwise comparisons, Chi-square test for categorical variables, and Spearman's rank correlation analysis to examine the correlations among air, dermal, and urinary cobalt levels. Results The 8 h time-weighted average (TWA) cobalt concentration was (2.30±2.15) μg·m⁻³ (\begin{document}$ \bar{x}\pm s $\end{document}). The median skin exposure level was 53.8 ng·cm⁻², with a range of 4.25 ng·cm⁻² to 1090.2 ng·cm⁻². The median urinary cobalt level was 3.74 µg·L⁻¹, with a range of 0.83 to 382.9 µg·L⁻¹. Statistically significant differences in TWA cobalt concentration, skin exposure levels, and urinary cobalt levels were found between different work positions (H=9.012, P=0.029; H=16.348, P＜0.001; H=11.078, P=0.011). A positive correlation was observed between skin exposure levels and urinary cobalt levels (r=0.537, P＜0.01). Conclusion Skin contact may be one of the main sources of cobalt levels in urine. Therefore, it is essential for workers to improve skin protection and hygiene practices.

Benign essential blepharospasm(BEB)is a neurological disorder characterized by involuntary contractions of periocular muscles, which can lead to functional blindness and significantly impair patients' quality of life. This article systematically reviews the epidemiology, clinical manifestations, pathogenesis, and therapeutic advances in BEB. Epidemiological data indicate that the global prevalence of BEB is approximately 1 in 200000, with a predilection for individuals over 50 years of age and a significantly higher incidence in female than in male. The exact pathogenesis of BEB remains incompletely understood, though current evidence suggests close associations with neurotransmitter dysfunction, reduced cortical inhibition, and genetic susceptibility. Therapeutic strategies primarily focus on symptomatic management. Botulinum toxin type A(BTX-A)injection remains the first-line treatment but requires repeated administrations due to transient efficacy. Other treatments, including oral drugs, surgery, and repetitive transcranial magnetic stimulation, also have major limitations. By synthesizing recent research progress from domestic and international studies, this review aims to provide novel insights for the clinical management of BEB, ultimately improving patient outcomes.

Objective:To analyze the incidence of liver function injury in patients infected with 2019-nCoV omicron variant and its influencing factors.Methods:The clinical data and laboratory findings of 897 COVID-19 patients infected with omicron variant in Zhejiang province from February 23 to July 14, 2022 were retrospectively analyzed. Patients were divide into liver function injury group ( n=243) and non-liver function injury group ( n=654) based on liver function indicators. The clinical characteristics and laboratory tests were compared between the two groups, and influencing factors of liver function injury were analyzed. SPSS 26.0 statistical software was used for data analysis. Results:The incidence of liver injury in this series was 27.09% (243/897). The median age of patients in liver injury group was older, the body mass index (BMI) was higher( Z=-6.237 and -2.166, both P<0.05), the proportions of patients with hypertension and diabetes, and with severe clinical classification were higher ( χ2=17.087, 27.509 and 12.945, all P<0.01) ; the proportion of vaccinated patients was lower ( χ2=17.766, P<0.01) than those in non-liver injury group. The levels of platelet, hemoglobin, albumin and potassium in liver injury group were lower than those in non-liver injury group ( Z=-4.631, -2.368, -10.593 and -2.141, all P<0.05), while serum ALT, AST, γ-GT, urea nitrogen, glucose and hs-CRP levels were higher than those in the non-liver injury group ( Z=-7.451, -8.663, -4.410, -3.824, -3.278 and -3.884, all P<0.01). Multivariate Logistic regression analysis showed that age ( OR=2.580, 95% CI 1.429-4.657, P=0.002), history of diabetes ( OR=3.650, 95% CI 1.698-7.849, P=0.001), and decreased hemoglobin ( OR=1.993, 95% CI 1.066-3.726, P=0.031) and increased hs-CRP ( OR=1.797, 95% CI 1.283-2.517, P=0.001) were risk factors associated with liver function injury, while vaccination ( OR=0.499, 95% CI 0.312-0.798, P=0.004) was the protective factor for liver function. Conclusion:Liver function injury is frequently observed in COVID-19 patients infected with omicron variant, which is linked to age, underlying disease, and elevated inflammatory markers; while vaccination can lower the risk of liver injury in infected patients.

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress

Objective:To analyze the characteristics of adverse events of active medical devices in Shandong province, as well as the impact of device use duration on the risk rate of adverse events, for reference in improving the monitoring system of active medical device adverse events in China and the level of hospital medical quality management.Methods:The data came from the adverse event reporting data of active medical devices collected by Shandong Adverse Drug Reaction Monitoring Center from January 2019 to October 2021. The R software was used to analyze the distribution, cause and severity of adverse events, and a linear regression model of adverse event risk rate(Y) and adverse event time point(X) was established.Results:A total of 35 254 adverse events of active devices were included, of which 3 059 were serious injuries. The province/municipality with the largest number of reported adverse events was Shanghai(8 006 cases), and the least was Hainan province(4 cases); The majority of adverse events were reported by hospitals, with 34 056(96.60%). The medical devices reporting a higher number of adverse events were ventilators(688 cases), monitors(4 623 cases), infusion pumps(1 079 cases), syringe infusion pumps(1 995 cases), medical electron accelerators(529 cases)and infant incubators(513 cases). In the linear regression model, the risk rate of adverse events increased with the useduration of the device when 0.00%≤ X<14.14%; the risk rate of adverse events decreased with the increase of service time when 14.14%≤ X<100.00%. Conclusions:The number of adverse events reported in each province is different, and hospitals are the main reporting units.The causes of adverse events of different medical devices indicate different correlation strengths with the product itself. The use duration of medical devices poses a great impact on the risk rate of adverse events.

【Objective】 To analyze the clinical and pathological characteristics of mucinous tubular and spindle cell carcinoma （MTSCC） in the kidney so as to evaluate the value of radiotherapy in local treatment of refractory MTSCC. 【Methods】 A case of MTSCC with recurrent recurrence and metastasis was reported， and the existing literature on MTSCC was reviewed and analyzed to explore the value of radiotherapy in the treatment of MTSCC. 【Results】 After three operations， postoperative pathology of the patient showed mucinous tubular and spindle cell carcinoma of the kidney. Radiotherapy was performed in the first recurrence area， and long-term follow-up in the tumor bed area showed no recurrence. 【Conclusion】 MTSCC， a rare renal epithelial tumor， has the low-grade malignance in most cases， and rarely recurs and has metastasis. This patient had repeated recurrence and metastasis before surgery， but after tumor bed radiotherapy after the first recurrence no lesion was found， suggesting that radiotherapy plays a certain role in preventing local recurrence. It is necessary to further explore the value of radiotherapy in the treatment of MTSCC.

Background: A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. Conclusion Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.

【Objective】 To clone the full-length of human kidney and brain protein (KIBRA) coding sequence in eukaryotic expression vector and provide a model for studying the biological function of KIBRA in breast cancer cells. 【Methods】 Total RNA of human breast cancer cell line MCF7 was extracted. After reverse transcription, the full length of KIBRA (NM_001161661.2) coding region was amplified by PCR, and cloned into eukaryotic expression vector pCMV-Blank. After identification, it was defined officially as pCMV-KIBRA. Then it was transfected into MCF7 cells, and the expression of KIBRA was detected by real-time PCR and Western blotting after 48 hours. The primary, secondary and tertiary structures and post-transcriptional modification sites of KIBRA were analyzed with bioinformatics software. 【Results】 Bacterial PCR, double enzyme digestion and DNA sequencing results showed that the correct sequence of KIBRA was inserted into the vector pCMV-KIBRA. The mRNA and protein expressions of KIBRA were significantly increased in MCF7 cells transfected with pCMV-KIBRA. Bioinformatics analysis showed that KIBRA was composed of 1119 amino acids. There were 52 phosphorylation sites, 1 acetylation site and 5 ubiquitination sites, and the protein structure was mainly α-helix and random coil. 【Conclusion】 The eukaryotic expression vector of full-length of human KIBRA coding sequence was successfully constructed and overexpressed in breast cancer cell line MCF7, which can lay a foundation for studying the biological function of KIBRA in breast cancer.

ObjectiveTo investigate the association of the expression of the NK cell-activating receptor NKG2D, its ligand major histocompatibility complex class I chain-related gene A (MICA), and related cytokines ［interferon-γ (IFN-γ), interleukin-10 (IL-10), and interleukin-15 (IL-15)］ with intrahepatic inflammation in primary biliary cholangitis (PBC). MethodsLiver biopsy specimens were collected from 30 patients with PBC (PBC group), 15 patients with chronic hepatitis B (CHB group), and 10 patients with nonalcoholic fatty liver disease (NAFLD group), who were hospitalized in The Second Affiliated Hospital of Kunming Medical University from August 2014 to June 2015. The degree of liver inflammation (G) and fibrosis degree (S) of the liver specimens were determined, and immunohistochemistry was used to measure the expression of NKG2D, MICA, IFN-γ, IL-10, and IL-15 in liver tissue (the scores were determined based on the number of cells stained and the degree of staining to evaluate the expression of each marker). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the t-test was used for comparison between two groups; a Spearman correlation analysis was used to investigate correlation. ResultsIn the PBC group, the expression of NKG2D increased with the degree of inflammation, and the patients with G3-4 inflammation had significantly higher expression than those with G1-2 inflammation (G1 vs G2 vs G3 vs G4: 1.4±0.05 vs 1.56±0.05 vs 1.86±0.11 vs 2.60±0.17, F=150.8, P＜0.05); the expression of NKG2D decreased with fibrosis degree (S3 vs S4: 2.30±0.17 vs 1.56±0.05, t=-1.52, P＜0.05). In the PBC group, there was no significant difference in MICA between G3 and G4 (0.11±0.01 vs 0.20±0.03, t=-2.20, P＞0.05) and between S3 and S4 (0.12±0.02 vs 0.18±0.03, t=-2.64, P＞0.05). In the PBC group, there was a significant difference in the expression of IL-15 between the patients with different degrees of inflammation (G1 vs G2 vs G3 vs G4: 0.70±0.10 vs 1.50±0.10 vs 1.93±0.11 vs 2.60±0.17, F=251.3, P＜0.05), while there was no significant difference between the patients with different fibrosis degrees (S3 vs S4: 2.00±0.05 vs 2.40±0.30, t=-1.62, P＞0.05). In the CHB group, there was a significant difference in the expression of IL-15 between the patients with different degrees of inflammation (G1 vs G2 vs G3: 0.73±0.15 vs 1.96±0.15 vs 2.50±0.17, F=150, P＜0.05) and between the patients with different fibrosis degrees (S1 vs S2 vs S3: 0.70±0.10 vs 21.96±0.15 vs 2.50±0.17, F=158.7, P＜0.05). In the PBC group, the expression of IL-10 was only observed in the patients with G1 inflammation (0.16±0.01), and in the CHB group, the expression of IL-10 was observed in the patients with G1 and G2 inflammation, with no significant difference (G1 vs G2: 0.19±0.01 vs 0.13±0.01, t=-1.522, P＞0.05). In the patients with PBC, the expression of IL-15 in liver tissue was positively correlated with the levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) (r=0.241 and 0.407, P=0.014 and 0.045). ConclusionThe NK cell-activating receptor NKG2D affects the degree of intrahepatic inflammation in PBC, and the NKG2D ligand MICA is expressed in the advanced stage of PBC and can downregulate NKG2D. The expression of IL-15 increases with the degree of inflammation in PBC and is positively correlated with the levels of ALP and GGT, suggesting that the activation of NK cells and abnormal secretion of cytokines are involved in the development and progression of PBC and IL-15 may be used as an auxiliary index for the diagnosis of PBC.