To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.

BACKGROUND: Growing evidence suggests that long non-coding RNAs (lncRNAs) exert pivotal roles in fostering chemoresistance across diverse tumors. Nevertheless, the precise involvement of lncRNAs in modulating chemoresistance within the context of gallbladder cancer (GBC) remains obscure. This study aimed to uncover how lncRNAs regulate chemoresistance in gallbladder cancer, offering potential targets to overcome drug resistance. METHODS: To elucidate the relationship between gemcitabine sensitivity and small nucleolar RNA host gene 1 ( SNHG1 ) expression, we utilized publicly available GBC databases, GBC tissues from Renji Hospital collected between January 2017 and December 2019, as well as GBC cell lines. The assessment of SNHG1, miR-23b-3p, and phosphatase and tensin homolog (PTEN) expression was performed using in situ  hybridization, quantitative real-time polymerase chain reaction, and western blotting. The cell counting kit-8 (CCK-8) assay was used to quantify the cell viability. Furthermore, a GBC xenograft model was employed to evaluate the impact of SNHG1 on the therapeutic efficacy of gemcitabine. Receiver operating characteristic (ROC) curve analyses were executed to assess the specificity and sensitivity of SNHG1. RESULTS: Our analyses revealed an inverse correlation between the lncRNA SNHG1 and gemcitabine resistance across genomics of drug sensitivity in cancer (GDSC) and Gene Expression Omnibus (GEO) datasets, GBC cell lines, and patients. Gain-of-function investigations underscored that SNHG1 heightened the gemcitabine sensitivity of GBC cells in both in vitro and in vivo  settings. Mechanistic explorations illuminated that SNHG1 could activate PTEN -a commonly suppressed tumor suppressor gene in cancers-thereby curbing the development of gemcitabine resistance in GBC cells. Notably, microRNA (miRNA) target prediction algorithms unveiled the presence of miR-23b-3p binding sites within SNHG1 and the 3'-untranslated region (UTR) of PTEN . Moreover, SNHG1 acted as a sponge for miR-23b-3p, competitively binding to the 3'-UTR of PTEN , thereby amplifying PTEN expression and heightening the susceptibility of GBC cells to gemcitabine. CONCLUSION The SNHG1/miR-23b-3p/PTEN axis emerges as a pivotal regulator of gemcitabine sensitivity in GBC cells, holding potential as a promising therapeutic target for managing GBC patients.
Humans ; Deoxycytidine/pharmacology* ; PTEN Phosphohydrolase/genetics* ; Gemcitabine ; RNA, Long Noncoding/metabolism* ; MicroRNAs/genetics* ; Gallbladder Neoplasms/genetics* ; Cell Line, Tumor ; Animals ; Mice ; Drug Resistance, Neoplasm/genetics* ; Mice, Nude ; Antimetabolites, Antineoplastic ; Gene Expression Regulation, Neoplastic

Perimenopausal syndrome （MPS）， a common endocrine system disease， is one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in endocrinology， gynecology， and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine， TCM， and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency， with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause， whereas such a therapy has certain risks， necessitating close monitoring of adverse reactions. Moreover， the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes， sweating， sleep disorders， and emotional abnormalities of MPS without causing obvious adverse reactions. However， its efficacy is slower than the hormone replacement therapy， and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First， an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second， high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third， efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

BACKGROUND:Currently,there are few kinds of drugs to treat kidney diseases,and many systemic drugs have some problems,such as serious side effects,rapid degradation in the body circulation and so on.At present,active targeting of nanoparticles has become a hot spot in the field of drug delivery,and the exploration of the pathological mechanism related to active targeting of nanoparticles is becoming more and more abundant. OBJECTIVE:To summarize the active targeting strategies in common renal diseases. METHODS:The first author and the second author searched CNKI,Wanfang,VIP,and PubMed databases using"nanoparticles,active targeting,target,kidney,kidney disease"as English key words and"nanoparticles,nanoparticles,targeting,active targeting,kidney disease,kidney"as Chinese key words.All relevant articles published before July 2,2023 were retrieved,screened,concluded,and summarized.Finally,62 articles were included for the summary. RESULTS AND CONCLUSION:The active targeting effect of nanoparticles has been studied in many common kidney diseases.The mechanism of active targeting is mainly the binding of ligands and receptors,by modifying the ligand on the nanoparticles to specifically target the receptor on the cells in the kidney;in which way active targeting is realized.Under different renal pathological conditions,the pathological changes of specific kidney sites may become the key breakthrough point to achieve active targeting.Although kidney-targeting nanoparticles have shown promise in the treatment of nonneoplastic kidney diseases,but it is still in the experimental phase in animals,and it is still a long way from applying these results to medical work.

Objective:The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored.Methods:The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot.Results:Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5′SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level.Conclusion:The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.

Objective To analyze the current situation of dietary diversity and caregiver self-efficacy for complementary feeding among infants and young children aged 6 to 23 months in rural Nanchong city,Sichuan province,and to explore the relationship between dietary diversity and caregiver self-efficacy.Methods Multi-stage randomized cluster sampling method was used to select infants and young children aged 6 to 23 months and their caregivers in rural areas of Nanchong city,Sichuan province as the subjects.A structured questionnaire was designed to collect the basic information of the subjects,dietary diversity,and caregiver self-efficacy for comple-mentary feeding.Multivariate Logistic regression was adopted to analyze the relationship between the dietary diver-sity and caregiver self-efficacy for complementary feeding of infants and young children.Results A total of 770 pairs of infants and young children and their caregivers were included.The minimum pass rate of dietary diversity was 61.56% (474/770)for all the infants and young children and 45.00% (108/240),69.16% (287/415),and 68.70% (79/115)for the infants and young children aged 6 to 11,12 to 17,and 18 to 23 months,respective-ly.The results of regression analysis showed that the caregiver self-efficacy of complementary feeding was a contributing fac-tor for qualified dietary diversity of infants and young children in the case of other confounders being controlled(OR = 1.42,95% CI=1.17-1.73,P<0.001).Conclusion The dietary diversity for infants and young children in rural Nan-chong city,Sichuan province needs to be improved,and caregivers with higher self-efficacy of complementary feeding are more likely to provide diversified complementary feeding for infants and young children.

ObjectiveTo explore the therapeutic effect and mechanism of Yiqi Huoxue Tongbian prescription on slow transit constipation （STC） in rats. MethodThe rat model of STC was established by gavage of loperamide hydrochloride. Rats were assigned into control， model， mosapride， low-， medium-， and high-dose （3.51， 7.02， and 14.04 g·kg^-1， respectively） Yiqi Huoxue Tongbian prescription groups. The changes of general signs， fecal moisture content， and intestinal propulsion rate were measured after model establishment and drug administration. The colonic mucosal changes were observed by hematoxylin eosin staining. Enzyme-linked immunosorbent assay was employed to determine the content of substance P （SP） and vasoactive intestinal peptide （VIP） in the colon of rats in each group. The gray values of aquaporin （AQP） 3， AQP4， AQP8， and c-Kit in rat colon tissue were measured by immunohistochemistry and Western blot， and the changes of intestinal flora were detected by 16S rRNA high-throughput sequencing. ResultCompared with the model group， 10 days of treatment with Yiqi Huoxue Tongbian prescription increased the fecal moisture content and intestinal propulsion rate （P<0.01）. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups and the mosapride group showed no obvious mucosal inflammation and neat arrangement of goblet cells with a large number in the colon tissue. Moreover， the three groups showed increased SP content （P<0.01） and decreased VIP content （P<0.01） in the serum. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups showed down-regulated protein levels of AQP3， AQP4， and AQP8 （P<0.01） and up-regulated protein level of c-Kit （P<0.01）. The drug administration groups presented slightly increased observed species， Chao1， ACE， and Shannon， Simpson， and PD whole tree. The principal component analysis showed that the control group had a short distance with the high- and medium-dose Yiqi Huoxue Tongbian prescription groups， indicating that high- and medium-dose Yiqi Huoxue Tongbian prescription can recover the intestinal flora to that in the control group. ConclusionYiqi Huoxue Tongbian prescription can alleviate the defecation status of rats with slow transit constipation by down-regulating the expression of AQP3， AQP4， and AQP8 to reduce the absorption of water in the intestine， up-regulating the expression of c-Kit to increase the number and distribution of Cajal interstitial cells， and regulating the balance of flora in the colon tissue.

Objective:To investigate the value of delta radiomics based on longitudinal changes of dynamic contrast enhanced MRI (DCE-MRI) in predicting pathological complete response (pCR) after neoadjuvant therapy (NAT) for breast cancer.Methods:The clinicopathological and imaging data of 117 patients with breast cancer confirmed by surgical pathology from April 2019 to November 2021 at Jiangxi Cancer Hospital were analyzed retrospectively. All patients were female with 23?74 (48±10) years old. The patients were randomly divided into training (81 cases) and test sets (36 cases) at the ratio of 7∶3 according to the number of random seeds in the software. All patients underwent DCE-MRI before and after early NAT (2 courses). The maximum diameter relative regression value of breast tumors before and after early NAT (D%) was calculated and used to construct a conventional imaging model. The delta radiomic features were extracted based on pre-NAT and early-NAT (2 courses) DCE-MRI and selected by redundancy analysis and least absolute shrinkage and selection operator algorithm. A ten-fold cross-validation method was used to construct the delta radiomic model and Radscore was calculated for each patient. All patients were classified into pCR group and non-pCR group according to the surgical pathology after NAT. Significant clinicopathological variables were selected by univariate analysis and stepwise regression method. They were integrated with D% and Radscore to build the combined model and nomogram. The model performance in predicting pCR after NAT in breast cancer was evaluated by the receiver operating characteristic curve and the area under the curve (AUC), and the clinical utility of the models was compared by using clinical decision curves.Results:The combined model had the best diagnostic performance among the three models, with an AUC of 0.90 in the training set and 0.87 in the test set. The Radscore had the highest weight in the nomogram. In the training set, the diagnostic performance of the combined model and delta radiomics model were better than that of the conventional imaging model ( Z=?3.48, P=0.001; Z=2.54, P=0.011). The clinical decision curves showed an overall greater clinical benefit of the combined model compared with the conventional imaging model and delta radiomic model. Conclusions:The addition of significant clinicopathological variables and Radscore of delta radiomic model which represents the longitudinal changes in tumor heterogeneity to the conventional imaging model may improve the predictive ability of pCR. The delta radiomic may serve as a noninvasive biomarker for early prediction of NAT response.

Objective:To study the ultrasonographic characteristics of embryos/fetuses with normal or abnormal central nervous system (CNS) from 7 to 13 +6 weeks of gestation using high resolution two-dimensional ultrasound combined with HD-live silhouette technology and provide a reference for early diagnosis of CNS abnormalities. Methods:Eighty normal embryos/fetuses during 7-13 +6 weeks and 41 fetuses with CNS malformations in early pregnancy during 11-13 +6 weeks were selected to observe the ultrasonographic features of embryos/fetuses with normal or abnormal CNS using transvaginal high resolution two-dimensional ultrasound and HD-live silhouette technology. Descriptive analysis was performed on the results. Results:From seven weeks of gestational age, high resolution two-dimensional ultrasound combined with HD-live silhouette technology can clearly and stereoscopically show the prosencephalon, mesencephalon and rhombencephalon. The rhombencephalon changed the most in the brain development of embryos. At nine weeks of gestation, cleared structures of pons curvature, the fourth ventricle and cisterna magna were observed. The developing cerebellum and the original Blake pouch cyst were seen at 10 weeks of gestation. From 11 to 13 +6 weeks, the most remarkable change was the choroid plexus of the fourth ventricle changed from perpendicular to parallel to the long axis of the neural tube. Of the 41 fetuses with CNS malformation, 16 (39.0%) were exencephaly, 11 (26.8%) were holoprosencephaly, five (12.2%) were encephalocele, four (9.7%) were anencephaly, three (7.3%) were fourth ventricle dilatation, and two (4.9%) were open spina bifida. Conclusions:High resolution two-dimensional ultrasound combined with HD-live silhouette technology can clearly and stereoscopically display the morphological changes in embryonic embryos/fetuses with development of normal CNS at 7-13 +6 weeks, which is helpful to better understand the origin of CNS embryonic abnormalities and provide diagnostic clues for the early detection of CNS abnormalities.