Background: and Purpose Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD). Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert’s syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al. Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41–2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43–2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45–2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson–Neyman analyses showed cut-off concentrations of 22.3–22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not. Conclusions Mildly elevated TBIL may modify the association between hypertension and CSVD.

Based on the theory of "cold qi generates turbidity" described in the Inner Canon of Yellow Emperor （《黄帝内经》）， together with the physiological characteristics of children， who are considered to have an inherent insufficiency of the lung， spleen， and kidney， and the clinical features of recurrent refractory nephrotic syndrome （RNS）， this article proposes that the pathogenesis of RNS in children is characterized by yang deficiency with internal cold， turbidity arising from cold， latent turbidity transforming into toxin， activation by newly contracted pathogens， and turbid toxins damaging the collaterals. The core pathogenesis is identified as yang deficiency， turbidity coagulation， and collateral damage. Accordingly， the general treatment principle is warming yang and eliminating turbidity， with coordination of three methods including warming yang to strengthen the body's foundation， promoting yang to relieve constraint， and raising yang while replenishing qi. Zhenwu Decoction （真武汤） is employed as the basic prescription with modification according to syndrome differentiation， to achieve an effect eliminating turbidity and arresting leakage， restoring kidney function by unblocking the collaterals， and consolidating recovery to prevent relapse.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

OBJECTIVE To explore the time windows for postoperative pneumonia in patients undergoing different surgeries,providing evidence-based references for optimizing infection monitoring and prevention and control strategies.METHODS Sociodemographic characteristics,clinical information and surgical details of 263 patients with postoperative pneumonia from four different types of medical institutions between Jan.2019 and Dec.2024 were retrospectively collected.The time windows for postoperative pneumonia in patients undergoing different surgeries were analyzed.RESULTS There were no statistically significant differences in the time windows for post-operative pneumonia among groups in terms of sociodemographic factors and underlying diseases.However,sta-tistically significant differences were observed in the time windows for postoperative pneumonia based on surgery type,incision type,surgical approach and surgery duration(P＜0.05).The average time for the onset of postop-erative pneumonia in 263 patients was 2.00(1.00,7.00)days.The postoperative time windows varied for sur-geries involving different systems.The peak incidence occurred on day 0(16 cases)and day 1(17 cases)af-ter neurological surgery,while the peak incidence for digestive system and orthopedic surgeries was on day 1.The time span for the onset of pneumonia after skin surgeries was wider(0-53 days postoperatively)without a clear peak.In addition,33.33％of cardiovascular system surgery cases developed pneumonia 10 days postoperatively.There were also significant time differences in the diagnostic elements of postoperative pneumonia,with fever and abnormal white blood cell counts appearing earlier(median appearance time length:4.00 days)than lung imaging changes(median appearance time length:7.00 days).CONCLUSIONS This study demonstrates significant time differences in the on-set of postoperative pneumonia and confirms the significant spatiotemporal heterogeneity in the diagnostic elements of postoperative pneumonia.These findings provide a quantitative basis for developing dynamic,surgery-type-spe-cific monitoring protocols and prevention and control measures for postoperative pneumonia.

Objective:To analyze the diagnostic value of inflammatory markers, clinical characteristics of patients with different prognoses, and variations in antimicrobial susceptibility testing for Klebsiella pneumoniae bloodstream infection. Methods:This study involved 166 patients with positive blood cultures for Klebsiella pneumoniae from January 2018 to May 2023 as the Klebsiella pneumoniae-positive group, and 100 patients with negative blood culture results as the negative group. The diagnostic value of inflammatory markers for Klebsiella pneumoniae bloodstream infection was evaluated through receiver operating characteristic (ROC) curve. The differences in C-reactive protein (CRP) and procalcitonin (PCT) levels between Klebsiella pneumoniae bloodstream infections and non- Klebsiella pneumoniae bloodstream infections were analyzed. According to the prognoses, 166 patients with Klebsiella pneumoniae bloodstream infection were divided into two groups: favorable outcome group (105 cases) and adverse outcome group (61 cases). Clinical features, infection sites, empirical use of antibiotics, and antimicrobial susceptibility were compared between the patients with different outcomes. Results:The percentage of neutrophils ( Z=-3.645, P<0.001), CRP level ( Z=-6.809, P<0.001), and PCT level ( Z=-8.214, P<0.001) were significantly higher in the Klebsiella pneumoniae-positive group than in the negative group. The area under the ROC curve (AUC) values for CRP and PCT in diagnosing Klebsiella pneumoniae bloodstream infection were 0.755 and 0.849, respectively. There were variations in CRP ( H=20.902, P<0.001) and PCT ( H=33.521, P<0.001) levels among patients with bloodstream infection caused by Klebsiella pneumoniae, other common negative bacilli, common positive cocci, or Candida. The body temperature, albumin level, hemoglobin level, and length of hospital stay in the adverse outcome group were lower than those in the favorable outcome group ( P<0.05). Besides, the incidence of invasive operation, organ failure, shock, and rescue were also lower in the adverse outcome group ( P<0.05). In the adverse outcome group, co-infections mainly involved respiratory infections, accounting for 60.7% (37/61). Respiratory infections (49.5%, 52/105) were also the predominant co-infections in the favorable outcome group, followed by hepatobiliary infections (34.3%, 36/105). The pathogenic bacteria cultured from different infection sites were mainly Klebsiella pneumoniae. In the favorable outcome group, fluoroquinolones were the most commonly used medications for empirical therapy, with a usage rate of 76.2% (80/105), followed by β-lactamase inhibitor complex preparations (68.6%, 72/105), the usage rate of which were significantly higher than those in the adverse outcome group ( P<0.05). Carbapenems were the preferred drugs for the adverse outcome group, with a usage rate of up to 62.3% (38/61), which was significantly higher than that in the favorable outcome group ( P<0.05). The adverse outcome group showed high resistance rates to ciprofloxacin (40.98%, 25/61) and levofloxacin (37.7%, 23/61), while the resistance rates were 22.86% (24/105) and 32.38% (34/105) in the favorable outcome group. The resistance rates to other drugs were low and there was no significant difference between the two groups ( P>0.05). Conclusions:PCT and CRP have certain value in diagnosing bloodstream infections caused by Klebsiella pneumoniae, and have certain reference significance for differentiating bloodstream infections caused by Gram-negative bacteria, Gram-positive bacteria, and Candida species. The source of bloodstream infection in patients with adverse outcome may be the respiratory system, while in patients with favorable outcome, the main sources of bloodstream infection may be the respiratory and hepatobiliary systems. Antimicrobial susceptibility testing reveals the highest resistance rate to fluoroquinolones. Given their frequent use in empirical therapy, this may lead to treatment failure. Notably, carbapenems are more commonly administered as empirical antibiotics in the adverse outcome group.

The blood products industry in China,the United States,the European Union and Japan are at different stages of development,with very different laws,regulations and regulatory systems.This paper uses methods such as literature review,policy comparison,and case study.By analyzing and comparing the blood product regulatory policies in various countries,it is found that compared with the United States,the European Union and Japan,China has differences in several areas,including plasma quarantine period,plasma fractionation processes and intermediate products,segmented production of blood products,and import management policies.It is suggested that we should learn from foreign regulatory experiences,and explore the establishment of blood product regulatory policies suitable for China's national conditions.Recommendations include optimizing China's source plasma quarantine period and blood product production process management policies,promoting multiple sites and segmented production of blood products,and establishing flexible blood product import and export management systems.These measures aim to provide references for promoting the development of the blood product industry and improving the accessibility of medications for the public.

Colorectal cancer （CRC） is a prevalent malignant tumor of the digestive tract， with a high incidence and high mortality. The majority of patients are diagnosed at the middle or advanced stage， which severely influences and threatens their physical health. Current treatment modalities such as surgery， radiotherapy， and chemotherapy often encounter challenges including metastasis， recurrence， and drug resistance. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway serves as a classical regulator that regulates physiological processes such as cell cycle， autophagy， apoptosis， and proliferation. Overexpression of this pathway is observed in various tumors. In the context of CRC， the activation of this pathway can facilitate the proliferation， invasion， and migration， inhibit the autophagy and apoptosis， promote the epithelial-mesenchymal transition of CRC cells， enhance angiogenesis within the tumor， and contribute to chemotherapy resistance and radiation resistance in CRC. Traditional Chinese medicine （TCM） treatment can exert an anti-CRC effect by inhibiting this pathway， thereby improving clinical efficacy and safety. This article retrieves relevant research literature published domestically and internationally regarding the regulation of the PI3K/Akt/mTOR signaling pathway by TCM in the treatment of CRC and conducts detailed classification and summary. The active components of TCM include glycosides， flavonoids， alkaloids， terpenoids， polyphenols， and naphthoquinones. The volatile oils and extracts of TCM include Angelicae Sinensis Radix volatile oil， Astragali Radix polysaccharides， Caryophylli Flos extract， Forsythiae Fructus extract， Curcumae Longae Rhizoma extract， and Celastrus orbiculatus extract. The compound formulas of TCM include Banxia Xiexin decoction， Jianpi Qingre Huoxue formula， and Chanling Plaster. Through summary and analysis， it is discovered that the abovementioned TCM can produce effects such as blocking the cell cycle， inducing autophagy and apoptosis， inhibiting angiogenesis， suppressing proliferation and migration， and reversing chemotherapy resistance and radiotherapy resistance by inhibiting the PI3K/Akt/mTOR pathway in CRC cells. TCM holds promise in the research and application of targeting the PI3K/Akt/mTOR signaling pathway for CRC treatment. The summary and conclusion of this article aim to provide references for subsequent research and the development of new drugs.

Objective:To analyze the diagnostic value of inflammatory markers, clinical characteristics of patients with different prognoses, and variations in antimicrobial susceptibility testing for Klebsiella pneumoniae bloodstream infection. Methods:This study involved 166 patients with positive blood cultures for Klebsiella pneumoniae from January 2018 to May 2023 as the Klebsiella pneumoniae-positive group, and 100 patients with negative blood culture results as the negative group. The diagnostic value of inflammatory markers for Klebsiella pneumoniae bloodstream infection was evaluated through receiver operating characteristic (ROC) curve. The differences in C-reactive protein (CRP) and procalcitonin (PCT) levels between Klebsiella pneumoniae bloodstream infections and non- Klebsiella pneumoniae bloodstream infections were analyzed. According to the prognoses, 166 patients with Klebsiella pneumoniae bloodstream infection were divided into two groups: favorable outcome group (105 cases) and adverse outcome group (61 cases). Clinical features, infection sites, empirical use of antibiotics, and antimicrobial susceptibility were compared between the patients with different outcomes. Results:The percentage of neutrophils ( Z=-3.645, P<0.001), CRP level ( Z=-6.809, P<0.001), and PCT level ( Z=-8.214, P<0.001) were significantly higher in the Klebsiella pneumoniae-positive group than in the negative group. The area under the ROC curve (AUC) values for CRP and PCT in diagnosing Klebsiella pneumoniae bloodstream infection were 0.755 and 0.849, respectively. There were variations in CRP ( H=20.902, P<0.001) and PCT ( H=33.521, P<0.001) levels among patients with bloodstream infection caused by Klebsiella pneumoniae, other common negative bacilli, common positive cocci, or Candida. The body temperature, albumin level, hemoglobin level, and length of hospital stay in the adverse outcome group were lower than those in the favorable outcome group ( P<0.05). Besides, the incidence of invasive operation, organ failure, shock, and rescue were also lower in the adverse outcome group ( P<0.05). In the adverse outcome group, co-infections mainly involved respiratory infections, accounting for 60.7% (37/61). Respiratory infections (49.5%, 52/105) were also the predominant co-infections in the favorable outcome group, followed by hepatobiliary infections (34.3%, 36/105). The pathogenic bacteria cultured from different infection sites were mainly Klebsiella pneumoniae. In the favorable outcome group, fluoroquinolones were the most commonly used medications for empirical therapy, with a usage rate of 76.2% (80/105), followed by β-lactamase inhibitor complex preparations (68.6%, 72/105), the usage rate of which were significantly higher than those in the adverse outcome group ( P<0.05). Carbapenems were the preferred drugs for the adverse outcome group, with a usage rate of up to 62.3% (38/61), which was significantly higher than that in the favorable outcome group ( P<0.05). The adverse outcome group showed high resistance rates to ciprofloxacin (40.98%, 25/61) and levofloxacin (37.7%, 23/61), while the resistance rates were 22.86% (24/105) and 32.38% (34/105) in the favorable outcome group. The resistance rates to other drugs were low and there was no significant difference between the two groups ( P>0.05). Conclusions:PCT and CRP have certain value in diagnosing bloodstream infections caused by Klebsiella pneumoniae, and have certain reference significance for differentiating bloodstream infections caused by Gram-negative bacteria, Gram-positive bacteria, and Candida species. The source of bloodstream infection in patients with adverse outcome may be the respiratory system, while in patients with favorable outcome, the main sources of bloodstream infection may be the respiratory and hepatobiliary systems. Antimicrobial susceptibility testing reveals the highest resistance rate to fluoroquinolones. Given their frequent use in empirical therapy, this may lead to treatment failure. Notably, carbapenems are more commonly administered as empirical antibiotics in the adverse outcome group.

Colorectal cancer （CRC） is a prevalent malignant tumor of the digestive tract， with a high incidence and high mortality. The majority of patients are diagnosed at the middle or advanced stage， which severely influences and threatens their physical health. Current treatment modalities such as surgery， radiotherapy， and chemotherapy often encounter challenges including metastasis， recurrence， and drug resistance. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway serves as a classical regulator that regulates physiological processes such as cell cycle， autophagy， apoptosis， and proliferation. Overexpression of this pathway is observed in various tumors. In the context of CRC， the activation of this pathway can facilitate the proliferation， invasion， and migration， inhibit the autophagy and apoptosis， promote the epithelial-mesenchymal transition of CRC cells， enhance angiogenesis within the tumor， and contribute to chemotherapy resistance and radiation resistance in CRC. Traditional Chinese medicine （TCM） treatment can exert an anti-CRC effect by inhibiting this pathway， thereby improving clinical efficacy and safety. This article retrieves relevant research literature published domestically and internationally regarding the regulation of the PI3K/Akt/mTOR signaling pathway by TCM in the treatment of CRC and conducts detailed classification and summary. The active components of TCM include glycosides， flavonoids， alkaloids， terpenoids， polyphenols， and naphthoquinones. The volatile oils and extracts of TCM include Angelicae Sinensis Radix volatile oil， Astragali Radix polysaccharides， Caryophylli Flos extract， Forsythiae Fructus extract， Curcumae Longae Rhizoma extract， and Celastrus orbiculatus extract. The compound formulas of TCM include Banxia Xiexin decoction， Jianpi Qingre Huoxue formula， and Chanling Plaster. Through summary and analysis， it is discovered that the abovementioned TCM can produce effects such as blocking the cell cycle， inducing autophagy and apoptosis， inhibiting angiogenesis， suppressing proliferation and migration， and reversing chemotherapy resistance and radiotherapy resistance by inhibiting the PI3K/Akt/mTOR pathway in CRC cells. TCM holds promise in the research and application of targeting the PI3K/Akt/mTOR signaling pathway for CRC treatment. The summary and conclusion of this article aim to provide references for subsequent research and the development of new drugs.