ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

Objective:To investigate the risk factors associated with post-prematurity respiratory disease (PPRD) in very preterm infants.Methods:A prospective cohort study was conducted, enrolling 369 very preterm infants who were admitted to the neonatal intensive care unit of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, within one week of birth from January 2019 to June 2023. Data on maternal and infant clinical characteristics, neonatal morbidities, and treatments during hospitalization were collected. The very preterm infants were divided into 2 groups based on whether they developed PPRD. Continuous variables were compared using Mann-Whitney U test, while categorical variables were compared using χ2 tests or continuity correction χ2 test. Multivariate Logistic regression analysis was used to identify the independent risk factors for PPRD in very preterm infants. Results:Among the 369 very preterm infants, 217 cases(58.8%) were male, with a gestational age of 30 (28, 31) weeks at birth and a birth weight of 1 320 (1 085, 1 590) g. Of these, 116 cases (31.4%) developed PPRD, while 253 cases (68.6%) did not. The very preterm infants in the PPRD group had a lower gestational age and lower birth weight (both, P<0.001). The PPRD group also had a higher proportion of males, lower Apgar scores at the 1 th minute after birth and the 5 th minutes after birth, a higher rate of born via cesarean delivery, and a higher incidence of bronchopulmonary dysplasia, more pulmonary surfactant treatment, longer durations of mechanical ventilation, longer total oxygen therapy, and lower Z-score for weight at discharge (all P<0.05). Multivariate Logistic regression analysis showed that gestational age ( OR=0.85, 95% CI 0.73-0.99, P=0.037), born via cesarean delivery ( OR=2.23, 95% CI 1.21-4.10, P=0.010), a duration of mechanical ventilation ≥7 days ( OR=2.51, 95% CI 1.43-4.39, P=0.001), and a Z-score for weight at discharge ( OR=0.82, 95% CI 0.67-0.99, P=0.040) were all independent risk factors for PPRD in very preterm infants. Conclusion:Very preterm infants with a small gestational age, born via cesarean section, mechanical ventilation ≥7 days, and a low Z-score for weight at discharge should be closely monitored for PPRD, and provided with standardized respiratory management after discharge.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

BackgroundMany studies have shown that patients with depressive disorder show impairments in prospective memory， while it is deemed necessary for facilitating their social reintegration， and the current research findings are inconsistent regarding the factors affecting prospective memory of patients with depressive disorder. ObjectiveTo explore the impact of target characteristics （emotional valence and salience） on prospective memory in patients with depressive disorder， so as to provide references for the training and recovery of prospective memory function in these patients. MethodsFrom January to December 2022， 53 patients with depressive disorder were recruited from the outpatient department of Inner Mongolia Autonomous Mental Health Center. Meanwhile， 45 healthy individuals were concurrently recruited from surrounding communities as control group. An experiment with a 2 （participant type： depressive disorder， healthy control） ×2 （target salience： salient， non-salient） ×3 （emotional valence： positive， neutral， negative） factorial design was conducted. The positive/neutral/negative emotional pictures from Chinese Affective Picture System （CAPS） were used for emotional stimulation. A dual-task experimental paradigm was adopted， and the response time and accuracy in prospective memory task and ongoing task were recorded for participants with different target characteristics. Results①In the prospective memory task， the main effect of participant type was statistically significant， with the depressive group showing lower accuracy （F=14.892， P<0.01） and longer response time （F=10.642， P=0.002） compared with control group. ② The main effect of target emotional valence on accuracy （F=7.575， P=0.001） and response time （F=3.196， P=0.044） in the prospective memory task was statistically significant. Simple effect analysis revealed that depressive group yielded a shorter response time and higher accuracy rate under negative conditions compared with positive and neutral conditions （P<0.05 or 0.01）. ③ The main effect of target salience on accuracy （F=6.659， P=0.012） and response time （F=10.106， P=0.002） in the prospective memory task was also statistically significant， with higher accuracy and shorter response time for salient targets compared with non-salient targets. ConclusionPatients with depressive disorder demonstrate preferential attention to and processing of negative stimuli in prospective memory tasks， while increasing target salience may facilitate spontaneous processing of prospective memory task in patients with depressive disorder. ［Funded by Inner Mongolia Health Commission Medical Health Science and Technology Project （number， 202202104）］

Due to the poor ionization efficiency and the weak mass spectrometry(MS)intensity of weakly polar substances,direct analysis using the traditional electrospray ionization mass spectrometry(ESI-MS)is a big challenge.In this study,a novel rapid on-site detection method of four prohibited sex hormones in cosmetics was proposed using online derivatization strategy coupled with a miniature mass spectrometer.The target substances in the samples were extracted by a custom-made polyaniline/multi-walled carbon nanotube solid-phase microextraction(SPME)probe.The stirring speed was 200 r/min,the extraction temperature was 40℃,and the extraction time was 2 min.A pulled dual-channel θ borosilicate glass capillary emitter was used as the nano-ESI ion source.The SPME probe was inserted into the channel containing methanol in theθborosilicate glass capillary.When the spray voltage was applied,the four sex hormones were desorbed and formed spray microdroplets,which then collided with the hydroxylamine microdroplets generated from the other channel.The microdroplets of reaction product entered into the miniature mass spectrometer for direct analysis.The limits of detection(LOD)and limits of quantification(LOQ)for the four sex hormones were 10-20 ng/mL and 20-50 ng/mL,respectively.The recoveries were from 84.6%to 107.8%with the relative standard deviations(RSD)from 4.1%to 11.6%.Compared to detection without derivatization,the MS signals of the four target substances were increased by 3 to 15 times.This method was simple,rapid,highly efficient and sensitive,and suitable for on-site rapid analysis of weakly polar sex hormones in cosmetics.

The term yin excess originated in the Huang Di Nei Jing, which refers to the phenomenon of "heavy yin" when wind pathogens invades the human body and defensive qi enters the yin part of the human body. Later doctors have played a role in yin excess. Theoretically, yin and yang are out of balance in the human body, and yin is too much and yang is not enough, which is the process of physiological transformation to pathology; from the diagnosis point of view, patients with yin deficiency have less pulse and more blood; from the clinical manifestations, patients with yin excess appear cold from the back, hands and feet cold reverse; from the point of view of treatment, bitter cold products can cause yin excess. Modern research specifies yin as phlegm, dampness, stasis and other pathological products, and emphasize the relation between yin excess and yang deficiency. Yin excess includes pathological factors such as phlegm stasis cold, external cold straight in the liver wood, set in the hypochasm, resulting in mass; or overthinking and cold drink injury spleen, phlegm turbidiousness, long and hard phlegm forming lumps, thus resulting yin excess; or it may deplete the yang energy of the heart, leading to neglect of the warming function and stagnation of blood stasis; or if the kidney yang is deficient and the body lacks warmth, and there is no true yang in the ridge, then the wood will sink and congest blood stasis; the above etiology and pathogenesis lead to the occupation of yin pathogens, resulting in liver cancer. The treatment methods include liver cold turbidizing, warming liver and dispelling cold, with Wuzhuyu Decoction; spleen-deficiency phlegm production, the treatment should be warm the middle and resolving the phlegm, with Linggui Zhugan Decoction and Zhenwu Decoction; Yang deficiency and stasis, the treatment should warm kidney to remove blood stasis, with Poyu Decoction.