Guishenwan （GSW）， originating from Jingyue Quanshu （Zhang Jingyue's Complete Works）， is a classic traditional Chinese medicine （TCM） formula with a history of over 400 years. Designed for kidney essence deficiency syndrome， it is clinically applied to treat diseases associated with essence-blood deficiency， such as ovarian insufficiency diseases in women， oligospermia-induced infertility in men， and lumbar disc herniation. Numerous studies have confirmed its significant efficacy and advantages in managing ovarian insufficiency diseases， including diminished ovarian reserve （DOR）， premature ovarian insufficiency （POI）， and premature ovarian failure （POF）. According to recent literature， the therapeutic mechanisms of GSW in treating ovarian insufficiency diseases involve regulating the hypothalamic-pituitary-ovarian axis （HPOA） function， ameliorating reproductive endocrine disorders， improving ovarian function， modulating relevant signaling pathways， and exerting immunoregulatory and anti-inflammatory effects. A review of GSW in clinical treatment revealed that clinical applications of GSW， particularly in combination with Western medicine， not only alleviate symptoms but also compensate for the limitations of hormone replacement therapy， thereby reducing recurrence， minimizing adverse reactions， and enhancing safety. This review aims to provide a scientific basis for the rational clinical use of GSW in ovarian insufficiency diseases， offer innovative TCM strategies for developing novel ovarian-protective drugs， promote the integration of TCM and Western medicine in reproductive medicine， and ultimately contribute a Chinese approach to global management of ovarian insufficiency diseases.

AIM: To compare the diagnostic efficiency of binocular uncorrected distance visual acuity(UCDVA), pre-cycloplegia refraction spherical equivalent(PR-SE), axial length(AL)difference, and their different combinations in the screening of anisometropia in children and adolescents, and to evaluate the practical value of different indicator combinations in simplifying the screening process when taking cycloplegic retinoscopy results as the gold standard for diagnosing anisometropia.METHODS: This was a retrospective study. A total of 500 consecutive cases of children and adolescents aged 6-18 years with known refractive status were included. Taking cycloplegic retinoscopy results as the gold standard for anisometropia diagnosis, the binocular UCDVA, PR-SE, and AL difference were incorporated into ROC curve analysis to assess the diagnostic efficacy of each indicator. Furthermore, predictive models were constructed and reliability analysis was performed.RESULTS: The average age of the included cases was 10.75±2.24 years, including 239 males and 261 females. The AUC of the interocular PR-SE difference(0.972, 95%CI: 0.960-0.984)was significantly higher than that of other indicators. The Youden index was the largest when the bincular UCDVA difference was 0.25, the PR-SE difference was 0.743, and the AL difference was 0.31. When the interocular PR-SE difference used 0.743 and 1.00 D as screening cutoffs, the former had a higher AUC(AUC=0.924, 95%CI: 0.895-0.953). Comparison of different constructed predictive models showed that when the binocular PR-SE difference was ≥0.743 D, the negative predictive value reached 98.89%, making it suitable for initial screening. The combination of UCDVA+PR-SE+AL had the highest specificity and positive predictive value, while the PR-SE+AL combination had the highest consistency rate.CONCLUSION: The binocular PR-SE difference is the best choice for single-indicator screening. Combining UCDVA and AL can increase the specificity to 98.00% and the positive predictive value to 88.24%. The PR-SE+AL combination can achieve the highest consistency rate.

Diabetic dry eye is a prevalent ocular surface disease and has a profound impact on patients'quality of visual acuity.The pathological changes of diabetic dry eye are influenced by a multitude of factors,involving the effects of hyperglycemia on the ocular surface microenvironment and corneal nerves,oxidative stress and the accumulative effect of glycation end products.Current therapeutic strategies include physiotherapy,tear replacement therapy,promotion of ocu-lar surface repair,and anti-inflammatory therapy.However,these treatments have certain limitations.This article presents a summary of the research conducted on the pathogenesis and clinical treatment of diabetic dry eye in recent years,aiming to provide clinicians with new ideas for developing personalized treatment plans for diabetic dry eye patients.

Objective:To explore the application effect of the teaching method combining process-oriented-guided inquiry learning (POGIL) theory and micro-class in orthopedic clinical internship.Methods:The 118 interns who completed internship from January 2022 to December 2022 were randomly divided into a control group (58) and an experimental group (60). The control group received traditional teaching, while the experimental group received a teaching method combining POGIL theory and micro-class. After the internship, the two groups were compared for assessment scores (basic theoretical knowledge and professional theoretical knowledge), learning status (classroom performance and self-learning ability), clinical practice ability (Leicester Assessment Scale), and teaching satisfaction. The t-test and chi-square test were performed using SPSS 21.0. Results:After the internship, the assessment scores, classroom performance, self-directed learning ability scores, clinical skills, case writing scores, and teaching satisfaction of the experimental group were all higher than those of the control group ( t/ χ2=5.01, 3.72, 2.20, 6.57, 3.56, 4.52, P<0.05). Conclusions:The teaching method combining POGIL theory and micro-class can enhance the master of theoretical knowledge by orthopedic interns, optimize classroom performance, cultivate self-learning ability, and improve clinical practice ability and teaching satisfaction.

Objective:To evaluate the effect of heavy smoking on the dose-effect relationship of ciprofol for painless gastroscopy when combined with alfentanil.Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ male patients, aged 18-64 yr, with body mass index of 18-28 kg/m 2, undergoing elective painless gastroscopy from October 2023 to February 2024 in Baoding First Central Hospital, were divided into non-smoking group and heavy smoking group (smoking index>400) according to the status of smoking. Alfentanil 5 μg/kg and ciprofol were intravenously injected, and gastroscopy was performed after the patient′s eyelash reflex disappeared and the jaw was relaxed. The study was performed by the Dixon′s up-and-down method, and the initial dose of ciprofol was 0.4 mg/kg. The dose of ciprofol increased or decreased by 0.04 mg/kg each time based on the positive or negative response of the previous patient. A positive response was defined as the Modified Observer′s Assessment of Alertness/Sedation Scale score being greater than 1 point at 3 min after ciprofol injection or the occurrence of coughing, swallowing, body movement, or other responses that affected the operation during the insertion of the endoscope. The median effective dose (ED 50) and 95% confidence interval of propofol for painless gastroscopy were determined by the probit analysis. Results:Twenty-five patients were finally included in non-smoking group and 23 patients in heavy smoking group. The ED 50 (95% confidence interval) of ciprofol when combined with alfentanil was 0.205 (0.159, 0.244) mg/kg in non-smoking group and 0.252 (0.184, 0.295) mg/kg in heavy smoking group. The ED 50 was significantly higher in heavy smoking group than in non-smoking group ( u=390, P=0.009). Conclusions:Heavy smoking can weaken the sedative potency of propofol for sedation when used for painless gastroscopy when combined with alfentanil.

Objective:To evaluate the effect of age on the sedative potency of remimazolam.Methods:This was a prospective study. Patients of either sex, aged 40-80 yr, with body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective surgery with general anesthesia, were divided into middle age group (40-64 yr) and elderly group (65-80 yr) based on the age of the patients. The test was performed by the Dixon′s up-and-down method. The initial dose of remimazolam was 0.3 mg/kg. The Modified Observer′s Assessment of Alertness/Sedation Scale score ≤1 and bispectral index value≤60 within 3 min after administration were considered as an effective sedation. The dose of remimazolam was increased/decreased by 0.03 mg/kg based on the sedative efficacy in the previous patient. The 50% effective dose (ED 50) and 95% confidence interval ( CI) of remimazolam were calculated by the probit method. The time to the loss of consciousness was recorded. Results:The ED 50 (95% CI) of remimazolam was 0.345 (0.306-0.384) mg/kg in middle age group, while the ED 50 (95% CI) of remimazolam was 0.322 (0.303-0.339) mg/kg in elderly group. The ED 50 was significantly higher in middle age group than in elderly group ( u=417.00, P=0.022). The time to loss of consciousness was significantly longer in elderly group than in middle age group ( t=-2.96, P=0.008). Conclusions:For middle-aged and elderly patients aged 40-80 yr, the sedative potency of remimazolam increases with age.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective:To investigate the impact of the early infusion rate on prognosis and the factors of influencing the infusion rate in patients with severe burns and inhalation injury.Methods:This study was a retrospective case series research. From January 2015 to December 2020, 220 patients with severe burns and inhalation injury meeting the inclusion criteria were admitted to 7 burn treatment centers in China, including 13 cases in the Fourth People's Hospital of Dalian, 26 cases in the First Affiliated Hospital of Naval Medical University, 73 cases in Guangzhou Red Cross Hospital of Jinan University, 21 cases in the 924 th Hospital of PLA, 30 cases in the First Affiliated Hospital of Jiangxi Medical College of Nanchang University, 30 cases in Tongren Hospital of Wuhan University & Wuhan Third Hospital, and 27 cases in Zhengzhou First People's Hospital. There were 163 males and 57 females, and their ages ranged from 18 to 91 years. The patients were divided into survival group and death group according to the survival within 28 d post injury. The following data of patients in the 2 groups were collected, including basic information (gender, age, body weight, body temperature, etc.), the injury characteristics (total burn area, post-injury admission time, etc.), the underlying diseases, the post-injury fluid resuscitation condition (infusion rate and ratio of infused electrolyte solution to colloid solution in the first 24 h post injury, etc.), the results of laboratory tests on admission (blood urea nitrogen, blood creatinine, albumin, pH value, base excess, blood lactate, oxygenation index, etc.), and treatment condition (inhaled oxygen volume fraction, hospitalization day, renal replacement therapy, etc.). After adjusting covariates using univariate Cox regression analysis, the multivariate Cox regression analysis was performed to evaluate the impact of infusion rate in the first 24 h post injury on patient death. The receiver operator characteristic curve for the infusion rate in the first 24 h post injury to predict the risk of death was plotted, and the maximum Youden index was calculated. Patients were divided into 2 groups according to the cutoff value (2.03 mL·kg -1·% total body surface area (TBSA) -1) for predicting risk of death by the infusion rate in the first 24 h post injury determined by the maximum Youden index, and the risk of death was compared between the 2 groups. The correlation between the previously mentioned clinical data and the infusion rate in the first 24 h post injury was analyzed; after the univariate linear regression analysis was used to screen the independent variables, the multivariate linear regression analysis was performed to screen the independent influential factors on the infusion rate in the first 24 h post injury. Results:Compared with those in survival group, patients in death group had significantly higher age and total burn area (with Z values of 12.08 and 23.71, respectively, P<0.05), the infusion rate in the first 24 h post injury, inhaled oxygen volume fraction, and blood urea nitrogen, blood creatinine, blood lactic acid on admission (with Z values of 7.99, 4.01, 11.76, 23.24, and 5.97, respectively, P<0.05), and the proportion of patients treated with renal replacement therapy ( P<0.05) were significantly higher, the albumin, pH value, and base excess on admission were significantly lower ( t=2.72, with Z values of 8.18 and 9.70, respectively, P<0.05), and the hospitalization day was significantly reduced ( Z=85.47, P<0.05). After adjusting covariates, the infusion rate in the first 24 h post injury was the independent influential factor on death (with standardized hazard ratio of 1.69, 95% confidence interval of 1.21-2.37, P<0.05). Patients in infusion rate ≥2.03 mL·kg -1·%TBSA -1 group had a significantly higher risk of death than those in infusion rate <2.03 mL·kg -1·% TBSA -1 group (with hazard ratio of 3.47, 95% confidence interval of 1.48-8.13, P<0.05). There was a significant correlation between total burn area, body weight, inhaled oxygen volume fraction, body temperature, post-injury admission time, the ratio of infused electrolyte solution to colloid solution in the first 24 h post injury, and oxygenation index <300 on admission and the infusion rate in the first 24 h post injury (with r values of -0.192, -0.215, 0.137, -0.162, -0.252, and 0.314, respectively, Z=4.48, P<0.05). After screening the independent variables, total burn area, body weight, post-injury admission time, and oxygenation index <300 on admission were the independent influential factors on the infusion rate in the first 24 h post injury (with standardized β values of -0.22, -0.22, -0.19, and 0.46, respectively, 95% confidence intervals of -0.34 to 0.09, -0.34 to 0.10, -0.32 to 0.06, and 0.22 to 0.71, respectively, P<0.05). Conclusions:The infusion rate in the first 24 h post injury in patients with severe burns and inhalation injury is the independent factor of influencing death, and patients with infusion rate ≥2.03 mL·kg -1·%TBSA -1 in the first 24 h post injury have a significantly increased risk of death. The total burn area, body weight, post-injury admission time, and oxygenation index <300 on admission were the independent factors of influencing the infusion rate in the first 24 h post injury in patients with severe burns and inhalation injury.

Objective:To discuss the biological function of the spacer domain of ADAM metalloproteinase with thrombospondin type 1 motifs 13(ADAMTS13)in the cleaving process of von Willebrand factor(vWF),and to clarify the role of ADAMTS13 in the pathogenesis of thrombotic thrombocytopenic purpura(TTP).Methods:The point mutation method was introduced sequentially into the amino acid residues TEDRLPR of the ADAMTS13 spacer domain(mutants M1-M7)by site-directed mutagenesis.The constructed ADAMTS13 and its mutants plasmids were transfected into the human embryonic kidney HEK293 cells,and the recombinant proteins were purified after stable expression.The cleavage capabilities of both wild type and mutant ADAMTS13 were observed under denaturation conditions,shear stress,and after treatment with ADAMTS13 antibodies.Results:The fluorescence resonance energy transfer(FRET)assay results showed that compared with wild type ADAMTS13,the cleavage abilities of ADAMTS13 mutant M4(R635A)and mutant M7(R638A)on the FRET-vWF73 were decreased(P＜0.05).Under denaturation conditions,the wild-type ADAMTS13 could cleave the vWF multimers;compared with wild-type ADAMTS13,the cleavage activities of ADAMTS13 mutant M4(R635A)and mutant M7(R638A)were significantly decreased(P＜0.01).Under in vitro shear stress,compared with wild type ADAMTS13,the abilities of ADAMTS13 mutant M4(R635A)and mutant M7(R638A)to cleave vWF multimers were significantly decreased(P＜0.01).Compared with wild type ADAMTS13,the binding affinity between vWF and ADAMTS13 mutant M4(R635A)and mutant M7(R638A)had no significant difference(P＞0.05),indicating there were multiple binding sites between C-terminal of ADAMTS13 and vWF.The ADAMTS13 antibodies were able to inhibit the cleavage ability of both wild-type and mutant ADAMTS13 to some extent.Conclusion:The activity of ADAMTS13 after spacer domain mutation is decreased.The ADAMTS13 mutant M4(R635A)and mutant M7(R638A)may be the important action sites for AD AMTS 13 in substrate recognition.