The lacrimal gland organoids are innovative in vitro cultured tissue model that mimics the lacrimal gland, retaining its original histological and molecular biological properties. This model can more accurately reproduce the physiological environment of the lacrimal gland, including its ductal system and tear film protein secretion. It offers a new platform for studying the physiopathological basis of the lacrimal gland, establishing disease models, conducting regenerative medicine applications, and performing drug screening. Currently, organoids technology is continuously evolving, with ongoing updates to the methods for in vitro culturing of the lacrimal gland. These advancements gradually address challenges related to cultivation complexity, cost, and time, demonstrating a wide range of application potential. In this paper, we summarize the latest progress in lacrimal gland organoids research both domestically and internationally, exploring the development of lacrimal gland organoids, 3D construction technologies, and their potential for clinical applications, in order to provide new insights for clinical research on lacrimal gland-related diseases and to promote broader application of lacrimal gland organoids in drug development and personalized diagnosis and treatment.

The lacrimal gland organoids are innovative in vitro cultured tissue model that mimics the lacrimal gland, retaining its original histological and molecular biological properties. This model can more accurately reproduce the physiological environment of the lacrimal gland, including its ductal system and tear film protein secretion. It offers a new platform for studying the physiopathological basis of the lacrimal gland, establishing disease models, conducting regenerative medicine applications, and performing drug screening. Currently, organoids technology is continuously evolving, with ongoing updates to the methods for in vitro culturing of the lacrimal gland. These advancements gradually address challenges related to cultivation complexity, cost, and time, demonstrating a wide range of application potential. In this paper, we summarize the latest progress in lacrimal gland organoids research both domestically and internationally, exploring the development of lacrimal gland organoids, 3D construction technologies, and their potential for clinical applications, in order to provide new insights for clinical research on lacrimal gland-related diseases and to promote broader application of lacrimal gland organoids in drug development and personalized diagnosis and treatment.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

Based on the implementation of GMP, comprehensive improvement of quality control measures, and consideration of the 3Rs principle for experimental animals, Several years ago, WHO, the European Pharmacopoeia and the FDA gradually abolished the testing for abnormal toxicity of biological products, and the Chinese Pharmacopoeia 2025 Edition(Volume Ⅲ)also revised the testing for abnormal toxicity of biological products. In order to help users of the Chinese Pharmacopoeia(Volume Ⅲ) better understand and implement this pharmacopoeia, this article provides a detailed review of the changes in regulatory concepts for abnormal toxicity test in various countries and the process of gradually phasing out abnormal toxicity test, as well as the actual situation of China’s pharmaceutical industry. It also interprets the ideas and considerations for revising the Chinese Pharmacopoeia 2025 Edition(Volume Ⅲ) on abnormal toxicity test for biological products.

Objective:To investigate the impact of the interval period between biopsy and MR examination on tumor detection and extraprostatic extension (EPE) assessment for prostate cancer (PCa) using multi-parametric MRI (mpMRI).Methods:The study was cross-sectional and retrospectively included 130 patients with PCa who underwent RP and preoperative systematic biopsies followed by mpMRI between January 2021 and December 2022 in the First Medical Center of Chinese PLA General Hospital. Patients were divided into 3 groups according to interval following biopsy (group A,<3 weeks, 31 cases; group B, 3-6 weeks, 67 cases; group C,>6 weeks, 32 cases). The percentages of hemorrhage volume in the total prostate were drawn on T 1WI and calculated. The junior, senior and expert radiologists independently localized the index lesions and calculated the accuracy for tumor detection, in addition to assessing the probabilities of EPE according to EPE grade. The correlation between the hemorrhage extent and interval was analyzed using the Spearman correlation coefficient. The accuracy for tumor detection was compared using χ2 test among groups. The diagnostic performance of the radiologists for EPE prediction was assessed using the receiver operating characteristic curve, and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. Results:The percentage of hemorrhage was correlated with the interval between biopsy and MR examination ( r=-0.325, P<0.001). The detection accuracy of junior radiologist was 83.9% (26/31), 76.1% (51/67), and 78.1% (25/32) in group A, B and C, respectively; no differences were observed in the detection accuracy among three groups ( χ2=0.76, P=0.685). The detection accuracy of senior radiologist was 83.9% (26/31), 80.6% (54/67), and 71.9% (23/32) in 3 groups with no differences ( χ2=1.53, P=0.464). The detection accuracy of expert radiologist was 80.6% (25/31), 77.6% (52/67), and 93.8% (30/32) with no differences ( χ2=3.95, P=0.139). The AUC (95% CI) for predicting EPE were 0.830 (0.652-0.940), 0.704 (0.580-0.809), 0.800 (0.621-0.920) in the group A, B and C for junior radiologist; 0.876 (0.708-0.966), 0.768 (0.659-0.863), 0.896 (0.736-0.975) for senior radiologist; and 0.866 (0.695-0.961), 0.813 (0.699-0.895), 0.852 (0.682-0.952) for expert radiologist, respectively. No differences were observed among the subgroups in each radiologist ( P>0.05). Conclusion:The interval period does not significantly affect the detection accuracy and EPE assessment of PCa using mpMRI. There is probably no necessity for prolonged intervals following systematic biopsy to preserve the clarity of MRI interpretation for PCa.

BACKGROUND:With the rapid development of minimally invasive spinal surgery and enhanced recovery after surgery,endoscopic intervertebral fusion techniques have gradually emerged and been widely used in clinical practice in recent years. OBJECTIVE:To analyze the early clinical efficacy of uniaxial spinal endoscopic intervertebral fusion combined with posterior percutaneous pedicle screw fixation in the treatment of lumbar degenerative diseases. METHODS:135 patients with lumbar degenerative diseases treated by uniaxial spinal endoscopic intervertebral fusion combined with posterior percutaneous pedicle screw fixation in the Suining Central Hospital from October 2020 to December 2021 were enrolled in this study.There were 59 males and 76 females,aged 47-79 years.The lower limb and lumbar pain was evaluated by visual analog scale and lumbar function was assessed by Oswestry disability index before the operation,1 week,1,and 6 months after the operation,and at the end of follow-up.The overall pain recovery of patients was evaluated by the scoring criteria for low back pain surgery of Spine Group of Chinese Orthopedic Association and the lumbar physiological curvature and intervertebral fusion were evaluated on lumbar lateral X-ray preoperatively and at the end of follow-up. RESULTS AND CONCLUSION:(1)The 135 patients were followed up for(17.8±3.0)months after surgery.There was 1 case of endplate injury,1 case of cerebrospinal fluid leakage,1 case of nerve root injury,1 case of intervertebral cage subsidence and displacement,1 case of chronic infection,and 1 case of pedicle screw rupture.The complication rate was 5.2%.(2)The lumbar visual analog scale score and Oswestry disability index significantly decreased in the waist and lower limbs at various time points postoperatively compared with those preoperatively in 135 patients(P<0.05).The scoring criteria for low back pain surgery of the Spine Group of the Chinese Orthopedic Association were significantly better at the last follow-up than that preoperatively in 135 patients(P<0.05).(3)At the last follow-up,there was no significant difference in physiological curvature of lumbar vertebra as compared with that preoperatively in 135 patients(P>0.05),with a fusion rate of 95.8%.(4)It is concluded that uniaxial spinal endoscopic intervertebral fusion combined with posterior percutaneous pedicle screw fixation in the treatment of lumbar degenerative diseases has shown satisfactory early clinical results and is a highly safe minimally invasive spinal surgery mode.

This article summarized the clinical experience of MEI Guoqiang in treating lung cancer of phlegm-heat obstructed in the lung syndrome with modified Xiaoxianxiong Decoction （小陷胸汤）. It is believed that the key pathogenesis of lung cancer with phlegm-heat obstructed in the lung syndrome is the phlegm-heat toxin accumulation. According to the different pathogenic effects of qi stagnation， blood stasis， pathogenic toxin， phlegm-damp， qi deficiency， yin deficiency in the occurrence and development of the disease， it is advocated to clear heat and resolve phlegm， and additionally the methods of diffusing the lung and relieving cough， resolving toxins and dissipating masses， rectifying qi and activating blood， dispelling dampness， supplementing and boosting qi and yin are used if necessary. Multiple methods are used together and flexibly matched. In clinical practice， Xiaoxian-xiong Decoction with the function of clearing heat and relieving phlegm is recommended as the basic formula for further modification. For patients with mild lung symptoms， modified Xiaoxianxiong Decoction is commonly used， while for those with obvious symptoms， self-made Maxing Xianxiong Decoction（麻杏陷胸汤） in modifications is suggested. For patients with Shaoyang （少阳） diseases， modified Chaihu Xianxiong Decoction （柴胡陷胸汤） is often used.

Purpose To explore the diagnostic value of prostate imaging report and data system 2.1(PI-RADS v2.1)combined with prostate-specific antigen density(PSAD)for clinically significant prostate cancer(csPCa)in prostate-specific antigen(PSA)gray area(4-10 ng/ml)based on two-center data.Materials and Methods The clinical and imaging data of patients with PSA gray zone prostate disease who underwent multi-parametric magnetic resonance imaging and all pathological data in the First Medical Center(center 1)and the Sixth Medical Center(center 2)of the Chinese PLA General Hospital from January 2017 to May 2022 were retrospectively selected and analyzed.The patients from center 1 were used as the training group(220 cases),and the patients from center 2 were used as the test group(50 cases).Logistic regression was used to determine the independent predictors of csPCa in the training group,and the diagnostic efficacy of multi-parameter combination for csPCa was analyzed,which was further verified in the test group.Results There were significant differences in prostate volume,PSAD and PI-RADS v2.1 scores between the csPCa and non-csPCa groups in the training group(Z=-6.468,6.589,75.676,all P＜0.001).Logistic regression analysis showed that PI-RADS v2.1 score and PSAD were the independent risk factors for csPCa(both P＜0.001).The area under the curve of the Logistic regression model composed of PI-RADS v2.1 and PSAD for predicting csPCa in the PSA gray zone was 0.860(95％CI 0.808-0.903)in the training group and 0.906(95％CI 0.790-0.970)in the test group,respectively.The area under the curve of Logistic regression model was significantly higher than that of PI-RADS v2.1 and PSAD,respectively,with statistically significant difference(both P＜0.05).When the PI-RADS v2.1 score was low or moderate risk and PSAD＜0.15 ng/ml2,csPCa in the training group and the test group was with low detection rate.Conclusion PI-RADS v2.1 score and PSAD may be the independent risk factors for predicting csPCa in the PSA gray zone.The combined application of the two methods is better than the single method in the diagnosis of csPCa in the PSA gray zone,with benefits for clinical biopsy decision-making.

Purpose To explore the additional value of apparent diffusion coefficient(ADC)histogram in predicting extraprostatic extension(EPE)of prostate cancer.Materials and Methods Consecutive patients undergoing multi-parameter MRI and subsequent radical prostatectomy from January 2021 to December 2022 were retrospectively included in this study.Two radiologists independently estimated EPE by using national cancer institute grading system for extraprostatic extension(EPE grade system),with disagreement resolved by discussion.Histogram metrics were derived from three-dimensional volumes of interest encompassing the entire lesion on ADC maps using FireVoxel,obtaining mean ADC,1st,5th,10th,25th,50th,75th,90th,95th and 99th ADC values.The ADC histograms between the groups with and without EPE were compared.Multivariable Logistic regression analysis was used to identify the independent predictive factors of EPE,and a combined model was developed.Receiver operator characteristic curve was used to evaluate the diagnostic performance,and the area under the curve was calculated and compared.Results Thirty-four patients(34％)had pathologic confirmed EPE after radical prostatectomy.ADC histogram parameters showed significant differences between patients with and without EPE(P＜0.05).Multivariate Logistic regression analysis revealed 99th ADC(OR=0.609,P=0.008)and EPE grade system(OR=4.158,P＜0.001)were independent predictors of EPE.For predicting EPE,the area under the curve of 99th ADC,EPE grade system and the combined model were 0.756,0.805 and 0.856,respectively.The area under the curve of 99th ADC and the EPE grade system in identifying EPE showed no significant difference.The diagnostic efficacy of combined model was significantly superior to that of 99th ADC or EPE grading system(Z=2.223,2.208,both P＜0.05).Conclusion The ADC histogram parameters demonstrate additional value for preoperative prediction of EPE.Combining the 99th ADC histogram parameter with the EPE grade system may improve the diagnostic efficacy of EPE.