bjective To analyze the growth trends of height and weight among primary and secondary school students, and explore the developmental characteristics and gender differences at different age groups, and to provide a scientific basis for adolescent health policy formulation. Methods Based on 675 175 health examination records of 227 978 students aged 6-17 years in Shiyan City from 2015 to 2024, a logistic growth model was employed to fit the curves of height and weight changes with age. Results From 2015 to 2024, height and weight showed steady increases across all age groups, exhibiting typical sigmoidal growth patterns. The growth rates varied across age groups: the younger age group (6-9 years) showed a moderate growth (annual height increase of 0.5-1.0 cm, weight increase of 0.03-0.06 kg/year), while the older age group (10-17 years) demonstrated a significant growth (annual height increase of 1.5-2.0 cm, weight increase of 0.22-0.38 kg/year). The growth rate curves displayed a unimodal distribution. The growth inflection points of male students occurred later than that of female students (height inflection point: 9.87 years for males vs. 8.98 years for females; weight inflection point: 10.70 years for males vs. 9.99 years for females). Female students experienced a more concentrated but shorter period of growth and development. The peak height growth rate was 7.40 cm/year at age 9 for females and 7.09 cm/year at age 10 for males, while the peak weight growth rate was 5.04 kg/year at age 10 for females and 5.27 kg/year at age 11 for males. Conclusion The physical development of primary and secondary school students in Shiyan City follows a logistic growth pattern, with significant gender differences and characteristics of adolescent growth spurts. Female students exhibit an earlier and more concentrated growth process.

Objective:To evaluate the toxicity of foscarnet sodium injection into the anterior chamber and intravitreal cavity on the cornea and retina.Methods:Thirty-six adult New Zealand White rabbits were randomly divided into control group, intravitreal injection group, and intracameral injection group, with 12 rabbits in each group.In the control group, 0.1 ml of balanced salt solution (BSS) was injected into the vitreous cavity of one eye, and an equal volume of BSS was injected into the anterior chamber of the other eye.In the intracameral injection group and intravitreal injection group, 0.1 ml of sodium foscarnet 1.2 mg was injected into the anterior chamber and vitreous cavity of one eye, respectively.Slit-lamp microscopy, ophthalmoscope, optical coherence tomography (OCT), and in vivo confocal laser scanning microscopy were performed on 3 experimental rabbits from each group on days 1, 7, 14, and 28 after injection.After sacrifice, both eyeballs were removed, and the corneas and retinas were examined using optical microscopy, scanning electron microscopy and transmission electron microscopy to evaluate the toxicity to the cornea and retina comprehensively.The use and care of the animals complied with the ARVO Statement.The study protocol was approved by an Ethics Committee of Peking University Third Hospital (No.IRB00006761-2015197). Results:Slit-lamp microscopy and OCT showed no corneal edema, intraocular inflammation, or other abnormalities in the intravitreal injection and control groups.Mild corneal edema was observed in intracameral injection group 1 day after injection, which resolved 7 days after injection. In vivo confocal laser scanning microscopy revealed normal hexagonal corneal endothelial cell morphology in the intravitreal injection and control groups.There was no significant difference in endothelial cell density at baseline and 1, 7, and 14 days after injection among the three groups ( Fgroup=1.21, P=0.32; Ftime=1.21, P=0.32).Light microscopy revealed no obvious corneal abnormalities.On days 1 and 7 after injection, retinal nerve fiber layer vacuolization and inflammatory cell infiltration were observed in the intravitreal injection and control groups.In the intravitreal injection of BSS group, inflammatory cell infiltration occurred in the retina without vacuolization 1 day after injection.There were no structural changes in the photoreceptor layer, and the nuclear layer was well-organized.Scanning electron microscopy showed no significant abnormalities in the corneal endothelium in the intravitreal injection group 1 day after injection.In the intracameral injection group, a large number of inflammatory cells were deposited and adhered to the corneal endothelium 1 day after injection and disappeared 7 days after injection.Transmission electron microscopy revealed that in the intravitreal injection group, 1 day after injection swelling of corneal endothelial cells, dilatation of the endoplasmic reticulum, and partial mitochondrial swelling were observed, which normalized 14 days after injection and vacuolization was present in the retina and interstitial fluid accumulation persisted until the 28 days after injection.In the intracameral injection group, swollen mitochondrial and endoplasmic reticulum of corneal endothelial cells was observed and resolved by 14 days after injection.However, structural abnormalities in the membranous discs of the photoreceptor outer segments and interstitial fluid accumulation in the optic nerve fiber layer persisted 1 day after injection and did not fully recover 28 days after injection. Conclusions:Intracameral intravitreal and injection of foscarnet sodium have transient toxic effects on the retina, which gradually weaken over time.Intracameral injection of foscarnet sodium was more toxic to corneal endothelial cells than intravitreal injection.

Objective:To analyze the risk factors of poor prognosis in older adult patients with acute respiratory failure (ARF) induced by septic shock.Methods:A retrospective analysis was performed on the clinical data of 146 patients with ARF induced by septic shock who received treatment at Lishui Central Hospital between January 2020 and December 2022. According to prognosis, these patients were divided into a good prognosis group and a poor prognosis group. The factors that affect the prognosis were analyzed by regression analysis.Results:Among the 146 patients, there were 102 cases (69.86%) with a good prognosis and 44 cases (30.14%) with a poor prognosis. The incidence of multidrug-resistant bacterial infections and the Murray lung injury score in the poor prognosis group were 54.54% (24/44) and (2.11 ± 1.02), respectively, both of which were significantly higher than those in the good prognosis group [23.53% (24/102), (3.29 ± 0.12), χ2 = 13.40, t = 7.63, both P < 0.001]. In the poor prognosis group, the usage rate of beta-blockers was 34.09% (15/44), while oxygenation index and serum levels of albumin and Ca 2+ were (211.32 ± 44.56) mmHg (1 mmHg = 0.133 kPa), (27.02 ± 5.21) g/L, and (2.19 ± 0.25) mmol/L, respectively. These values were significantly lower than those in the poor prognosis group [63.73% (65/102), (257.46 ± 49.65) mmHg, (30.57 ± 5.45) g/L, (2.52 ± 0.31) mmol/L, χ2 = 10.89, t = 5.54, 3.65, 6.23, all P < 0.001]. An increased Murray lung injury score, the presence of multidrug-resistant bacterial infections, and decreased serum levels of Ca 2+ and albumin were independent risk factors for poor prognosis in patients with ARF induced by septic shock ( OR = 1.958, 2.100, 2.147, 2.098, all P < 0.05). Conversely, the use of beta-blockers was identified as a protective factor for prognosis ( OR = 0.480, P = 0.025). Conclusions:Multidrug-resistant bacterial infections, low oxygenation index, and decreased serum levels of Ca 2+ and albumin are independent risk factors for poor prognosis in patients with ARF induced by septic shock. Conversely, the use of beta-blockers serves as a protective factor for prognosis.

Objective:To evaluate the toxicity of foscarnet sodium injection into the anterior chamber and intravitreal cavity on the cornea and retina.Methods:Thirty-six adult New Zealand White rabbits were randomly divided into control group, intravitreal injection group, and intracameral injection group, with 12 rabbits in each group.In the control group, 0.1 ml of balanced salt solution (BSS) was injected into the vitreous cavity of one eye, and an equal volume of BSS was injected into the anterior chamber of the other eye.In the intracameral injection group and intravitreal injection group, 0.1 ml of sodium foscarnet 1.2 mg was injected into the anterior chamber and vitreous cavity of one eye, respectively.Slit-lamp microscopy, ophthalmoscope, optical coherence tomography (OCT), and in vivo confocal laser scanning microscopy were performed on 3 experimental rabbits from each group on days 1, 7, 14, and 28 after injection.After sacrifice, both eyeballs were removed, and the corneas and retinas were examined using optical microscopy, scanning electron microscopy and transmission electron microscopy to evaluate the toxicity to the cornea and retina comprehensively.The use and care of the animals complied with the ARVO Statement.The study protocol was approved by an Ethics Committee of Peking University Third Hospital (No.IRB00006761-2015197). Results:Slit-lamp microscopy and OCT showed no corneal edema, intraocular inflammation, or other abnormalities in the intravitreal injection and control groups.Mild corneal edema was observed in intracameral injection group 1 day after injection, which resolved 7 days after injection. In vivo confocal laser scanning microscopy revealed normal hexagonal corneal endothelial cell morphology in the intravitreal injection and control groups.There was no significant difference in endothelial cell density at baseline and 1, 7, and 14 days after injection among the three groups ( Fgroup=1.21, P=0.32; Ftime=1.21, P=0.32).Light microscopy revealed no obvious corneal abnormalities.On days 1 and 7 after injection, retinal nerve fiber layer vacuolization and inflammatory cell infiltration were observed in the intravitreal injection and control groups.In the intravitreal injection of BSS group, inflammatory cell infiltration occurred in the retina without vacuolization 1 day after injection.There were no structural changes in the photoreceptor layer, and the nuclear layer was well-organized.Scanning electron microscopy showed no significant abnormalities in the corneal endothelium in the intravitreal injection group 1 day after injection.In the intracameral injection group, a large number of inflammatory cells were deposited and adhered to the corneal endothelium 1 day after injection and disappeared 7 days after injection.Transmission electron microscopy revealed that in the intravitreal injection group, 1 day after injection swelling of corneal endothelial cells, dilatation of the endoplasmic reticulum, and partial mitochondrial swelling were observed, which normalized 14 days after injection and vacuolization was present in the retina and interstitial fluid accumulation persisted until the 28 days after injection.In the intracameral injection group, swollen mitochondrial and endoplasmic reticulum of corneal endothelial cells was observed and resolved by 14 days after injection.However, structural abnormalities in the membranous discs of the photoreceptor outer segments and interstitial fluid accumulation in the optic nerve fiber layer persisted 1 day after injection and did not fully recover 28 days after injection. Conclusions:Intracameral intravitreal and injection of foscarnet sodium have transient toxic effects on the retina, which gradually weaken over time.Intracameral injection of foscarnet sodium was more toxic to corneal endothelial cells than intravitreal injection.

Objective:To analyze the risk factors of poor prognosis in older adult patients with acute respiratory failure (ARF) induced by septic shock.Methods:A retrospective analysis was performed on the clinical data of 146 patients with ARF induced by septic shock who received treatment at Lishui Central Hospital between January 2020 and December 2022. According to prognosis, these patients were divided into a good prognosis group and a poor prognosis group. The factors that affect the prognosis were analyzed by regression analysis.Results:Among the 146 patients, there were 102 cases (69.86%) with a good prognosis and 44 cases (30.14%) with a poor prognosis. The incidence of multidrug-resistant bacterial infections and the Murray lung injury score in the poor prognosis group were 54.54% (24/44) and (2.11 ± 1.02), respectively, both of which were significantly higher than those in the good prognosis group [23.53% (24/102), (3.29 ± 0.12), χ2 = 13.40, t = 7.63, both P < 0.001]. In the poor prognosis group, the usage rate of beta-blockers was 34.09% (15/44), while oxygenation index and serum levels of albumin and Ca 2+ were (211.32 ± 44.56) mmHg (1 mmHg = 0.133 kPa), (27.02 ± 5.21) g/L, and (2.19 ± 0.25) mmol/L, respectively. These values were significantly lower than those in the poor prognosis group [63.73% (65/102), (257.46 ± 49.65) mmHg, (30.57 ± 5.45) g/L, (2.52 ± 0.31) mmol/L, χ2 = 10.89, t = 5.54, 3.65, 6.23, all P < 0.001]. An increased Murray lung injury score, the presence of multidrug-resistant bacterial infections, and decreased serum levels of Ca 2+ and albumin were independent risk factors for poor prognosis in patients with ARF induced by septic shock ( OR = 1.958, 2.100, 2.147, 2.098, all P < 0.05). Conversely, the use of beta-blockers was identified as a protective factor for prognosis ( OR = 0.480, P = 0.025). Conclusions:Multidrug-resistant bacterial infections, low oxygenation index, and decreased serum levels of Ca 2+ and albumin are independent risk factors for poor prognosis in patients with ARF induced by septic shock. Conversely, the use of beta-blockers serves as a protective factor for prognosis.

Objective:To investigate the effect of programmed blood glucose management model on blood glucose control and prognosis in patients with sepsis and diabetes mellitus.Methods:Seventy-six patients with sepsis and diabetes mellitus who received treatment at the Fifth Hospital Affiliated to Wenzhou Medical University (Lishui Central Hospital) were included in this study. According to the implementation time of programmed blood glucose management model, the patients were divided into a routine group ( n = 37; receiving routine nursing between January 2021 and December 2022) and an experimental group ( n = 39, receiving routine nursing and programmed blood glucose management). Length of hospital stay, 28-day mortality rate, blood glucose control level (glycosylated hemoglobin level, blood glucose variability, incidence of hypoglycemia, fasting blood glucose level, and 2-hour postprandial glucose level), and health status (Medical Outcomes Study-36-Item Shot-Form Health Status Survey) as well as incidence of adverse events were compared between the two groups. Results:The length of hospital stay in the experimental group was (14.85 ± 2.77) days, which was significantly shorter than that in the routine group [(17.42 ± 3.24) days, t = 3.72, P < 0.001]. The 28-day mortality rate in the experimental group was 7.69% (3/39), which was significantly lower than that in the control group [24.32% (9/37), χ2 = 3.95, P = 0.047]. The level of glycated hemoglobin and blood glucose variability in the experimental group were 10.4 (8.5, 12.1) mmol/L and (31.54 ± 7.16)%, which were significantly lower than those in the routine group [12.8 (8.9, 15.3) mmol/L, (45.63 ± 12.19)%, Z = 6.88, P < 0.001; t = 6.18, P < 0.001]. There was no significant difference in the incidence of hypoglycemia between the experimental and routine groups [10.81% (4/37) vs. 5.13% (2/39), χ2 = 0.84, P = 0.358]. After the intervention, the experimental group had higher scores in various dimensions of the 36-Item Shot-Form Health Status Survey, including limitations [(72.21 ± 5.37) points], bodily pain [(82.98 ± 6.41) points], general health [(81.32 ± 6.23) points], and physical function [(71.43 ± 5.22) points] compared with the routine group [(68.39 ± 6.21) points, (78.35 ± 6.17) points, (74.50 ± 7.57) points, (65.57 ± 6.96) points, t = 2.87, P = 0.005; t = 3.20, P = 0.002; t = 4.29, P < 0.001; t = 4.16, P < 0.001]. There was no significant difference in the incidence of adverse events between the experimental and routine groups [10.26% (4/39) vs. 13.51% (5/37), χ2 = 0.19, P = 0.660]. Conclusion:Programmed blood glucose management model can improve blood glucose control level and prognosis of patients with sepsis and diabetes mellitus.

Objective:To investigate the clinical characteristics in older adult patients with sepsis and heart failure, and to analyze the influential factors of prognosis.Methods:Eighty-eight older adult patients with sepsis and heart failure who received treatment at Lishui Central Hospital from January 2020 to December 2022 were retrospectively included in the heart failure group. Eighty-eight older adult patients with sepsis, who did not have heart failure, were selected in a 1:1 ratio to form a non-heart failure group. Based on their survival status during hospitalization, the patients in the heart failure group were divided into two subgroups: the survival group and the death group. Logistic regression analysis was performed to identify the risk factors associated with the development of heart failure and adverse disease outcomes in older adult patients with sepsis.Results:There were no statistically significant differences in sex, smoking history, alcohol consumption history, history of hypertension, and history of diabetes between the heart failure group and the non-heart failure group (all P > 0.05). However, the proportion of patients aged 75 years or older in the heart failure group was 52.27% (46/88), which was significantly higher than the proportion in the non-heart failure group [34.09% (30/88), χ2 = 5.93, P < 0.05]. The proportion of patients with respiratory system infections in the heart failure group was 53.41% (47/88), which was significantly higher than the proportion in the non-heart failure group [29.55% (26/88), χ2 = 10.37, P < 0.05]. Logistic regression analysis showed that advanced age and respiratory system infections are independent risk factors for the development of heart failure in patients with sepsis. Among patients with sepsis and heart failure, 45 survived and 43 died, resulting in a mortality rate of 48.86%. The average age of patients in the death group was (76.27 ± 4.14) years, which was significantly higher than that in the survival group [(72.29 ± 4.06) years, t = 4.55, P < 0.05]. The brain natriuretic peptide level and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the death group were (636.70 ± 70.29) pg/mL and (31.93 ± 3.08) points, respectively, both of which were significantly higher than those in the survival group [(552.80 ± 54.66) pg/mL, (27.06 ± 3.80) points, t = 6.27, 6.59, both P < 0.05]. The lactate clearance rate and serum albumin level in the death group were (13.63 ± 4.84)% and (26.09 ± 4.77) g/L, respectively, both of which were significantly lower than those in the survival group [(19.94 ± 5.07)%, (30.55 ± 5.17) g/L, t = 5.97, 4.20, both P < 0.05]. Logistic regression analysis showed that in patients with sepsis and heart failure, advanced age, elevated serum brain natriuretic peptide levels, and high APACHE II scores are risk factors for poor prognosis and death. A high lactate clearance rate at 24 hours and elevated serum albumin levels are protective factors for survival. Conclusion:Advanced age and respiratory system infections increase the risk of heart failure in patients with sepsis. Advanced age, elevated brain natriuretic peptide levels, and high APACHE II scores are associated with an increased risk of death in these patients. High lactate clearance rates and elevated serum albumin levels are indicative of a reduced risk of death in patients with sepsis.

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Objective:To compare ocular surface dry eye-related indexes and tear cytokine level changes in chronic ocular graft-versus-host disease (oGVHD) patients after receiving topical treatment of 0.05% cyclosporine or 0.1% tacrolimus eye drops.Methods:A randomized controlled study was conducted.A total of 60 chronic oGVHD patients (60 eyes) were recruited at Beijing University Third Hospital from April 2020 to April 2021.The patients were divided into tacrolimus group and cyclosporine group by a random number table, with 30 patients (30 eyes) in each group.Patients in tacrolimus group used 0.1% tacrolimus eye drops (twice a day) and patients in cyclosporine group used 0.05% cyclosporine eye drops (4 times a day).Additionally, 0.1% flumetholon (twice a day), deproteinized calf blood extract (3 times a day), and 0.1% sodium hyaluronate eye drops (8 times a day) were applied for anti-inflammation and lubrication in both groups.Patients were screened according to exclusion criteria after 1-month treatment.Eventually, 21 patients (21 eyes) in tacrolimus group and 12 patients (12 eyes) in cyclosporine group were included for further study.Patients were examined before and 1 month after treatment.The primary evaluation indexes included Ocular Surface Disease Index (OSDI), corneal fluorescein staining scores and tear film break-up time (BUT).Expressions of interleukin (IL)-6, IL-8, IL-17, epidermal growth factor (EGF), and tumor necrosis factor-α (TNF-α) in tears were detected before and after treatment using Luminex chip.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University Third Hospital (No.M2020489).Written informed consent was obtained from each subject before any medical examination.Results:The OSDI differences between before and after treatment were 0.4(-5.6, 2.5) in tacrolimus group and 27.2(4.6, 45.0) in cyclosporine group, and the OSDI improvement was significantly greater in cyclosporine group than in tacrolimus group ( Z=-2.547, P=0.009).The differences of corneal fluorescein staining scores and BUT between before and after treatment were 5.0(2.5, 10.0) scores and 3.5(-0.5, 13.8) seconds in tacrolimus group, 0.0(-3.0, 0.0) scores and -1.5(-3.0, 0.0) seconds in cyclosporine group, respectively, with no significantly difference between both groups ( Z=-0.526, -0.804; both at P>0.05).The differences of IL-6, IL-8, IL-17, EGF and TNF-α expressions between before and after treatment in tacrolimus group and cyclosporine group were not significantly different ( Z=-0.487, -0.112, -0.412, -1.085, -1.198; all at P>0.05). Conclusions:Altered levels of all tested cytokines in oGVHD tears are of no significant differences between tacrolimus and cyclos porine treatment.In addition, 0.05% cyclosporine eye drops may be more comfortable than 1% tacrolimus for chronic oGVHD patients.

OBJECTIVE To introduce the construction of undergraduate specialty of clinical pharmacy based on the concept of outcome-based education （OBE），and to provide new idea and enlightenment for the construction of undergraduate specialty of clinical pharmacy in Chinese universities. METHODS Through the establishment and construction of training objectives and graduation requirements ，teaching reform was designed and implemented ，and the construction of teaching support system and teaching quality assurance system were completed. RESULTS The clinical pharmacy department of our university established the training direction of clinical pharmacy talents under the guidance of post competence ，including clarifying the training needs of undergraduate talents based on the overall requirements of national undergraduate education ；defining the social and industrial needs of clinical pharmacy talents based on the normative documents or concepts of clinical pharmacy ；clarifying the post and ability needs of clinical pharmacy talents based on the investigation of graduates and clinical pharmacists ；clarifying the development needs of clinical pharmacy based on the current situation and trends at home and abroad ；forming characteristic training objectives combined with the regional characteristics and school positioning ， so as to construct training objectives and graduation requirements. The OBE concept was introduced into the undergraduate teaching reform of clinical pharmacy ；the pharmacy talent training direction were established under the guidance of post competence ；the training system was designed by reverse design method；a training mode of both innovation and practical ability was built so as to promote teaching reform ，strengthen the construction of grass-roots teaching organizations and teaching staff ， and improve the construction of teaching quality assurance system. CONCLUSIONS The undergraduate training mode of clinical pharmacy specialty based on the concept of OBE is helpful to improve students ’personal comprehensive quality and professional knowledge and skills. The established undergraduate training model of clinical pharmacy specialty is in line with the modern educational concept and social needs ，and provides theoretical basis and practical experience for the training mode of clinical pharmacy professionals.