ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Objective: To investigate the precise detection methods for weak partial D type 15 and evaluate their implications for blood transfusion safety, along with the development of corresponding strategies. Methods: A combination of serological methods, including the microplate method, indirect antiglobulin tube method, and microcolumn gel card method, was employed to identify RhD-negative and RhD variant samples. RhD-negative samples were screened for the presence of RHD genes using whole-blood direct PCR amplification. Subsequently, RhD variant samples and RhD-negative samples containing RHD genes underwent full-coding-region sequencing of the RHD gene to confirm their genotypes. The genotyping results were further correlated with the serological test findings for comprehensive analysis. Results: Among 615 549 first-time healthy blood donors, 3 401 samples with an RhD-negative phenotype and 156 samples with RhD variant were identified. Of the 3 401 RhD-negative samples, 1 054 were found to harbor RHD genes. Gene sequencing analysis of the 156 RhD variants and the 1 054 serological negative samples revealed that 89 samples contained the RHD 15 (c. 845G>A) allele. Conclusion: The integration of serological testing methods and genotyping technologies for the precise determination of RhD blood type plays a critical role in ensuring the safety and compatibility of blood transfusions.

BACKGROUND:In the offspring of obese mothers,some metabolic genes are"silent"under certain environmental influences.These"silent"genes may be"awakened"under the acquired environment and then cause metabolic regulation disorders. OBJECTIVE:In the case of offspring with different diets,to explore the metabolic genetic effects of long-term high-fat and exercise intervention in female mice. METHODS:Seventy 3-week-old female C57BL/6 mice were divided into high-fat diet(HFD)and high-at exercise groups(high-fat diet+exercise,HFD-Ex),and they gave birth naturally after 16 weeks of intervention.After 4-week lactation,16 male offspring mice from each group were randomly selected.Totally 32 offspring mice were randomly divided into 4 subgroups and given high-fat diet or standard chow diet for 6 weeks:HFD-HFD,HFD-Ex-HFD,HFD-standard chow diet,and HFD-Ex-standard chow diet.The offspring mice were subjected to glucose tolerance test and insulin tolerance test in the 10th week,followed by body composition analysis and sacrifice.Western blot was used to determine the level of p-Akt in the liver.Immunofluorescence of the hypothalamic arcuate nucleus was used to analyze the expression of neuropeptide Y and pro-opiomelanocortion. RESULTS AND CONCLUSION:Under the high-fat diet,compared with the HFD group,the offspring of the HFD-Ex group had significantly improvements in glucose metabolism,body mass,and body composition(P＜0.05).Under the standard chow diet,compared with the HFD group,the expression of neuropeptide Y in the hypothalamic arcuate nucleus of the HFD-Ex group was significantly decreased(P＜0.05),and the expression of pro-opiomelanocortion was significantly up-regulated(P＜0.05).In the case of insulin(-),the expression of phosphorylated Akt(Ser473)protein in the liver showed no significant difference between the two groups,but in the case of insulin(+),there was a significant difference between the two groups(P＜0.05).In the high-fat diet mode,the metabolic protection effect of the maternal long-term exercise may gradually weaken with the prolongation of the offspring's high-fat exposure;in the standard chow diet mode,the maternal long-term exercise can improve the central regulation of energy metabolism and insulin sensitivity of the male offspring.

Targeted delivery of antibody bound to antigen is a precise drug delivery mode. It is regarded as one of the ideal targeted drug delivery modes due to its high specificity and affinity, which opens up a new way to successfully solve the problem of poor selectivity of chemotherapy drugs in antitumor therapy. Currently, the research on antibody drug conjugates(ADCs) that bind monoclonal antibodies to target antigens has become a research hotspot of molecular targeted therapy. This paper reviews the mechanism of action, targeting strategies and progress in the targeted delivery of ADCs, in order to provide reference for the clinical development of new ADCs.

OBJECTIVE To prepare patchouli oil enteric-coated dropping pills, evaluate its colon-targeted release behaviors and therapeutic potency against rat ulcerative colitis(UC). METHODS The single factor combined with response surface optimization method was used to screen matrix types and optimize preparation process parameters. Formula and thickness of Eudragit coating was selected based on dissolution tendency toward simulated intestinal fluids. Finally, colon targeting release behavior and the therapeutic effect of the preparation were assessed on the rat UC model induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS). RESULTS The optimal prescription of patchouli oil dropping pills was patchouli oil∶PEG6000∶PEG8000 ratio of 1∶1∶1; and the optimal condition for preparing patchouli oil pills was keeping nozzle temperature at 9 ℃, and dropping pills at the speed of 33 drops·min−1, with dropping distance set at 6 cm; the optimal ratio of Eudragit L100∶Eudragit S100 was 3∶7 for preferential release in simulate intestinal fluid over simulated gastric fluid. Compared with free patchouli oil, patchouli oil enteric-coated dropping pills significantly alleviated the pathological symptoms such as weight loss, hematochezia and colon shortening in rats; the expression of pro-inflammatory cytokines IL-6, IL-1β, and IL-23 in serum was significantly down-regulated and the expression of anti-inflammatory cytokines IL-10 and TGF-β1 was significantly up-regulated. The mRNA expression of Mucin-1 and Mucin-2 in colon tissue was significantly up-regulated and the mRNA expression of inflammatory cytokines IL-6, IL-1β, and TNF-α was significantly down-regulated. CONCLUSION The patchouli oil enteric-coated dropping pills have colon-targeted release ability and improve the anti-inflammatory effect of drugs.

Myocardial fibrosis （MF） is a prevalent pathological process in a spectrum of cardiac conditions， including myocardial infarction， hypertensive heart disease， and dilated cardiomyopathy. It is marked by an overabundance of extracellular matrix deposition， diminished myocardial compliance， and impaired cardiac function， which can lead to arrhythmias and sudden cardiac death. The current therapeutic approach primarily aims to suppress the progression of fibrosis， yet the therapeutic outcomes are poor. The pathogenesis of MF involves multiple signaling pathways， including the transforming growth factor-beta （TGF-β）/Smads signaling pathway， nuclear factor-kappa B （NF-κB） signaling pathway， phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， and mitogen-activated protein kinase （MAPK） signaling pathway. Traditional Chinese medicine （TCM） boasts a rich history in the treatment of cardiovascular diseases， offering distinctive benefits such as minimal side effects and high safety， and it has demonstrated promising therapeutic effects in the treatment of MF. In recent years， research has turned its attention to the application of TCM in modulating the signaling pathways associated with MF. It has been demonstrated that TCM can modulate the MF-related signaling pathways to exert anti-inflammatory effects， regulate cellular autophagy， cell proliferation， and apoptosis， reduce myocardial oxidative stress and damage， and inhibit the activation of fibroblasts and collagen synthesis， thereby exhibiting the potential to mitigate or even reverse the progression of MF. Experimental research and clinical observations indicate that TCM formulas such as Yixin Futing decoction， Luhong prescription， Zhilong Huoxue Tongyu capsules， and Kangjian Yixin prescription can effectively ameliorate MF and enhance cardiac function through the multi-component regulation of multiple cellular pathways. Specific TCM constituents， including isoliquiritigenin and astragaloside， have been shown to inhibit the expression of TGF-β₁， thereby disrupting the Smad signaling pathway. Compounds like glycyrrhizic acid and allicin can suppress the NF-κB signaling pathway and curtail collagen synthesis in myocardial cells， and forsythoside can activate the PI3K/Akt signaling pathway， contributing to its anti-fibrotic effects.

ObjectiveTo investigate the trends and significant determinants of delayed HIV diagnosis （DHD） among newly reported HIV/AIDS cases in Xuhui District， Shanghai between 2018 and 2022. MethodsIn the newly reported HIV/AIDS cases， patients died within one year without accident， HIV/AIDS cases with CD₄ cell count <200 cells·μL^-1， and AIDS cases with a CD₄ cell count between 200 to 499 cells·μL^-1 were defined as delayed diagnosis. Univariate and multivariate logistic analysis were employed to explore the influencing factors of DHD. ResultsAmong the 862 newly reported HIV/AIDS cases， The DHD rate was 39.79% without statistically significant difference by year（χ²=4.508， P=0.342）. Patients with CD₄ cell count <200 cells·μL^-1 contributed the largest proportion of DHD. During 2018‒2022， the DHD rate declined among HIV/AIDS patients who were younger than 35 years old or 45‒65 years old， never married， original diagnosis from tertiary specialized hospitals. Patients who were 65 years or older， married or divorced， with heterosexual transmitted HIV/AIDS， and original diagnosis from other types of testing and tertiary metropolitan hospital， had sustainably higher DHD rates. The number of HIV screening and diagnosed from voluntary counseling and testing （VCT） decreased during the COVID-19 epidemic， while the DHD rate increased sharply. Multivariate logistic regression analysis suggested the DHD rates were higher among older age， other types of testing（OR=3.805， 95%CI： 2.260‒6.406）and pre-operative testing（OR=2.411， 95%CI： 1.424‒4.081）. Patients who received CD₄ test in 15 days had a higher DHD rate compared to the cases received CD₄ test exceeding 90 days （OR=0.336， 95%CI： 0.216‒0.522）. ConclusionThere is no significant decrease of delayed HIV diagnosis rate in Xuhui District in recent years， and the number of HIV tests has decreased in 2022. Monitoring of newly reported HIV/AIDS should be conducted continuously. Expansion of HIV antibody screening should be conducted in non-infectious departments and inpatient departments in healthcare institutions， particularly metropolitan hospitals. Assistance should be provided to clinicians and elderly patients for improving their ability to recognize and perceive the risk of HIV/AIDS， in order to enhance early diagnosis and subsequent treatment.

With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.