Objective:To establish the method validation of microbial limit tests for hospital paste preparations, including com-pound salicylic acid paste, zinc oxide paste and compound pine tar paste. Methods:According to the microbial limit test described in China pharmacopoeia 2010 edition, the method validation of count of bacteria, fungi and yeasts and tests for specified microorganisms was established. Results:Medium dilution method could be used in bacteria, fungi and yeasts count and specified microorganisms ex-amination for compound salicylic acid paste and zinc oxide paste. For compound pine tar paste, bacteria, fungi and yeasts count and the pseudomonas aeruginosa examination could use medium dilution method, while the staphylococcus aureus examination should employ membrane filtration method. Conclusion:The methods of microbial limit tests for the three hospital paste preparations are established, which can be used to control the quality of hospital preparations effectively.

Neonatal cerebral infaraction(NCI)is the brain injury caused by cerebrovascular disease in neonates within 28 days, which can lead to poor outcome.At present, the etiology of NCI is still unclear, which may involve a variety of risk factors concerning maternal, placental and neonatal issues.The risk of developing NCI increases when risk factors increase.In order to indentify neonates with risk factors and diagnose NCI early, this review summarized the high-risk factors of NCI from three aspects, involving prenatal, intrapartum and postpartum stages.Timely intervention need to be given to improve the prognosis of neonates with NCI.

Objective:To explore whether hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) preconditioning can relieve inflammation, reduce cell apoptosis and alleviate renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly divided into three groups of sham operation (sham), ischemia reperfusion injury (IRI) and IRI+ HIF-PHI ( n=6 each). In IRI+ HIF-PHI group, mice received an intragastric dose of roxadustat (20 mg/kg) every other day one week before. After renal IRI modeling, serum creatinine (SCr) level was monitored and hematoxylin-eosin (HE) staining employed for observing the pathological changes of renal tissue and scoring injury degree. Apoptosis of renal tubular epithelial cells was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mRNA expressions of HIF-1α, TNF-α and IL-1β in renal tissues. Immunofluorescence and immunohistochemistry were employed for detecting the expressions of hypoxia-inducing factor 1α (HIF-1α), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results:As compared with IRI group, SCr level declined markedly in IRI+ HIF-PHI group ( P<0.01), renal tissue injury improved markedly, semi-quantitative score of renal tubule injury dropped ( P<0.01), apoptotic cells decreased ( P<0.01) and the expression levels of TNF-α and IL-1β declined ( P<0.05). Compared with sham group, the mRNA expression of HIF-1α was not significantly elevated in IRI group ( P>0.05). Immunofluorescence showed that the expression of HIF-1α in medulla of renal tissues was up-regulated in IRI group, but not markedly in cortex. While the mRNA expression of HIF-1α was markedly up-regulated after a pretreatment of HIF-PHI ( P<0.05), the expression spiked markedly in renal cortex, but was weaker in medulla than that in IRI group. Conclusions:HIF-PHI can boost the expression level of HIF-1α, reduce the expression of inflammatory factors, relieve the inflammatory response, reduce cell apoptosis, improve renal function and alleviate renal ischemia reperfusion injury.

Objective:Peripheral nerve invasion (PNI) is associated with local recurrence and poor prognosis in patients with advanced gastric cancer. A risk-assessment model based on preoperative indicators for predicting PNI of gastric cancer may help to formulate a more reasonable and accurate individualized diagnosis and treatment plan.Methods:Inclusion criteria: (1) electronic gastroscopy and enhanced CT examination of the upper abdomen were performed before surgery; (2) radical gastric cancer surgery (D2 lymph node dissection, R0 resection) was performed; (3) no distant metastasis was confirmed before and during operation; (4) postoperative pathology showed an advanced gastric cancer (T2-4aN0-3M0), and the clinical data was complete. Those who had other malignant tumors at the same time or in the past, and received neoadjuvant radiochemotherapy or immunotherapy before surgery were excluded. In this retrospective case-control study, 550 patients with advanced gastric cancer who underwent curative gastrectomy between September 2017 and June 2019 were selected from the Affiliated Hospital of Qingdao University for modeling and internal verification, including 262 (47.6%) PNI positive and 288 (52.4%) PNI negative patients. According to the same standard, clinical data of 50 patients with advanced gastric cancer who underwent radical surgery from July to November 2019 in Qingdao Municipal Hospital were selected for external verification of the model. There were no statistically significant differences between the clinical data of internal verification and external verification (all P>0.05). Univariate analysis and multivariate logistic regression analysis were used to determine the independent risk factors for PNI in advanced gastric cancer, and the clinical indicators with statistically significant difference were used to establish a preoperative nomogram model through R software. The Bootstrap method was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index). The calibration curve was used to evaluate the consistency of the predicted results with the actual results. The Hosmer-Lemeshow test was used to examine the goodness of fit of the discriminant model. During external verification, the corresponding C-index index was also calculated. The area under ROC curve (AUC) was used to evaluate the predictive ability of the nomogram in the internal verification and external verification groups. Results:A total of 550 patients were identified in this study, 262 (47.6%) of which had PNI. Multivariate logistic regression analysis revealed that carcinoembryonic antigen level ≥ 5 μg/L (OR=5.870, 95% CI: 3.281-10.502, P<0.001), tumor length ≥5 cm (OR=5.539,95% CI: 3.165-9.694, P<0.001), mixed Lauren classification (OR=2.611, 95%CI: 1.272-5.360, P=0.009), cT3 stage (OR=13.053, 95% CI: 5.612-30.361, P<0.001) and the presence of lymph node metastasis (OR=4.826, 95% CI: 2.729-8.533, P<0.001) were significant independent risk factors of PNI in advanced gastric cancer (all P<0.05). Based on these results, diffused Lauren classification and cT4 stage were included to establish a predictive nomogram model. CEA ≥ 5 μg/L was for 68 points, tumor length ≥ 5 cm was for 67 points, mixed Lauren classification was for 21 points, diffused Lauren classification was for 38 points, cT3 stage was for 75 points, cT4 stage was for 100 points, and lymph node metastasis was for 62 points. Adding the scores of all risk factors was total score, and the probability corresponding to the total score was the probability that the model predicted PNI in advanced gastric cancer before surgery. The internal verification result revealed that the AUC of nomogram was 0.935, which was superior than that of any single variable, such as CEA, Lauren classification, cT stage, tumor length and lymph node metastasis (AUC: 0.731, 0.595, 0.838, 0.757 and 0.802, respectively). The external verification result revealed the AUC of nomogram was 0.828. The C-ndex was 0.931 after internal verification. External verification showed a C-index of 0.828 from the model. The calibration curve showed that the predictive results were good in accordance with the actual results ( P=0.415). Conclusion:A nomogram model constructed by CEA, tumor length, Lauren classification (mixed, diffuse), cT stage, and lymph node metastasis can predict the PNI of advanced gastric cancer before surgery.

Objective:Peripheral nerve invasion (PNI) is associated with local recurrence and poor prognosis in patients with advanced gastric cancer. A risk-assessment model based on preoperative indicators for predicting PNI of gastric cancer may help to formulate a more reasonable and accurate individualized diagnosis and treatment plan.Methods:Inclusion criteria: (1) electronic gastroscopy and enhanced CT examination of the upper abdomen were performed before surgery; (2) radical gastric cancer surgery (D2 lymph node dissection, R0 resection) was performed; (3) no distant metastasis was confirmed before and during operation; (4) postoperative pathology showed an advanced gastric cancer (T2-4aN0-3M0), and the clinical data was complete. Those who had other malignant tumors at the same time or in the past, and received neoadjuvant radiochemotherapy or immunotherapy before surgery were excluded. In this retrospective case-control study, 550 patients with advanced gastric cancer who underwent curative gastrectomy between September 2017 and June 2019 were selected from the Affiliated Hospital of Qingdao University for modeling and internal verification, including 262 (47.6%) PNI positive and 288 (52.4%) PNI negative patients. According to the same standard, clinical data of 50 patients with advanced gastric cancer who underwent radical surgery from July to November 2019 in Qingdao Municipal Hospital were selected for external verification of the model. There were no statistically significant differences between the clinical data of internal verification and external verification (all P>0.05). Univariate analysis and multivariate logistic regression analysis were used to determine the independent risk factors for PNI in advanced gastric cancer, and the clinical indicators with statistically significant difference were used to establish a preoperative nomogram model through R software. The Bootstrap method was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index). The calibration curve was used to evaluate the consistency of the predicted results with the actual results. The Hosmer-Lemeshow test was used to examine the goodness of fit of the discriminant model. During external verification, the corresponding C-index index was also calculated. The area under ROC curve (AUC) was used to evaluate the predictive ability of the nomogram in the internal verification and external verification groups. Results:A total of 550 patients were identified in this study, 262 (47.6%) of which had PNI. Multivariate logistic regression analysis revealed that carcinoembryonic antigen level ≥ 5 μg/L (OR=5.870, 95% CI: 3.281-10.502, P<0.001), tumor length ≥5 cm (OR=5.539,95% CI: 3.165-9.694, P<0.001), mixed Lauren classification (OR=2.611, 95%CI: 1.272-5.360, P=0.009), cT3 stage (OR=13.053, 95% CI: 5.612-30.361, P<0.001) and the presence of lymph node metastasis (OR=4.826, 95% CI: 2.729-8.533, P<0.001) were significant independent risk factors of PNI in advanced gastric cancer (all P<0.05). Based on these results, diffused Lauren classification and cT4 stage were included to establish a predictive nomogram model. CEA ≥ 5 μg/L was for 68 points, tumor length ≥ 5 cm was for 67 points, mixed Lauren classification was for 21 points, diffused Lauren classification was for 38 points, cT3 stage was for 75 points, cT4 stage was for 100 points, and lymph node metastasis was for 62 points. Adding the scores of all risk factors was total score, and the probability corresponding to the total score was the probability that the model predicted PNI in advanced gastric cancer before surgery. The internal verification result revealed that the AUC of nomogram was 0.935, which was superior than that of any single variable, such as CEA, Lauren classification, cT stage, tumor length and lymph node metastasis (AUC: 0.731, 0.595, 0.838, 0.757 and 0.802, respectively). The external verification result revealed the AUC of nomogram was 0.828. The C-ndex was 0.931 after internal verification. External verification showed a C-index of 0.828 from the model. The calibration curve showed that the predictive results were good in accordance with the actual results ( P=0.415). Conclusion:A nomogram model constructed by CEA, tumor length, Lauren classification (mixed, diffuse), cT stage, and lymph node metastasis can predict the PNI of advanced gastric cancer before surgery.

Objective To analyze the causal relationship between serum sex steroid hormone levels and myopia with the Mendelian randomization(MR)methods.Methods Sex hormone genetic tools classified by sex were publicly availa-ble summarized statistical data from the Genome-wide association study(GWAS)of the UK Biobank Consortium on sex hormone-binding globulin(SHBG),total testosterone(TT),bioavailable testosterone(BT),and estradiol(E2).The GWAS summarized statistical data for myopia were obtained from publicly available data published by the FinnGen Consorti-um R10.All data were downloaded from April 18 to April 31,2024 from the corresponding databases and analyzed.All re-sults from the MR study were mainly analyzed by inverse-variance weighting(IVW)method.Results The study showed that a higher serum SHBG level in European increased the risk of myopia development in women(IVW,OR=1.152,95％CI:1.014-1.308,P=0.029);low serum TT level(IVW,OR=0.821,95％CI:0.697-0.967,P=0.018)and serum BT lev-el(IVW,OR=0.820,95％CI:0.691-0.972,P=0.022)increased the risk of myopia development in women.There was no causal relationship between serum SHBG,TT,and BT levels and myopia in men.There was no causal effect between E2 level and myopia in women and men.The stability of our findings was supported by sensitivity analysis.Conclusion In-creased serum SHBG level and decreased serum TT and BT levels are associated with an increased risk of myopia in women,whereas no such association is found in men.There is no causal relationship between E2 and myopia.

OBJECTIVETo perform a prospective,multicenter,open,randomized study to determine a treatment regimen for treatment-naive patients with refractory chronic hepatitis C (RHC) using the predictive value (PV) of early virological response (EVR).

METHODSA total of 438 patients from 18 hospitals were recruited between December 2008 and December 2010 and administered peg-interferon/ribavirin treatment for 12 weeks. Patients who achieved complete EVR (cEVR) were assigned to group A for a 48-week course of treatment, while patients without cEVR were randomly allocated to either group B 1 for a 72-week course of treatment or to group B2 for a 96-week course of treatment. Serum hepatitis C virus RNA levels at baseline,treatment weeks 4, 12 and 24, end of treatment, and post-treatment week 24 were measured and used to evaluate the efficiency of therapy.

RESULTSThe overall sustained virological response (SVR) rate was 85.1%. In all, 91.0% of patients achieved cEVR and were assigned to group A, which had an SVR rate of 90.8%. There was no statistically significant difference in the SVR rates of groups B1 and B2 (29.4% vs. 25.0%, P more than 0.05). The positive PV of rapid virological response (RVR), cEVR and delayed virological response (DVR) for SVR was 93.4%, 90.8% and 77.8% respectively, and the negative PV of RVR, EVR and DVR for SVR was 28.0%, 93.3% and 100% respectively. Overall, 66.9% of the patients experienced adverse events (AEs), but only 1.9% of patients experienced sevcre AEs.

CONCLUSIONThe majority of Chinese RHC treatmentna(i)ve patients (91.0%) can achieve cEVR and a high SVR rate with a low rate of severe AEs using the cEVR guided personal treatment regimen.

Myopia is a significant global health issue,and its exact causes are still not fully understood,leaving a lack of effective and propaqable treatment options.The prevalence of myopia among children and adolescents in China remains high,posing challenges for prevention and control efforts.According to the"theory of imbalance of essence and tendon",an imbalance in the essential elements and tendons can impede the passage of eye essence and blood,resulting in delayed expansion and contraction of the eye meridians and tendons,leading to blurred vision.Modern research indicates that during the development of myopia,there are notable changes in the microstructure,activation range,and signaling of various brain regions,providing a biological basis for the"brain-eye"mechanism.Moreover,abnormal activity in the brain nucleus contributes to alterations in choroid blood flow and the impairment of eye muscle regulation,thereby accelerating the progression of myopia,this phenomenon represents the manifestation of the brain-eye imbalance.Consequently,strategies for myopia prevention and control should prioritize nourishing kidney essence,replenishing brain marrow,promoting liver and blood health,and softening the meridians.These measures aim to optimize the functioning of the brain and eyes,maintain the flexibility of eye tendons,enhance eye regulation,sustain the strength of eye tendons,and delay the advancement of eye axis growth and myopia.By enriching the scientific understanding of the appropriate application of traditional Chinese medicine techniques to prevent and control myopia through the brain,this research provides valuable insights for future explorations in this field.

Diabetic retinopathy(DR)is one of the major complications of diabetes mellitus, characterized by neurodegeneration and microangiopathy. Currently, the treatment of DR is mainly focused on the management of late complications and has not achieved the desired clinical outcome. Evidence suggests that the PI3K/AKT pathway, as one of the important intracellular signaling pathways during the cell cycle, is involved in the whole process of DR pathogenesis. This article focuses on the structural composition, activation and blocking pathways, conduction pathways, regulatory mechanisms and biological functions of the PI3K/AKT signaling pathway to review its role in DR and to explore the potential of targeting the PI3K/AKT pathway for the treatment of DR.

ObjectiveTo observe the effectiveness and safety of the Chinese herbal medicine Mingshi Granules （明视方颗粒） for low myopia in children with heart yang insufficiency. MethodsA multicentre， prospective， double-blind randomised controlled study was conducted， in which 290 children with low myopia from 8 centres were randomly divided into 145 cases in the treatment group and 145 cases in the control group， and the treatment group was given education， dispensing glasses， and Chinese herbal medicine Mingshi Granules， while the control group was given education， dispensing glasses， and granules placebo. Both Mingshi Granules and placebo granules were taken orally， 1 bag each time， twice daily， 4 weeks of oral intake and 2 weeks of rest as 1 course of treatment， a total of 4 courses of treatment （24 weeks）. Equivalent spherical lenses， best naked-eye distance visual acuity， ocular axis， corneal curvature K1， adjustment amplitude， traditional Chinese medicine （TCM） symptom scores， calculate the amount of progression of equivalent spherical lenses， were observed at the 12th and the 24th week of treatment， at the 36th week and 48th week of follow-up， resectively， the control rate of myopia progression was evaluated at the 24th week， and safety indexes were observed before treatment. ResultsThe amount of progression of equivalent spherical lenses was lower in the treatment group than in the control group at the 48-week follow-up （P＜0.05）. The control rate of myopia progression at 24 weeks after treatment in the treatment group was higher （57.60%， 72/125） than that in the control group （44.63%， 54/121） （P＜0.05）. The best naked-eye distance visual acuity at 36-week follow-up in the treatment group was higher than that in the control group （P＜0.05）. Equivalent spherical lenses were significantly lower in both groups at all observation time points compared with pre-treatment （P＜0.05）， and were higher in the treatment group than in the control group at the 48-week follow-up （P＜0.05）. The ocular axes of both groups were significantly higher at each observation time point after treatment and at follow-up compared with before treatment （P＜0.05）. The amount of eye axis growth in the treatment group was lower than that in the control group at 24 weeks after treatment and at the 48-week follow-up （P＜0.05）. Corneal curvature K1 was significantly lower in the treatment group at the 24th week of treatment compared to pre-treatment （P＜0.05）. The magnitude of adjustment in the treatment group was significantly higher at the 36-week follow-up and at the 48-week follow-up than before treatment （P＜0.05）. The scores of white/dark complexion， white coating thin pulse， fatigue and total TCM symptom scores of children in both groups at the 12th， 24th， 36th and 48th weeks of follow-up were significantly lower than those before treatment （P＜0.05）； the scores of blurred vision at the 24th and 36th weeks of follow-up were significantly lower than those before treatment （P＜0.05）； and the scores of blurred vision in the treatment group at the 48th week of follow-up were signi-ficantly lower than those before treatment （P＜0.05）. In the treatment group， the score of fatigue was higher than that of the control group at the 36-week follow-up， and the score of blurred vision was lower than that of the control group at the 48-week follow-up （P＜0.05）. No adverse reactions or obvious abnormalities of the safety indexes were observed of the two groups during the treatment. ConclusionChinese herbal medicine Mingshi Granules showed the effect of controlling the progression of low myopia， improving the best naked eye distance visual acuity， slowing down the growth of the eye axis， improving some of the TCM symptoms， with good safety.