This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

OBJECTIVE: To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele（VC）with male infertility. METHODS: A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis. The patients were divided into the microscopic group (180 cases) and laparoscopic group (127 cases) according to the surgery method. The pre- and postoperative clinical data of these two groups were analyzed, including the degree of dilatation and reflux time of internal spermatic vein，hemodynamic parameters of testicular capsular artery，proportion of progressive motility spermatozoa (PR), concentration of spermatozoa, proportion of normal morphology sperm，the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively. RESULTS: All the surgeries for the 307 patients in this study were successful. There was no significant difference in operation time, hospitalization time and management expenses between the microscopic group and the laparoscopic group (P>0.05). Compared to the patients in laparoscopic group, the patients in the microscopic group received a better improvement in venous diameter, reflux time of spermatic veins and hemodynamic parameters of testicular capsular artery (P<0.05). Moreover, the semen analysis showed that the PR, spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group (P<0.05). During the 2-year follow-up period, the conception rate of spouses in the microscopic group was 67.2%, while only 47.2% in the laparoscopic group, in which the difference was statistically significant (P<0.05). Besides, the time-to-pregnancy ( TTP ) within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group（P<0.05). Meanwhile, the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group (P<0.05). It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group (P<0.05). Severe complication such as testicular atrophy, bleeding and infection did not appear in both of two groups. However, the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group (P<0.05). CONCLUSION Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility. But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters, semen quality, pregnancy outcome and postoperative complications, which is worthy of further clinical applications.
Humans ; Male ; Varicocele/complications* ; Laparoscopy ; Infertility, Male/etiology* ; Retrospective Studies ; Adult ; Microsurgery ; Treatment Outcome ; Pregnancy ; Female

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective:To analyze the clinical characteristics of different types of anomalous origin of the coronary artery.Methods:A case-series study was conducted.Based on the clinical data of children diagnosed with anomalous origin of the coronary artery at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from January 2013 to January 2023, the diseases of different types of anomalous origin of the coronary artery were summarized.Results:A total of 177 children with anomalous origin of the coronary artery were treated.Among them, 122 children developed the anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), including 54 males and 68 females, with a median age of 1.2 years; 6 children developed the anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA), including 3 males and 3 females, with a median age of 4.3 years; 9 children developed the anomalous left coronary artery from the right coronary sinus (ALCA), including 6 males and 3 females, with a median age of 9.5 years; 40 children developed the anomalous right coronary artery from the left coronary sinus (ARCA), including 24 males and 16 females, with a median age of 7.7 years.Most children diagnosed with ALCAPA had onset within 1 year of age, with chronic heart failure as the main manifestation, and young children were often accompanied by severe mitral regurgitation.A total of 111 children underwent surgery, and 11 children died.Six children with ARCAPA had no obvious clinical symptoms and were treated by operation according to the principle of double coronary circulation after diagnosis.Nine children with ALCA started with syncope, chest pain or abdominal pain after exercise.Eight of the children underwent surgical treatment, including 1 who received a heart transplant.Of the 40 children with ARCA, 23 children had clinical manifestations, with chest tightness, syncope, and chest pain after exercise as chief complaints; 16 children were tested positive for treadmill exercise before surgery; and a total of 13 children received surgical treatment.Conclusions:Different types of anomalous origin of the coronary artery vary in severity.The clinical manifestations of the anomalous origin of the left coronary artery are generally serious, and most of such patients have the risk of cardiac insufficiency or sudden death.Once diagnosed, surgical treatment should be performed timely.The clinical manifestations of the anomalous origin of the right coronary artery are relatively mild, and only a few may have serious consequences, which are usually treated according to the principle of individualization or double coronary circulation.

ObjectiveTo investigate the levels of serum antibodies against novel coronavirus （SARS-CoV-2） in healthcare workers after one month of natural infection， to explore the influencing factors and their correlations with the levels of antibodies， and to provide reference for strengthening the protection of healthcare workers and preventive intervention in Pudong New Area in Shanghai. MethodsVenous blood samples were collected from 1 102 medical staff in Pudong hospitals one month after infection. The serum levels of new coronavirus specific antibodies IgM， IgG and neutralizing antibodies were detected by chemiluminescent immunoassay. The information of gender， age， position， infection severity， vaccination， basic diseases and use of immunosuppressants were obtained by questionnaire to explore the influencing factors and their correlation with the antibody level. ResultsOne month after natural infection， 99.00% （1 091/1 102） of the subjects were found to be positive for IgG antibody against the new coronavirus， 17.79% （196/1 102） of the subjects were IgM antibody positive， and 99.00% （1 091/1 102） of the samples were positive for the neutralizing antibody. The level of antibody might be influenced by the severity of infection， the time of the last dose of vaccination， and the long-term use of immunosuppressants. The more severe the disease， the stronger the neutralizing antibody response. The antibody level in the people who received the final dose of vaccine within 6 months was higher than that of the people who received the vaccine 6 months ago， and the difference was statistically significant. The antibody levels were low in the subjects who received long-term immunosuppressants. ConclusionThe specific IgM， IgG and neutralizing antibody were found， one month after infection， in the medical workers in Pudong New Area， Shanghai， and the antibody titers were high， which had a good protective effect. The antibody level of the people who were vaccinated within 6 months was higher， it is recommended that people who receive the last vacination more than 6 months should be re-vaccinated with the booster vaccine， to improve the autoimmunity against the novel coronavirus.

Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through in vitro and in vivo experiments. In the mouse ALI model, the effects of RA on liver function and inflammatory indexes were studied, the pathological changes of liver were observed by HE, the effect of RA on reactive oxygen species in liver was detected by fluorescence method, and the level of F4/80 in liver tissue was detected by immunohistochemical method. The levels of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate specific proteinase-1 (CASPASE-1) in liver tissue were measured by Western blot. All animal welfare and experimental procedures follow the rules of the Animal Ethics Committee of Southwest Minzu University. In vitro, human hepatoma cell line HepG2 was used to establish the model of oxidative damage induced by H₂O₂. The cell viability was detected by CCK-8 method. The level of interleukin-1β (IL-1β) in the supernatant was detected by enzyme linked immunosorbent assay (ELISA), the activity of lactatede hydrogenase (LDH) was detected by LDH kit, and the level of ROS was detected by fluorescence probe DCFH-DA labeling. The mRNA expression of Txnip, Nlrp3, Caspase 1, Il1β was detected by real-time fluorescence quantitative PCR (qPCR), and the protein levels of nuclear factor erythroid-2 related factor 2 (NRF2), TXNIP, NLRP3 and CASPASE-1 were measured by Western blot. The results showed that compared with the model group, the degree of liver swelling, tissue injury, liver function index in RA group were significantly lower than those in model group. And RA significantly attenuated the increases of ROS in liver tissue. The expression levels of TXNIP, NLRP3 and CASPASE-1 in liver tissue were significantly lower than those in model group. Additionally, RA inhibited the expressions of F4/80 and IL-1β. In vitro experiment, compared with model group, RA effectively inhibited the secretion of IL-1β and LDH. The level of ROS also decreased significantly. RA inhibited the mRNA expressions of Txnip, Caspase 1, Il1β. Furthermore, RA significantly increased the expression level of NRF2 protein in nucleus, and decreased the expression level of TXNIP and NLRP3 protein. Specifically, with the addition of ML385, the effect of RA on NRF2, TXNIP, NLRP3, CASPASE-1 protein expression was reversed. Collectively, these findings suggested that RA may inhibit the production of ROS by promoting NRF2 nuclear transfer, and then reduce the activation of NLRP3 inflammatory bodies by TXNIP, reduce cell death and inflammatory response to prevent the liver injury.

The adulteration and counterfeiting of herbal ingredients in medicinal and food homology (MFH) have a serious impact on the quality of herbal materials, thereby endangering human health. Compared to pharmaceutical drugs, health products derived from traditional Chinese medicine (TCM) are more easily accessible and closely integrated into consumers' daily life. However, the authentication of the authenticity of TCM ingredients in MFH has not received sufficient attention. The lack of clear standards emphasizes the necessity of conducting systematic research in this area. This study utilized DNA barcoding technology, combining ITS2, psbA-trnH, matK as universal barcode sequences, and DX, HH, JYH as specific barcode sequences, to identify the authenticity of commercial medicinal and food homology scented herbal teas. The aim was to investigate the authenticity of scented herbal tea products circulating in the market. The research results revealed that among 180 scented herbal tea samples, DNA barcodes were successfully obtained from 164 samples, while the remaining samples either lacked the target components or suffered severe DNA degradation, resulting in failed amplification. Combined with morphological identification studies, it was found that out of the 180 samples, 141 were authentic, accounting for 78.33% of the total samples, while 31 samples showed adulteration and 8 samples lacked the target components, accounting for 21.67% of the total samples. Additionally, water testing revealed that 5 samples of Carthamus tinctorius herbal tea exhibited the phenomenon of weight adulteration. This study exposed the presence of adulteration and weight adulteration in scented herbal tea products, highlighting the need for regulatory authorities to expedite the establishment of quality standards in scented herbal tea industry. These findings provide valuable insights for the rapid development of the scented herbal tea industry.

Objective To investigate the biocompatibility of new gadolinium-doped hydroxyapatite(Gd-HA)composite scaffolds and to explore their feasibility as cell culture materials and bone tissue engineering scaffolds.Methods The Gd-HA composite scaffolds were chemically synthesized and placed under the electron microscope for observation.The experiment was divided into three groups,the HA group,the Gd-HA group,and the control group.Rabbit adipose-derived mesenchymal stem cells(ADSCs)were isolated,cultured and characterized,and the Gd-HA composite scaffold extract was added to the ADSCs in vitro culture system.Cell survival and cytotoxicity were assessed by live-dead cell staining,cell proliferation ability within the scaffolds was assessed by CCK-8 assay,and the scaffolds were assessed by alizarin red staining for cell osteogenic differentiation.The toxic reactions of the scaffold materials were observed by skin irritation test,systemic acute toxicity test and muscle tissue and liver and kidney pathology at the site of intramuscular implantation of the scaffolds.Results The Gd-HA composite scaffold showed irregular void structure under electron microscope.Cell morphology observation showed that ADSCs grew adherently to the wall and were long shuttle-shaped.The positivity rate of CD29 was 96.94％,CD44 was 97.90％,CD45 was 0.10％,and CD34 was 0.46％,which was obtained using flow cytometry.Live-dead cell staining showed that the amount of live cells in the Gd-HA group was significantly better than that in the hydroxyapatite(HA)group after 5 days of co-culture.CCK-8 assay showed no significant difference in cell proliferation within 0-3 days.After 3 days,the Gd-HA group was significantly better than the HA group and the control group(P＜0.05).Calcium nodule deposition after alizarin red staining was significantly better in the Gd-HA group than in the HA and control groups,showing a deeper red color.No skin irritation was observed in gross and skin tissue HE observations after the contact of the extract with the skin.The general condition of the experimental groups was good after the infusion of the extract into the abdominal cavity,and the body mass tended to increase steadily(P＞0.05).HE staining showed that inflammatory reaction at the interface between the material and muscle tissue of the stent intramuscular implantation site in Gd-HA group was significantly higher than that of the control group,and the inflammatory cell infiltration was gradually reduced with the prolongation of implantation time.At the 8th weeks the morphology of the tissue around the material was close to normal muscle tissue,and no pathological changes were observed in the HE staining of liver and kidney at the 12th week.Conclusion Gd-HA composite scaffolds exhibit good biocompatibility and facilitate cell proliferation and osteogenic differentiation,and they are expected to serve as good carriers for stem cell transplantation in tissue engineering.