ObjectiveThis study aims to investigate the therapeutic effects of Wenyang Xiaoyin Prescription （Linggui Zhugan Tang combined with Tingli Dazao Xiefei Tang） on a doxorubicin-induced mouse model of chronic heart failure （CHF）. The multi-targeting action mechanism of the therapy is revealed， based on the arginine vasopressin （AVP）-vasopressin V₂ receptor （V2R）-aquaporin 2 （AQP2） signaling pathway and nuclear transcription factor -κB （NF-κB） pathway mediated by the liver X receptor （LXR） in the heart， brain， and kidney tissue. MethodsCHF mouse models were established by using intraperitoneal injection of doxorubicin and subsequently divided into a blank control group， a model control group， Wenyang Xiaoyin Prescription groups （Linggui Zhugan decoction combined with Tingli Dazao Xiefei decoction） with various doses， a captopril group， and a combination group receiving both Wenyang Xiaoyin prescription （as before） and captopril. Cardiac function was assessed by using color Doppler echocardiography， while the levels of brain natriuretic peptide （BNP）， AVP， and the renin-angiotensin-aldosterone system （RAAS） in the serum were measured via enzyme-linked immunosorbent assay （ELISA）. Pathological changes and ventricular remodeling in ventricular tissues were evaluated through hematoxylin and eosin （HE） and Masson staining， and myocardial cell apoptosis of mice was assessed by using TdT-mediated dUTP Nick-End Labeling （TUNEL） staining. Western blot and real-time polymerase chain reaction （Real-time PCR） were employed to detect the protein and RNA expression levels of LXRα， nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS） in the cardiac tissue， LXRβ， AVP in the hypothalamus， and LXRβ， V2R， and AQP2 in the kidneys. Furthermore， immunohistochemistry was used to quantify AQP2-positive collecting ducts in renal tissues. ResultsThe Wenyang Xiaoyin prescription significantly enhanced cardiac function indicators in CHF mice， reducing levels of BNP， AVP， and RAAS in the serum. It also mitigated myocardial cell damage and fibrosis change. The Wenyang Xiaoyin prescription inhibited the expressions of NF-κB and its downstream targets TNF-α and iNOS and improved myocardial inflammatory response， cell apoptosis， and ventricular remodeling by upregulating the expression of LXRα in cardiac tissues. Concurrently， the Wenyang Xiaoyin prescription elevated LXRβ expression in the kidneys and hypothalamus while downregulating the expression levels of AVP， V2R， and AQP2， as well as water permeability in the collecting ducts， thereby alleviating cardiac load. ConclusionThe intervention of Wenyang Xiaoyin prescription demonstrates a significant therapeutic effect on CHF， and its role involves the multi-target effect mechanism of the AVP/V2R/AQP2 and NF-κB pathways mediated by the nuclear receptor LXR in the heart， brain， and kidney tissue.

ObjectiveTo study the relationship between qi stagnation constitution and suboptimal health status (SHS) or lifestyle.MethodsFrom 2012 to 2013, we conducted a cross-sectional survey of 24 159 Chinese individuals aged 12–80 years. The qi stagnation constitution was assessed using the Constitution in Chinese Medicine Questionnaire. Health status was evaluated through medical records and the Subhealth Measurement Scale V1.0 (SHMS V1.0). Health-promoting lifestyles were measured using the Health-Promoting Lifestyle Profile II (HPLP-II).ResultsOf the 24 159 participants, 16.1% and 15.2% were classified as “always” and “sometimes” having the qi stagnation constitution, respectively. Those classified as “rarely” having the qi stagnation constitution scored higher on both the HPLP-II and SHMS V1.0. The participants classified as “always” having the qi stagnation constitution showed a significant association with SHS or disease compared to other imbalanced constitutions. Those in the “always” category were approximately 21 times more likely to be classified as having SHS (odds ratio [OR]: 21.17, 95% confidence interval [CI]: 15.74–28.45), whereas those in the “sometimes” category were approximately six times more likely (OR: 5.89, 95% CI: 5.04–6.90). Accordingly, the qi stagnation constitution score was significantly associated with the diagnosis of SHS, with an area under the curve of 0.77 (P .001). A score of 18.75 yielded the highest Youden Index (0.407), with a sensitivity of 60.5% and a specificity of 80.3%. Significant associations were observed between health-promoting lifestyles and qi stagnation constitution severity in an ordinal regression analysis (P .001). Protective factors included stress management (OR: 1.59), self-actualization (OR: 1.57), and exercise (OR: 1.36). In contrast, poorer interpersonal relationships (OR: 0.79), greater health responsibilities (OR: 0.86), and poorer nutrition (OR: 0.91) were associated with increased severity.ConclusionModulating the qi stagnation constitution through lifestyle interventions may help prevent the progression of SHS to disease, which aligns with core preventive principles in traditional Chinese medicine.

ObjectiveTo explore the clinical efficacy and safety of the combination of Erchentang and Bixie Fenqingyin in the treatment of patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome to provide a new method and evidence for the treatment of acute cerebral infarction with hyperuricemia. MethodA total of 132 eligible patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome admitted to the Putuo Hospital of Shanghai University of Traditional Chinese Medicine（TCM） from May 2021 to May 2022 were randomly divided into a Chinese medicine group， a western medicine group， and a control group， with 44 cases in each group. All three groups received routine western medical treatment for acute cerebral infarction. Additionally， the Chinese medicine group received Erchentang combined with Bixie Fenqingyin， the western medicine group received Benzbromarone tablets， and the control group did not receive any uric acid-lowering treatment. The treatment duration was four weeks. The modified Rankin Scale （mRS） score after three months of onset， as well as the National Institutes of Health Stroke Scale （NIHSS） scores， TCM syndrome scores， serum uric acid （SUA） levels， serum C-reactive protein （CRP） and interleukin-6 （IL-6） levels， serum superoxide dismutase （SOD） and malondialdehyde （MDA） levels， and other safety indicators were observed before and after treatment. ResultA total of 129 cases completed the trial observation， with 43 cases in the Chinese medicine group， 42 cases in the western medicine group， and 44 cases in the control group. The rate of good prognosis in the Chinese medicine group （83.7%，36/43） was higher than that in the western medicine group （64.3%，27/42） and the control group （40.9%，18/44） （χ²=4.184，16.930，P<0.05）， and the western medicine group was superior to the control group （χ²=4.707，P<0.05）. After treatment， the NIHSS scores， TCM syndrome scores， SUA， CRP， IL-6， and MDA levels of the patients in all three groups decreased， while the SOD levels increased compared with those before treatment （P<0.05）. Among them， the improvement in NIHSS score was better in the Chinese medicine group and the western medicine group than in the control group （P<0.05）. The Chinese medicine group showed the greatest improvement in TCM syndrome （P<0.05）， while the western medicine group showed the greatest reduction in uric acid levels （P<0.05）. No significant abnormalities in safety indicators were observed before and after treatment in the three groups， and no serious adverse reactions were reported. ConclusionThe combination of Erchentang and Bixie Fenqingyin can significantly improve the prognosis， early neurological deficits， and TCM syndromes of patients acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome. It can also lower uric acid levels and inhibit inflammatory and oxidative stress reactions.

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Objective:To investigate the effect and safety of rituximab, programmed death 1 (PD-1) monoclonal antibody, and Bruton tyrosine kinase (BTK) inhibitor on elderly refractory primary central nervous system lymphoma (PCNSL).Methods:The clinical data of an elderly patient with refractory PCNSL treated with the combination of rituximab, PD-1 monoclonal antibody and BTK inhibitor in the First Hospital of Jilin University in February 2020 were retrospectively analyzed. The relevant literature was reviewed.Results:The patient had primary central nervous system diffuse large B-cell lymphoma (high-risk group), and the Memorial Sloan Kettering Cancer Center (MSKCC) score was 2 (estimated overall survival time was 7 months). Disease progressed after 1 course of treatment. Complete remission was achieved after the therapy of rituximab, PD-1 monoclonal antibody combined with BTK inhibitor. PD-1 monoclonal antibody maintenance therapy was performed and patient was followed up until November 17, 2021. The patient's condition was stable. The second progression-free survival (PFS) time was 20 months, and the overall survival time was 21 months. The patient well tolerated the new drug treatment, and no adverse reactions of grade 3 or above occurred.Conclusions:The new targeted combination therapy can be used as a treatment option for elderly PCNSL patients, which can further improve the curative effect and significantly improve the prognosis.

Objective:To explore immune cell reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT)by using mathematical function models.Methods:From June 2011 to May 2015, 65 patients with malignant hematological disorders were retrospectively analyzed. Immune cell frequencies and absolute counts were detected at day 14/28/42 and month 2/3/6/9/12/18/24 post-allo-HSCT. The immune cells included CD3 + T, CD4 + helper T, CD8 + effector T, regulatory T, CD19 + B, CD3 -CD56 + NK and CD3 + CD56 + NKT. Kinetic curve models and mathematical equations were established by utilizing curve model estimation. Results:Cubic curve models were observed for the changes of immune cell frequencies. Except for CD3 + T, CD8 + T and NK cells, the changes of absolute counts of immune cells conformed to cubic curve models. The reconstructed kinetic models of CD8 + T and NK cells after allo-HSCT were associated with relapse. Conclusions:Immune cell reconstitution after allo-HSCT conforms to certain mathematical function curve models. It may provide a new strategy for in-depth studies of immune reconstitution after allo-HSCT.

Objective To discuss the dosimetric advantage of computed tomography-guided interstitial brachytherapy compared with the conventional intracavitary brachytherapy for locally advanced cervical cancer,offering a more advantageous clinical treatment approach. Methods Twenty-eight locally advanced cervical cancer patients with bulky tumors ( tumor size>5 cm) after external beam radiotherapy received computed tomography-guided interstitial brachytherapy. Dosimetric outcomes of the current study, including the total dose ( external beam radiotherapy+ brachytherapy ) D90 for the HR-CTV and D2cc for the bladder,rectum, and sigmoid, were compared with a former patient group consisting of 30 patients who received the conventional intracavitary brachytherapy ( uterine tandem+ ovoid pairs ) . Results The mean D90 value for HR-CTV in the intracavitary brachytherapy group and interstitial brachytherapy group were (76.9±5. 7) and ( 88.1± 3. 3) Gy, respectively. The D2cc for the bladder, rectum, and sigmoid in the intracavitary brachytherapy group and interstitial brachytherapy group were (84.7±6. 8) Gy,(69.2±4. 2) Gy,(67.8±4. 5) Gy and (81.8±6. 5) Gy,(6.8±4. 0) Gy,(64.8±4. 1) Gy,respectively.1-year local tumor control rate in the intracavitary brachytherapy group and interstitial brachytherapy group were 59. 3％ and 85. 2％, respectively. Conclusions CT-guided interstitial brachytherapy shows a significant dosimetric advantage compared with the conventional intracavitary brachytherapy, and is, thereby, clinically possible feasible. However,the long term curative effect and toxicity need to be further investigated.

Objective To analyze the dosimetric advantages of CT-guided interstitial brachytherapy for recurrent cervical cancer. Methods A total of 16 patients with recurrent cervical cancer after radical surgery and adjuvant external beam radiotherapy received interstitial brachytherapy with CT-guided implantation of metal needles. The high-risk clinical target volume (HR-CTV) was given 36 Gy in 6 fractions.D90for HR-CTV in the brachytherapy and the cumulative D2 cm3values for the bladder,rectum,and sigmoid colon in the previous external beam radiotherapy and the brachytherapy were analyzed.Results The mean D90value for HR-CTV was 52.5±3.3 Gy. The cumulative D2 cm3values for the bladder, rectum, and sigmoid colon were 85.6±5.8 Gy,71.6±6.4 Gy,and 69.6±5.9 Gy,respectively.The mean number of metal needles was 6.1±1.5 in each brachytherapy. The actual 1-year overall survival and local control were 81% and 69%, respectively. Conclusions CT-guided interstitial brachytherapy for recurrent cervical cancer shows good dose-volume histogram parameters and few complications, so it may be clinically feasible. However,its long-term clinical efficacy needs further observation.