ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

[Objective] In view of the crucial role of indole propionic acid in the treatment of tumor immune checkpoint blockade and further revealing its mechanism, our study intended to design and synthesize 1-[¹⁸F]-fluoroethyl-indole propionic acid (1-[¹⁸F]-IPA), and evaluate it as a tumor PET imaging agent. [Methods] The precursor 1-(2-p-toluenesulfonic acid oxygen ethyl)-methyl indole propionate underwent nucleophilic substitution reaction with ¹⁸F^-. The crude product was separated and purified by high-performance liquid chromatography and the intermediates were collected. Finally, 1-[¹⁸F]-IPA was obtained by hydrolysis. The clarity of the product was measured by visual inspection, the pH value was determined by precision test paper, and the radiochemical purity and stability were determined by high-performance liquid chromatography. In order to determine the biodistribution of 1-[¹⁸F]-IPA in normal mice, ICR mice were intravenously injected with 1-[¹⁸F]-IPA (0.2 mL, 7 MBq), and sacrificed at 5, 15, 25, 45, 75 and 120 min and dissected. Micro-PET imaging was performed and analyzed in BxPC-3 tumor-bearing nude mice. Student t test was used to compare the biodistribution of tissues and organs at different time points. [Results] The total preparation time of 1-[¹⁸F]-IPA was 35-40 min, the radiochemical yield was (45±5)%, and the radiochemical purity was more than 95%. The product solution was clear without particles, and the pH value was 6.5, which had good stability in vitro and in vivo. The results of biodistribution in healthy ICR mice showed that except for the brain, 1-[¹⁸F]-IPA had a certain uptake in all major organs, with the most obvious uptake in the liver, gallbladder and kidneys. The radioactivity in the gallbladder gradually increased with time and reached (39.86±6.56)%ID/g at 120 min, but bone uptake did not change significantly with time. Micro-PET/CT showed that there was radioactive uptake at the tumor 30 min after injection of 1-[¹⁸F]-IPA in Dutch BxPC-3 nude mice, but it was not obvious. At this time, SUVmax was about 55.18±14.62. Consistent with the results of biodistribution, the brain uptake was low at each time point. [Conclusion] In summary, 1-[¹⁸F]-IPA with short preparation time and high yield is expected to be a tool to probe tryptophan indole metabolism pathway and further reveal tumor immune resistance.

Lipids,including fats(triglycerides)and lipoids(phospholipids and sterols),not only serve as an energy source for the body but also play a pivotal role throughout the reproductive process,particularly in the establishment and maintenance of early pregnancy.This encompasses the regulate of early embryonic development and uterine tolerance,and the facilitation of embryo implantation.Given the diversity of lipids,this review focuses on extensively studied lipid mediators such as polyunsaturated fatty acids,endocannabinoids,prostaglandins,lysophosphatidic acid,sphingolipids and steroid hormones.It systematically elaborates on the regulatory effects of fatty acid,phospholipid,and cholesterol metabolism on the formation of endometrial receptivity and embryo implantation,as well as the potential underlying mechanisms.The review aims to provide new insights and feasible intervention approaches for predicting and improving the outcomes of natural pregnancy and/or assisted reproductive technology.

Objective To investigate the effects of exercise and complex environment on lipopolysaccharide(LPS)-induced dopaminergic neuron death in the substantia nigra of midbrain.Methods C57BL/6 mice were divided into control group,LPS group,LPS+swimming group and LPS+complex environment group,with 7 mice in each group.The mice in the LPS group were injected with LPS into the brain to establish an inflammatory model of Parkinson's disease and lived in cages for 2 weeks.Mice in LPS+swimming group were forced to swim for 15 minutes every day for 2 weeks after modeling.The mice in the LPS+complex environment group were placed in a complex environment for 2 weeks after modeling.The control group mice were not treated.After 14 days of modeling,behavioral experiments such as footprint,open field and rotating rod were performed on each group of mice to detect the autonomous exercise ability,exercise balance ability and depression level of mice.The expressions of tyrosine hydroxylase(TH)in substantia nigra was detected by immunohistochemical staining and Western blotting.The expressions of brain-derived neurotrophic factor(BDNF),Caspase-3,interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the substantia nigra of the midbrain were detected by Western blotting.The transcription levels of IL-1β,IL-6 and TNF-α in substantia nigra were detected by RT-PCR.Results Compared with the control group,the exercise ability and balance ability of mice in LPS group,LPS+swimming group and LPS+complex environment group decreased,the depression level increased(P＜0.001),the number of TH positive neurons and BDNF protein decreased significantly(P＜0.001),and the contents of Caspase-3,IL-1β,IL-6 and TNF-α increased significantly(P＜0.001).Compared with the LPS group,the exercise ability and balance ability of the mice in the LPS+swimming group and the LPS+complex environment group were restored,the depression level decreased significantly(P＜0.01),the survival number of TH positive neurons and the content of BDNF increased significantly(P＜0.01),Caspase-3,IL-1β,IL-6 and TNF-α reduced significantly(P＜0.01),and the phenomenon in the LPS+complex environment group was more significant.Conclusion Exercise and complex environment can inhibit LPS-induced central nervous system inflammation in mice,thereby reducing damage to midbrain substantia nigra neurons,and the inhibitory effect of LPS+complex environment group is more significant.

Objective To compare the clinical efficacy and pregnancy outcomes of CO2 laser and loop electrosurgical excision procedure(LEEP)surgery in the treatment of cervical high-grade squamous intraepithelial lesion(HSIL)in women of childbearing age.Methods Patients with cervical HSIL of appropriate reproductive age(20-34 years old)who underwent satisfied colposcope,subsequently treated with laser or LEEP between Jan 2019 and Dec 2021 in Obstetrics and Gynecology Hospital,Fudan University were collected.All the patients were interpreted as transformation zone(TZ)type 1/2,and colposcopy biopsy diagnosed as cervical high-grade squamous intraepithelial lesion(HSIL)and received laser or LEEP according to the physician's advice and the patient's wishes.The effectiveness of the two surgeries was evaluated,and postoperative cytology,HPV result,and colposcopic pathology were compared.We monitored the surgical pregnancy rate,pregnancy complications,and pregnancy results after the surgery.Results A total of 566 cases,including 233 laser cases and 333 LEEP cases,were enrolled.There was no significant difference between the two groups in terms of preoperative cytology,HPV distribution,or the length of cervical canal.After 6 months of surgery,91.5%of patients who underwent laser therapy and 86.9%of those who underwent LEEP had normal cytology.The histology cure rate was 91.5%and the HPV conversion rate was 74.6%in both groups.The results of cytology,HPV,and colposcopic pathology had no significant difference between the two groups.The length of postoperative cervical canal was significantly longer in laser group than that in LEEP group[(29.09±3.15)mm vs.(27.05±3.84)mm,P<0.001].There was no statistically significant difference in postoperative pregnancy rate and pregnancy outcome between the two groups.Conclusion Laser ablation and LEEP produce comparable effects pregnancy outcomes in cervical HSIL patients with TZ types 1 and 2,while LEEP has pathologic feedback,so its misdiagnosis of invasive cancer reduce.

Aim To explore the potential mechanism of action of Codonopsis Poria in the treatment of alco-holic liver disease(ALD).Methods TCMSP and Swiss Target Prediction were used to obtain the active ingredients and targets of Codonopsis Poria;OMMI,DisGeNET and GeneCards databases were used to obtain the targets of ALD;STRING database was used to construct the PPI network;and Bioconductor soft-ware was used to analyze the enrichment of GO and KEGG pathways.Cytoscape 3.7.1 software was used to construct the drug-component-target-disease network of Codonopsis Poria for ALD treatment,and key targets were screened for molecular docking;the effects of Codonopsis Poria on ALD rats were verified by experi-ments.Results The removal of duplicate targets ob-tained 36 chemical components and 529 potential ac-tion targets.GO enrichment analysis:2 245 biological processes,74 cellular components,125 molecular functions.KEGG enrichment analysis:159 signaling pathways,mainly involving PI3K-Akt,MAPK,AGE-RAGE signaling pathways.Molecular docking showed that AKT1,MMP9 and other targets may be the key targets of Codonopsis Poria in the treatment of ALD.Experiments showed that Codonopsis Poria could im-prove the inflammation level of hepatocytes in ALD rats and reduce the levels of TC,TG,AST,ALT and GGT in ALD rats,PCR assay concluded that Codonopsis Po-ria could reduce the expression of PI3 K and AKT,and electron microscopy results showed that Codonopsis Po-ria could affect the autophagy of cells.Conclusions It is initially revealed that Codonopsis Poria may atten-uate inflammatory cell infiltration by affecting the ex-pression of AKT,TNF and MAPK,and it is hypothe-sized that Codonopsis Poria may affect autophagy through the PI3K-Akt signaling pathway,thus treating ALD,which is initially verified by PCR assay to pro-vide a basis for in-depth explanation of the molecular mechanism of Codonopsis Poria medicinal pairs in the treatment of ALD.

ObjectiveTo explore the effects of Baihu Jia Renshen Tang （BHRS） on the related molecules on the phosphatidylinositol-3-kinase/protein kinase B（PI3K/Akt）signaling pathway in the liver of MKR diabetic model mice. MethodThirty 6-week-old MKR mice were selected and fed on a high-fat diet for four weeks，followed by intraperitoneal injection of streptozotocin（STZ）for the diabetes model establishment. The model was properly induced in the case of the fasting blood glucose （FBG） of ≥11.1 mmol·L^-1. After modeling，the mice were randomly divided into a model group，a BHRS group （12.09 g·kg^-1·d^-1），and a metformin group （0.065 g·kg^-1·d^-1），with 10 mice in each group. Ten FVB mice were assigned to the control group. The mice in the groups with drug intervention were continuously administered correspondingly for 28 days. After administration，the mice were sacrificed，followed by the oral glucose tolerance test （OGTT） and FBG detection. Serum very low-density lipoprotein（VLDL）content was determined by semi-quantitative enzyme-linked immunosorbent assay （ELISA）. Four indexes related to blood lipid were determined by the biochemistry analyzer. Liver tissues were subjected to pathological examination by hematoxylin-eosin（HE）staining. Western blot was used to detect the protein expression of PI3K，Akt，phosphorylated（p）-PI3K，p-Akt，forkhead box protein O1 （FoxO1），insulin receptor（InsR），and insulin receptor substrate-2（IRS-2） in liver tissues of mice. Real-time polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression of PI3K，Akt，FoxO1，InsR，and IRS-2 in liver tissues of mice. ResultCompared with the control group，the model group showed poor general conditions，abnormal glucose tolerance （P<0.05），increased FBG （P<0.01），abnormal blood lipid metabolism，increased serum total cholesterol （TC），triglyceride（TG），low-density lipoprotein cholesterol（LDL-C），and VLDL （P<0.05），decreased level of high-density lipoprotein cholesterol（HDL-C）（P<0.05），fatty degeneration and obvious pathological changes of liver cells，reduced protein expression of PI3K，Akt，p-PI3K/PI3K，p-Akt/Akt，IRS-2，and InsR in liver tissues（P<0.05），increased protein expression of FoxO1（P<0.05），decreased mRNA expression of PI3K，Akt，IRS-2，and InsR in liver tissues （P<0.05），and increased FoxO1 mRNA expression（P<0.05）. Compared with the model group，the BHRS group showed improved general conditions and glucose and lipid metabolism （P<0.05），improved pathological state of liver cells，increased protein expression of PI3K，Akt，p-PI3K/PI3K，p-Akt/Akt，IRS-2，and InsR in liver tissues（P<0.05），decreased protein expression of FoxO1（P<0.05），increased mRNA expression of PI3K，Akt，IRS-2，and InsR in liver tissues （P<0.05），and reduced FoxO1 mRNA expression（P<0.05）. ConclusionBHRS can effectively reduce blood glucose，regulate blood lipid metabolism，and improve the pathological state of the liver in MKR diabetic mice，and its mechanism of action may be related to the regulation of the activity of molecules on the PI3K/Akt signaling pathway.

By integrating plant metabonomics and target quantitative analysis methods, this study systematically analyzed the differences of chemical constituents in Scutellaria baicalensis leaves from different producing areas in Shanxi, so as to provide theoretical basis for rational and effective utilization of Scutellaria baicalensis leaves. Based on the idea of plant metabonomics, the liquid quality of 53 batches of Scutellaria baicalensis leaves from 8 different producing areas in Shanxi was analyzed by UPLC-QTOF-MS, and the collected data were imported into SIMCA 14.1 software for multivariate statistical analysis to screen the different chemical constituents among different habitats in Shanxi. Meanwhile, a method for simultaneous determination of 7 flavonoids and 3 organic acids in Scutellaria baicalensis leaves was optimized and established to quantitatively analyze the differences of chemical components in Scutellaria baicalensis leaves from different producing areas in Shanxi. The results of plant metabonomics showed that there were differences in the chemical composition of Scutellaria baicalensis leaves in northern Shanxi (Datong, Xinzhou), Jinzhong (Yangquan, Luliang) and southern Shanxi (Changzhi, Yuncheng, Jincheng, Linfen): there were 14 significant differences in chemical composition between northern Shanxi and Jinzhong; there were 18 significant differences in chemical constituents between southern Shanxi and central Shanxi. There were 15 significant differences in chemical constituents between northern Shanxi and southern Shanxi. Among them, scutellarin and isocarthamidin-7-O-glucuronide were the common differences among the three regions, and the content of scutellarin was the highest in southern Shanxi and the lowest in northern Shanxi. The content of isocarthamidin-7-O-glucuronide was the highest in Jinzhong area and the lowest in northern Shanxi area. Quantitative analysis further confirmed that the average contents of apigenin, naringenin and citric acid were the highest in northern Shanxi, scutellarin, caffeic acid, apigenin-7-O-glucuronide, malic acid and wogonoside were the highest in southern Shanxi, and wogonoside and baicalin were the highest in central Shanxi. This study is of great significance to the quality control of Scutellaria baicalensis leaf resources, and provides theoretical basis for rational and effective utilization of Scutellaria baicalensis leaf resources.

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.
Humans ; Urinary Bladder Neoplasms/diagnosis* ; Carcinoma, Transitional Cell/pathology* ; Reproducibility of Results ; DNA Copy Number Variations ; Kidney Neoplasms ; Ureteral Neoplasms ; Sensitivity and Specificity

Objective: To compare the efficacies between open surgery and axillary non-inflatable endoscopic surgery in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 343 patients with unilateral PTC treated by traditional open surgery (201 cases) and transaxillary non-inflating endoscopic surgery (142 cases) from May 2019 to December 2021 in the Head and Neck Surgery of Sichuan Cancer Hospital. Among them, 97 were males and 246 were females, aged 20-69 years. 1∶1 propensity score matching (PSM) was performed on the enrolled patients, and the basic characteristics, perioperative clinical outcomes, postoperative complications, postoperative quality of life (Thyroid Cancer-Specific Quality of Life), aesthetic satisfaction and other aspects of the two groups were compared after successful matching. SPSS 26.0 software was used for statistical analysis. Results: A total of 190 patients were enrolled after PSM, with 95 cases in open group and 95 cases in endoscopic group. Intraoperative blood losses for endoscopic and open groups were [20 (20) ml vs. 20 (10) ml, M (IQR), Z=-2.22], postoperative drainage volumes [170 (70)ml vs. 101 (55)ml, Z=-7.91], operative time [135 (35)min vs. 95 (35)min, Z=-7.34], hospitalization cost [(28 188.7±2 765.1)yuan vs. (25 643.5±2 610.7)yuan, x¯±s, t=0.73], postoperative hospitalization time [(3.1±0.9)days vs. (2.6±0.9)days, t=-3.24], and drainage tube placement time [(2.5±0.8) days vs. (2.0±1.0)days, t=-4.16], with statistically significant differrences (all P<0.05). There was no significant difference in surgical complications (P>0.05). There were significant diffferences between two groups in the postoperative quality of life scores in neuromuscular, psychological, scar and cold sensation (all P<0.05), while there were no statistically significant differences in other quality of life scores (all P>0.05). In terms of aesthetic satisfaction 6 months after surgery, the endoscopic group was better than the open group, with statistically significant difference (χ²=41.47, P<0.05). Conclusion: Endoscopic thyroidectomy by a gasless unilateral axillary approach is a safe and reliable surgical method, which has remarkable cosmetic effect and can improve the postoperative quality of life of patients compared with the traditional thyroidectomy.
Male ; Female ; Humans ; Thyroid Cancer, Papillary/surgery* ; Retrospective Studies ; Quality of Life ; Thyroid Neoplasms/pathology* ; Endoscopy ; Thyroidectomy/methods*