Oxidative stress is a pivotal factor in the onset and progression of diabetic kidney disease （DKD）， and it plays an essential role in the prevention and treatment of DKD. The "Gaozhuo" pathogenesis posits that DKD is characterized by the invasion of Gaozhuo and damage to the kidney collaterals， with the underlying cause being the insufficiency of spleen Qi and the internal formation of Gaozhuo， which provides valuable guidance on oxidative stress. The insufficiency of spleen Qi and the internal formation of Gaozhuo represent a dynamic， evolving process. Gaozhuo invades the kidney collaterals， impairs kidney Qi， and progressively leads to the congealing and stagnation of Gaozhuo and blood， ultimately resulting in the failure of both the spleen and kidneys. The damage caused by Gaozhuo to the kidney collaterals and kidney Qi is analogous to the organ and functional damage of the kidneys induced by excessive reactive oxygen species and oxidative stress. Damage to the kidney collaterals means organic injuries to the glomeruli， renal tubules， and renal interstitium， and the depletion of kidney Qi refers to damage to glomerular filtration and renal tubular reabsorption. The congealing and stagnation of Gaozhuo and blood in the kidney collaterals is similar to oxidative stress-induced thickening of the glomerular basement membrane and fibrosis. The interaction between spleen and kidney Qi deficiency and the congealing and stagnation of Gaozhuo and blood creates a vicious cycle that exacerbates the condition， ultimately evolving into the failure of both the spleen and kidneys. The failure of the spleen and kidneys is analogous to renal failure， and its extreme manifestation is end-stage renal disease and uremia. The treatment of oxidative stress in DKD with traditional Chinese medicine （TCM） is based on the principles of strengthening the spleen and tonifying the kidneys， and dispelling turbidity and removing blood stasis. According to the syndrome type， it is recommended to use methods such as strengthening the spleen and tonifying Qi while dispelling dampness and removing turbidity， strengthening the spleen and tonifying the kidneys while dispelling dampness and removing turbidity， strengthening the spleen and tonifying the kidneys while dispelling turbidity and removing blood stasis， or consolidating the spleen and kidneys while clearing away turbidity and blood stasis.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

Objective: To evaluate the intervention effectiveness of co-occurrence and prevention for myopia and obesity among primary and secondary school students, so as to provide a scientific basis for the development of comprehensive intervention measures in myopia and obesity. Methods: From September 2022 to September 2023, a cluster random sampling method was used to select 6 primary schools and 6 junior high schools from Tongzhou District, Beijing. Participants were randomly assigned to an intervention group (914 before intervention and 754 after intervention) and a control group (868 before intervention and 652 after intervention), with an expected duration of one academic year. Based on the RE-AIM framework, integrate resources from families, schools, communities, and medical institutions to develop a school-based intervention technology packagefor the co-occurrence and prevention of myopia and obesity in children. The intervention group received intervention according to the comprehensive intervention technology package, while the control group did not receive any intervention measures. Relevant health indicators during the baseline period and after intervention were measured and collected, and groups were compared by Chi quest test, t-test and Wilcoxon rank sum test. Results: After intervention, the uncorrected visual acuity of primary and secondary school students in the intervention group (4.79±0.30) and the control group (4.77±0.33) both decreased compared to those before intervention (4.80±0.30, 4.90±0.32) ( t =-7.00,-5.24); the decrease in uncorrected visual acuity in the intervention group was smaller than that in the control group( t =5.33)( P <0.01). After intervention, body mass index, waist circumference, hip circumference, and body fat percentage of primary and secondary school students in the intervention group decreased compared to those before intervention. However, the changes in these indicators were not statistically significant ( t/Z =-0.03, - 0.36，- 0.30，- 0.01, P >0.05); the above indicators in the control group increased compared to those before intervention, but only hip circumference and body fat percentage showed statistically significant changes ( t/Z =2.17, 2.62, P <0.05). After intervention, both the intervention group and the control group showed increases in systolic and diastolic blood pressure compared to those before intervention(intervention group: t =2.16,5.29; control group: t =6.84,5.07); the intervention group had lower systolic and diastolic blood pressure than the control group( t = -5.27 , -2.08)( P <0.05). After intervention, the intervention and the control groups had statistically significant differences in cognitive accuracy(92.48%, 69.33%) in terms of "outdoor exercise can prevent myopia" and "having 5 servings of adult fist sized vegetables and fruits every day" ( χ 2=6.30, 7.86, P <0.05). There was a statistically significant difference in the proportion of primary and secondary school students in the intervention group (40.98%) and the control group (35.43%) for "who did not drink sugary drinks for every day in the past 7 days" ( χ 2=4.32, P <0.05). After intervention, the intervention group and the control group showed increases in "school outdoor activity duration on school days" and "outdoor activity duration on rest days" compared to those before intervention ( t/Z =-13.32,-9.71;- 2.59，-2.69）；the behavior rate of "visual acuity measurement frequency at least once every 3 months" in the intervention group (46.68%) and the control group (52.76%) increased compared to those before intervention (36.43%, 44.01%), and the increases in the intervention group were greater than that in the control group ( χ 2=17.52,11.08) ( P <0.05). Conclusions Comprehensive intervention measures have significant intervention effects on controlling the occurrence and development of comorbidity of myopia and obesity in children. It could actively promote collaboration and cooperation among families, schools, communities and medical institutions to reduce the occurrence of myopia and obesity among primary and secondary school students.

AIM: To investigate the effect of intense pulsed light(IPL)combined with Yuyin Runmu formula fumigation and meibomian gland massage on the treatment of patients with meibomian gland dysfunction(MGD)-related dry eye.METHODS: Prospectively selected 198 cases(396 eyes)of MGD-related dry eye patients admitted to our hospital from November 2021 to November 2023, and they were randomly divided into 99 cases(198 eyes)in control group treated with fumigation of Yuyin Runmu formula and meibomian gland massage, and 99 cases(198 eyes)in observation group treated with combined IPL on the basis of the control group. The efficacy of the two groups was compared, as well as the changes in the levels of ocular indexes [tear film break-up time(BUT), Schirmer I test(SⅠt)], visual quality [objective scattering index(OSI), Strehl ratio(SR), and modulation transfer function(MTF)], lipid layer thickness(LLT)of the tear film, and changes in tear fluid levels of inflammatory factors [tumour necrosis factor-α(TNF-α)and transforming growth factor-beta 1(TGF-β1)].RESULTS: All the patients completely received the treatment and follow-up. The levels of BUT, SⅠt, SR, MTF, and LLT increased and the levels of OSI, TNF-α, and TGF-β1 decreased in the two groups at 2 mo after treatment(all P<0.001), and the observation group was more favourable(all P<0.001).CONCLUSION: IPL combined with Yuyin Runmu formula fumigation and meibomian gland massage is effective in treating MGD-related dry eye, improving patients' ocular parameters, visual quality, and LLT, and decreasing the levels of inflammatory factors in the tear fluid.

OBJECTIVE To investigate the efficacy and safety of ivabradine in the treatment of end-stage renal disease patients with chronic heart failure （CHF） during maintenance hemodialysis （MHD）. METHODS End-stage renal disease patients with CHF during MHD who were treated in our hospital from May 2021 to September 2023 and met the inclusion criteria were selected as the study subjects. They were randomly divided into control group and observation group， with 60 cases in each group， using a random number table method. Both groups of patients received MHD three times a week for 4 hours each time and were anticoagulated with low-molecular weight heparin sodium. At the same time， they were treated with CHF conventional therapy； based on the above treatment， observation group was orally administered Ivabradine tablets 5 mg， twice a day （if the resting heart rate was above 60 beats/min after 2 weeks， the drug dose was increased to 7.5 mg， twice a day）. Both groups of patients were treated continuously for 6 months. The clinical efficacy of 2 groups was compared as well as vital signs， cardiac function， the levels of heart failure- related biomarkers and inflammatory factors before and after treatment， and the incidences of dialysis-related hypotension and adverse drug reactions. RESULTS The effective rate of the observation group （92.45%） was significantly higher than that of the control group （76.47%）， and the incidence of dialysis-related hypotension （20.75%） was significantly lower than that of the control group （41.18%） （P＜0.05）. The heart rate， the levels of left ventricular end-systolic diameter， left ventricular end-diastolic diameter， serum N-terminal pro-B-type natriuretic peptide， cancer antigen 125， tumor necrosis factor-α， interleukin-6， and hypersensitive C-reactive protein in observation group after treatment were significantly lower than those of control group （P＜0.05）； the left ventricular ejection fraction and cardiac output were significantly higher than those in the control group （P＜0.05）. There was no statistically significant difference in the diastolic blood pressure， systolic blood pressure， or the total incidence of adverse drug reactions between the two groups after treatment （P＞0.05）. CONCLUSIONS Ivabradine can significantly improve cardiac function， inhibit ventricular remodeling， down-regulate serum levels of serum N-terminal pro-B-type natriuretic peptide and cancer antigen 125， decrease body inflammation levels and the incidence of dialysis-related hypotension in end-stage renal disease patients with CHF during MHD， with significant clinical effects and good safety.

Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

Objective: To analyze the distribution characteristics of fluoride and trichloromethane in drinking water in rural schools in Guizhou Province and assess their health risks, so as to provide a scientific basis for ensuring the safety of drinking water in rural schools. Methods: During the dry season (March to May) and wet season (July to September) of 2020 to 2022, 788 rural primary and secondary schools in agricultural counties (districts) in Guizhou Province were selected for investigation by using a direct sampling method. A total of 1 566 drinking water samples were collected from these schools, and the mass concentrations of fluoride and trichloromethane in the water samples were detected. The Mann-Whitney U test was used for intergroup comparison, and a health risk assessment model was employed to evaluate the health risks of students oral intake of fluoride and trichloromethane. Results: From 2020 to 2022, the mass concentrations of fluoride and trichloromethane in the drinking water of rural schools in Guizhou Province all met the standards, and the ranges were no detection to 0.99 mg/L and (no detection to 0.06)×10 -3 mg/L, respectively. The mass concentrations of fluoride in dry and wet seasons were 0.05(0.05,0.10), 0.05(0.05,0.10) mg/L, the mass concentrations of trichloromethane were [0.02(0.02,1.00)]×10 -3 , [0.02(0.02,1.00)]×10 -3 mg/L, the mass concentrations of fluoride in factory water and terminal water were 0.05(0.05,0.05), 0.05(0.05,0.10) mg/L, and the differences were not statistically significant ( Z=-0.04, -0.88, - 0.98 , P >0.05). There was a statistically significant difference in the mass concentration of trichloromethane between factory water and peripheral water [0.02(0.02,0.02)×10 -3 , 0.02(0.02,1.05)×10 -3 mg/L]( Z=-2.16, P < 0.05 ). The non-carcinogenic risk assessment values for students oral exposure to fluoride and trichloromethane were in the range of 0.01(0.01,0.03)-0.03(0.03,0.06) and [0.26( 0.26 ,14.54)]×10 -4 -[0.52(0.52,48.62)]×10 -4 , respectively, all of which were at acceptable levels; the carcinogenic risk assessment values for oral exposure to trichloromethane were in the range of [0.08(0.08, 4.51 )]×10 -7 -[0.16(0.16,15.07)]×10 -7 , indicating a low risk. Conclusions The health risks of students expore to fluoride and trichloromethane in drinking water in rural schools of Guizhou Province are low. It is necessary to strengthen the standardized management of disinfection in some rural drinking water projects and the monitoring of fluoride in water sources to reduce the exposure risk to children.

ObjectiveTo investigate the prevalence of high-risk HPV infection among women in Kashgar area， analyze related risk factors， conduct follow-up and health education interventions for positive cases in the past three years， and assess intervention outcomes to improve HPV screening awareness and reduce cervical cancer incidence. MethodsThis study randomly selected 571 women from Kashgar who underwent HPV screening as part of a health check-up in the First People’s Hospital of Kashgar between January 2021 and June 2023. High-risk HPV-DNA was detected using the PCR-RDB method. Based on the test results， participants were divided into HPV-negative and HPV-positive groups， and the infection rates and associated risk factors were analyzed. Additionally， follow-up was conducted for women who tested positive for high-risk HPV during the screening to assess the effectiveness of health management interventions. ResultsFrom 2021 to 2023， the high-risk HPV positive rate among women in Kashgar showed a year-on-year decline， recorded at 19.15%， 16.43%， and 11.30%， respectively （P<0.001）， with a total of 3，921 cases （16.13%） testing positive for high-risk HPV during this period. Uyghur women had a significantly higher infection rate compared with those of Han nationality and other ethnic minorities （P<0.05）. Risk factors included age， age at first sexual activity， number of sexual partners， contraceptive methods， and a history of vaginal inflammation （P<0.05）. Health management interventions significantly improved participants’ awareness scores regarding cervical cancer prevention and the proportion of women voluntarily receiving HPV vaccination （P<0.05）. ConclusionsHigh-risk HPV infection among Uyghur women in Kashgar area is relatively high， with single infection of HPV-16 and HPV-52 and mixed infections of HPV-16 +HPV-52 and HPV-16 +HPV-58 being predominant. Risk factors include age at first sexual activity， number of sexual partners， contraceptive methods， and history of vaginal inflammation. Through triple-education interventions， the incidence of cervical cancer in Kashgar has been effectively reduced， and standards for primary-level diagnosis， treatment， and health supervision have been improved.

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.