ObjectiveTo observe the effect of Liuwei Dihuangwan on behavioral impairments in the rat model of autism spectrum disorder （ASD） and explore the mechanism of action. MethodsTwelve SD pregnant rats were intraperitoneally injected with valproic acid （VPA） （10 rats） or normal saline （2 rats）， and male offspring were selected to establish the model of ASD and the control rats. Rats were randomly assigned into model， low-dose （0.75 g·kg^-1） and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan， vitamin D （positive drug， 3.7×10^-5 g·kg^-1）， and blank groups. Each group was administrated with the corresponding concentration of drugs or the same volume of normal saline by gavage for 2 weeks. After the intervention， the three-chamber social test was conducted to evaluate social interaction and social preference. The open field test was carried out to observe spontaneous behavior and anxiety state. Hematoxylin-eosin staining （HE） was used to observe the pathological changes of the prefrontal tissue. Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in prefrontal neurons. Immunofluorescence was used to detect the expression of ionized calcium-binding adapter molecule-1 （Iba-1） in the prefrontal tissue. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was employed to assess the expression differences of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated Unc-51-like autophagy-activating kinase 1 （p-ULK1）， Unc-51-like autophagy-activating kinase 1 （ULK1）， and FUN14 domain-containing protein 1 （FUNDC1）. ResultsCompared with the blank group， the model group spent less time sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.01） and showed reductions in the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.01）. In addition， the model group showed extensive apoptosis of neurons， with shrunken nuclei and red-stained cytoplasm， and extensive necrosis of neurons in the prefrontal tissue， mitochondrial swelling， decreased matrix density， disrupted cristae， and autophagic lysosomes in neurons， increases in the rate of Iba-1 positive cells in the prefrontal area （P<0.01） and the levels of TNF-α and IL-6 （P<0.01）， and down-regulation in the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. Compared with the model group， low-dose and high-dose Liuwei Dihuangwan and the vitamin D prolonged the time spent sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.05， P<0.01）， increased the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.05， P<0.01）， restored the morphology of neurons in the prefrontal tissue， decreased the number of apoptotic cells， alleviated the swelling of mitochondria in neurons， increased the matrix density， mitigated the fragmentation and disorder of cristae， and increased the number of autophagosomes. Moreover， the drugs decreased the rate of Iba-1 positive cells in the prefrontal area （P<0.01）， lowered the levels of TNF-α and IL-6 （P<0.01）， and up-regulated the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. ConclusionLiuwei Dihuangwan ameliorate autism-like behaviors and reduce neuronal apoptosis and neuroinflammatory damage in the rat model of ASD by promoting mitophagy mediated by the AMPK/ULK1/FUNDC1 pathway.

Oxidative stress is a pivotal factor in the onset and progression of diabetic kidney disease （DKD）， and it plays an essential role in the prevention and treatment of DKD. The "Gaozhuo" pathogenesis posits that DKD is characterized by the invasion of Gaozhuo and damage to the kidney collaterals， with the underlying cause being the insufficiency of spleen Qi and the internal formation of Gaozhuo， which provides valuable guidance on oxidative stress. The insufficiency of spleen Qi and the internal formation of Gaozhuo represent a dynamic， evolving process. Gaozhuo invades the kidney collaterals， impairs kidney Qi， and progressively leads to the congealing and stagnation of Gaozhuo and blood， ultimately resulting in the failure of both the spleen and kidneys. The damage caused by Gaozhuo to the kidney collaterals and kidney Qi is analogous to the organ and functional damage of the kidneys induced by excessive reactive oxygen species and oxidative stress. Damage to the kidney collaterals means organic injuries to the glomeruli， renal tubules， and renal interstitium， and the depletion of kidney Qi refers to damage to glomerular filtration and renal tubular reabsorption. The congealing and stagnation of Gaozhuo and blood in the kidney collaterals is similar to oxidative stress-induced thickening of the glomerular basement membrane and fibrosis. The interaction between spleen and kidney Qi deficiency and the congealing and stagnation of Gaozhuo and blood creates a vicious cycle that exacerbates the condition， ultimately evolving into the failure of both the spleen and kidneys. The failure of the spleen and kidneys is analogous to renal failure， and its extreme manifestation is end-stage renal disease and uremia. The treatment of oxidative stress in DKD with traditional Chinese medicine （TCM） is based on the principles of strengthening the spleen and tonifying the kidneys， and dispelling turbidity and removing blood stasis. According to the syndrome type， it is recommended to use methods such as strengthening the spleen and tonifying Qi while dispelling dampness and removing turbidity， strengthening the spleen and tonifying the kidneys while dispelling dampness and removing turbidity， strengthening the spleen and tonifying the kidneys while dispelling turbidity and removing blood stasis， or consolidating the spleen and kidneys while clearing away turbidity and blood stasis.

OBJECTIVE To provide a reference for anticoagulation therapy， adverse drug reaction monitoring， and individualized medication adjustment in complex cases， such as those with thrombocytopenia following bioprosthetic heart valve replacement. METHODS Clinical pharmacists participated in the pharmaceutical care of a patient with thrombocytopenia following bioprosthetic heart valve replacement. For cardiac insufficiency， the pharmacists recommended maintaining oral bisoprolol， sacubitril/valsartan， spironolactone， furosemide， and potassium chloride， with levosimendan added to enhance myocardial contractility， while monitoring blood pressure， heart rate and serum potassium levels. For thrombocytopenia， based on literature- based risk assessment， the pharmacists advised administering recombinant human interleukin-11 （rhIL-11）， platelet transfusion， and employing anticoagulation therapy with nadroparin calcium bridging to warfarin， with warfarin dosage adjusted according to the international normalized ratio （INR）. For rapid ventricular rate atrial fibrillation， amiodarone and digoxin were recommended. For acute liver injury， suspected to be induced by amiodarone and rhIL-11， the pharmacists suggested discontinuing the relevant drugs and treating with ademetionine 1，4-butanedisulfonate combined with polyene phosphatidylcholine for liver protection treatment. The patient received anticoagulation medication education emphasizing strict INR monitoring and close observation for bleeding or thrombotic events. RESULTS The clinicians adopted these recommendations. Following the intervention， the patient’s liver function showed significant improvement， with alanine aminotransferase decreasing to 70 U/L and aspartate aminotransferase to 42 U/L. The ventricular rate stabilized at 70-100 beats per minute， cardiac function remained stable， the INR was maintained within the target range of 1.80-2.50， and the patient was ultimately discharged with improved condition. CONCLUSIONS Through balancing anticoagulation and bleeding risks， the clinical pharmacists applied pharmaceutical expertise to assist in developing personalized anticoagulation regimens， conducted adverse drug reaction monitoring and evaluation， and optimized medication strategies， thereby effectively ensuring patient safety and therapeutic efficacy.

ObjectiveTo observe the clinical efficacy of tonifying kidney and replenishing essence on asthenozoospermia patients with the syndrome of kidney essence deficiency and the effects of this method on the adenosine 5′-monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin complex 1 （mTORC1） signaling pathway. MethodsSeventy-two eligible asthenozoospermia patients with the syndrome of kidney essence deficiency treated in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from February 2023 to January 2024 were selected and randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group received oral administration of Guilu Tianjing capsules， while the control group received oral administration of L-carnitine oral solution. The treatment course lasted for 4 weeks in both groups. The observed indicators included sperm progressive motility rate （PR）， total sperm motility （PR+NP）， percentage of normal mitochondrial membrane potential （MMP）， and traditional Chinese medicine （TCM） symptom scores before and after treatment in both groups. A three-month follow-up was instituted to record the conception status of the patients’ spouses. Additionally， eight patients were randomly selected from the eligible patients in the observation group， and four healthy males with normal semen routine examination results were included as the control group for the determination of protein expression. Western blotting was conducted to assess the expression of AMPK， phosphorylated （p）-AMPK， regulatory-associated protein of mTOR （RAPTOR） and p-RAPTOR， and PTEN-induced putative kinase 1 （PINK1） in sperms from the observation group before and after treatment， as well as in the sperms of the control group. ResultsThe pregnancy rate of spouses in the observation group was 9.09% （3/33）， which was higher than that （3.33%， 1/30） in the control group. The total response rate was 84.8% （28/33） in the observation group and 66.7% （20/30） in the control group， with no statistically significant difference. After treatment， both groups were improved considering PR， PR+NP， MMP， and TCM symptom scores （P<0.01）. Moreover， the observation group exhibited more pronounced decreases in TCM symptom scores than the control group （P<0.05）， while the changes in PR， PR+NP， and MMP showed no statistical significance between groups. Compared with the control group， the asthenozoospermia group exhibited upregulations in phosphorylation levels of AMPK and RAPTOR and protein level of PINK （P<0.01）. The administration of Guilu Tianjing Capsules led to downregulations in the phosphorylation levels of AMPK and RAPTOR and protein level of PINK1 （P<0.01）. However， the protein levels of AMPK and RAPTOR demonstrated no significant difference between before and after treatment. During the study period， neither group of patients exhibited any notable adverse reactions. ConclusionGuilu Tianjing capsules can enhance the sperm motility and percentage of normal mitochondrial membrane potential in asthenozoospermia patients with the syndrome of kidney essence deficiency by downregulating the AMPK/mTORC1 signaling pathway， lowering the protein level of PINK1， and inhibiting excessive activation of mitophagy.

ObjectiveTo observe the clinical efficacy of tonifying kidney and replenishing essence on asthenozoospermia patients with the syndrome of kidney essence deficiency and the effects of this method on the adenosine 5′-monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin complex 1 （mTORC1） signaling pathway. MethodsSeventy-two eligible asthenozoospermia patients with the syndrome of kidney essence deficiency treated in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from February 2023 to January 2024 were selected and randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group received oral administration of Guilu Tianjing capsules， while the control group received oral administration of L-carnitine oral solution. The treatment course lasted for 4 weeks in both groups. The observed indicators included sperm progressive motility rate （PR）， total sperm motility （PR+NP）， percentage of normal mitochondrial membrane potential （MMP）， and traditional Chinese medicine （TCM） symptom scores before and after treatment in both groups. A three-month follow-up was instituted to record the conception status of the patients’ spouses. Additionally， eight patients were randomly selected from the eligible patients in the observation group， and four healthy males with normal semen routine examination results were included as the control group for the determination of protein expression. Western blotting was conducted to assess the expression of AMPK， phosphorylated （p）-AMPK， regulatory-associated protein of mTOR （RAPTOR） and p-RAPTOR， and PTEN-induced putative kinase 1 （PINK1） in sperms from the observation group before and after treatment， as well as in the sperms of the control group. ResultsThe pregnancy rate of spouses in the observation group was 9.09% （3/33）， which was higher than that （3.33%， 1/30） in the control group. The total response rate was 84.8% （28/33） in the observation group and 66.7% （20/30） in the control group， with no statistically significant difference. After treatment， both groups were improved considering PR， PR+NP， MMP， and TCM symptom scores （P<0.01）. Moreover， the observation group exhibited more pronounced decreases in TCM symptom scores than the control group （P<0.05）， while the changes in PR， PR+NP， and MMP showed no statistical significance between groups. Compared with the control group， the asthenozoospermia group exhibited upregulations in phosphorylation levels of AMPK and RAPTOR and protein level of PINK （P<0.01）. The administration of Guilu Tianjing Capsules led to downregulations in the phosphorylation levels of AMPK and RAPTOR and protein level of PINK1 （P<0.01）. However， the protein levels of AMPK and RAPTOR demonstrated no significant difference between before and after treatment. During the study period， neither group of patients exhibited any notable adverse reactions. ConclusionGuilu Tianjing capsules can enhance the sperm motility and percentage of normal mitochondrial membrane potential in asthenozoospermia patients with the syndrome of kidney essence deficiency by downregulating the AMPK/mTORC1 signaling pathway， lowering the protein level of PINK1， and inhibiting excessive activation of mitophagy.

[Objective] To analyse the distribution of antigen phenotypes in the Rh, MNS and Kidd blood group systems of Han and Tujia blood donors in Chongqing, and to provide data support for the establishment of an expanded blood group antigen phenotype database and the development of expanded blood group coordinated transfusion in blood donors. [Methods] The antigens of Rh, MNS and Kidd blood group systems in Han and Tujia blood donors in Chongqing were detected by test-tube method, and the Hardy-Weinborg anastomosis of the three blood group systems was calculated. Pearson's chi-square test and Fisher's exact probability method were used to compare the differences in phenotypic distribution frequencies among different regions and ethnic groups. [Results] Han and Tujia blood donors accounted for the highest proportion of CCee in the antigenic phenotype of the Rh blood group system, followed by CcEe, and then Ccee and ccEE. Tujia blood donors accounted for 52.02% of CCee, which was higher than that of Han blood donors (47.24%), while Han blood donors accounted for 32.20% of CcEe, which was higher than that of Tujia blood donors (28.94%). In the antigenic phenotype of the MNS blood group system, the blood donors of Han nationality and Tujia were MN>MM>NN,. The antigen phenotype distribution frequency of the Kidd blood group system was highest for Jk(a+b+) among both Han and Tujia blood donors, and the blood donors of Han nationality were Jk(a+b+)>Jk(a+b+), while those of Tujia were Jk(a-b+)>Jk(a+b-). The antigens of the three blood groups of Han and Tujia blood donors were consistent with the Hardy-Weinberg balance(P>0.05). There was no statistically significant difference in the frequency of antigen phenotypes of the three blood group systems between Han and Tujia blood donors(P>0.05). There were statistically significant differences in the phenotypic distribution frequency of Rh antigens between Chongqing and Xi'an, Zhejiang, Shantou, Foshan, Nanning and Yangzhou(P<0.05), but not with Guang'an and Shenzhen(P>0.05). There were statistically significant differences in the phenotypic distribution frequency of Rh antigens between Han, Tujia, Zang, Mongolian, Korean and Hani ethnic groups in Chongqing(P<0.05). There were statistically significant differences in the phenotypic distribution frequency of MNS antigens between Han blood donors in Chongqing and Urumqi, Hainan and Yuncheng, but not with Xi'an and Wenzhou. There was a statistically significant difference in the phenotypic distribution frequency of MNS antigen between Tujia blood donors in Chongqing and Urumqi and Hainan(P<0.05), but there was no significant difference in the phenotypic distribution frequency of MNS antigen between Tujia blood donors in Chongqing, Urumqi and Hainan(P>0.05). There was a statistically significant difference in the phenotypic distribution frequency of Kidd antigens between blood donors in Chongqing and Harbin(P<0.05), but not in Huizhou, Wenzhou and Yichang(P>0.05). [Conclusion] The population in Chongqing has multi-ethnic characteristics, and the antigenic phenotypes of Rh, MNS and Kidd blood group systems exhibit diversity and regional differences. Establishing an expanded blood bank can provide more options for precision blood transfusion.

Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.

BACKGROUND:Traditional Chinese medicine has rich experience and unique advantages in the empirical treatment of phlegm-heat and Fu-organs excess syndrome of ischemic stroke.In order to further explore the therapeutic targets and mechanisms of traditional Chinese medicine for this disease,it is crucial to establish a stable and reliable animal model of phlegm-heat and Fu-organs excess syndrome combined with empirical symptoms of ischemic stroke. OBJECTIVE:To explore the establishment method and evaluation system of the rat model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome. METHODS:Sixty male Sprague-Dawley rats were randomly divided into four groups:blank control group(n=12),ischemic stroke group(n=18),disease+syndrome group(n=18),phlegm-heat and Fu-organ excess syndrome group(n=12),all of which were given high-fat diet for 25 days.On the 26th day,the rats in the blank control group and ischemic stroke group were intragastrically given normal saline and high fat diet,while those in the other two groups were intragastrically given autologous feces suspension and high fat diet for 3 continuous days.After gavage,ischemic stroke models were established using the suture method in the ischemic stroke group and disease+syndrome group.The changes in diet,water intake,body mass,body temperature,fecal traits,nasal secretions,sputum in the throat,and tongue image were recorded.Neurological deficits,tongue image,blood lipid levels,morphological changes of brain tissue and carotid artery,and the serum levels of motilin and somatostatin were detected. RESULTS AND CONCLUSION:Compared with the control group,the rats in the disease+syndrome group had shortness of breath,listlessness,irritability,bradykinesia,a large number of secretions around the nose,audible and heavy sputum in the throat,decreased diet and water intake,increased body mass,body temperature,and slingual vein score,decreased fecal pellet count,Bristol score and fecal moisture content,increased serum total cholesterol,triglyceride,low-density lipoprotein and somatostatin levels,decreased motilin level,increased neurological deficit score,significant pathological changes of the carotid artery,and significant morphological changes of the brain tissue.The ischemic stroke group only showed pathological changes of ischemic brain tissue,without the characteristics of phlegm-heat and Fu-organ excess syndrome.The phlegm-heat and Fu-organ excess syndrome group could present with the typical characteristics of traditional Chinese medicine syndromes,without the pathological changes of brain tissue with ischemic stroke.To conclude,the compound modeling method of high-fat induction combined with suture method and autologous feces gavage can establish an animal model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome.

Twelve compounds were isolated from the rice fermentation extracts of Penicillium expansum GY618 by silica column chromatography, Sephadex gel column chromatography, ODS column chromatography and semi preparative HPLC methods. They were determined as 11-hydroxyl-penicitrinone F (1), penicitrinone F (2), betulin (3), erythrodiol (4), ergosterol (5), ergost-5α,8α-epidioxy-6,22-dien-3β-ol (6), (5α,8α-epidioxy-(22E,24R)-ergosta-6,9(11),22-trien-3β-ol) (7), 5α,8α-epidioxy-(22E,24R)-23-methylergosta-6,22-dien-3β-ol (8), 5α,8α-epidioxy- 23,24(R)-dimethylcholesta-6,9(11),22-trien-3β-ol (9), dankasterone A (10), (17R)-4-hydroxy-17-methylincisterol (11) and ergosta-4,6,8(14),22-tetraen-3-one (12), through mass spectrometer, nuclear magnetic resonance (NMR) and comparison with the literature. Compound 1 was a new compound and compounds 2-4, 6-12 were isolated from Penicillium expansum fungus for the first time. The tyrosinase inhibitory activity experiment showed that compounds 1, 3 and 12 showed certain inhibitory activity against tyrosinase with IC₅₀ values of (75 ± 9), (69 ± 8) and (64 ± 2) μmol·L^-1, respectively. The IC₅₀ of other compounds were all greater than 100 μmol·L^-1, while IC₅₀ of the positive control kojic acid was (46 ± 4) μmol·L^-1.