Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Chemotherapy is an important treatment for tumors， but most patients experience varying degrees of chemotherapy- induced myelosuppression. Four properties theory of traditional Chinese medicine （TCM） has unique advantages in improving chemotherapy-induced myelosuppression. The monomers from TCM with different properties and flavors， such as cold-natured （e.g. Scutellaria baicalensis， Rhus chinensis）， cool-natured （e.g. Ligustrum lucidum， Ophiopogon japonicus）， warm-natured （e.g. Panax ginseng， Epimedium brevicornu， Curcuma longa， Angelica sinensis）， hot-natured （e.g. Cinnamomum cassia， Aconitum carmichaeli）， and neutral-natured （e. g. donkey-hide gelatin， Lycium barbarum， Rhodiola rosea， fungi）， can exert anti- myelosuppressive effects by reducing damage to hematopoietic stem/progenitor cells， improving the bone marrow hematopoietic microenvironment， inhibiting the oxidative stress response， regulating signaling pathways， so as to ultimately repaire inflammatory damage and improve hematopoietic function， thereby playing an anti-myelosuppressive role.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

Objective:To evaluate the clinical efficacy of botulinum toxin type A (BTX-A) combined with sodium hyaluronate solution for facial microdroplet injection in improving facial skin photoaging.Methods:A prospective randomized controlled trial was conducted. From January to July 2024, patients with facial photoaging problems were recruited from the Plastic Surgery Department of the Affiliated Hospital of Xuzhou Medical University and randomly divided into a monotherapy group (sodium hyaluronate solution droplet injection) and a combination therapy group (BTX-A + sodium hyaluronate solution droplet injection) by hierarchical block randomization method. The treatment regimen was 3 months, with one treatment for each month, with a total of 3 treatment. The combination therapy group only used a combination therapy of two drugs (BTX-A 25 U+ 5 ml sodium hyaluronate solution) during the first injection. During the three treatments of the monotherapy group and the second and third treatments of the combination therapy group, 5 ml of sodium hyaluronate solution was injected as the solo ingredient. Follow up was conducted at 1, 2, and 4 months after the last treatment. Serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by test kit. Five skin texture indicators (moisture content, transepidermal water loss rate, elasticity, glossiness, and pH) were evaluated using the German CK skin tester. VISIA skin detector was used for facial two-dimensional photography and skin condition analysis. Clinical efficacy (significant improvement, obvious improvement, improvement, no improvement) and global aesthetic improvement scale (GAIS) scores on a 5-point scale were recorded. Patient satisfaction levels (very satisfied, satisfied, and dissatisfied) were investigated. The data were analyzed using SPSS 27.0 software. Count data was presented as examples and(or) percentages, and analyzed using a chi-square test. Normal distribution measurement data was represented by Mean±SD and analyzed using t-test. Results:A total of 100 patients were included, with 50 cases in each group. There were 17 males and 33 females in the monotherapy group, with an age of (31.3±7.1) years, and there were 5, 14, 29 and 2 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There were 15 males and 35 females in the combination therapy group, with an age of (32.1±8.4) years old, and there were 4, 15, 27 and 4 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There was no statistically significant difference in gender composition, age, and Glogau skin photoaging classification between the two groups (all P>0.05). One month after the first treatment, both groups showed an increase in SOD activity and a decrease in MDA levels, with more significant changes observed in the combination therapy group ( P<0.01 for both). At the follow-up of 1, 2, and 4 months after the last treatment, the combination therapy group outperformed the monotherapy group in all 5 skin texture indicators (all P<0.05). One month after the last treatment, the total effective rate of the combination therapy group was 76.0% (38/50), which were significantly higher than that of the monotherapy group’s 50.0% (25/50) ( P<0.05); in addition, the combination therapy group showed significant advantages in facial aesthetic GAIS scores, as well as patient satisfaction, with a satisfaction rate of up to 98.0% (49/50), which was higher than the 88.0% (44/50) of the monotherapy group ( P<0.01). Throughout the entire treatment process, neither group experienced serious adverse reactions. Conclusion:Facial microdroplet injection of BTX-A combined with sodium hyaluronate solution effectively improves symptoms of facial skin photoaging, enhancing skin hydration and elasticity, reducing transepidermal water loss, improving skin gloss, regulating skin pH, and enhancing skin antioxidant capacity, ultimately achieving facial skin rejuvenation. This method is safe, effective and holds high clinical relevence and patient satisfaction.

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

Objective:To evaluate the clinical efficacy of botulinum toxin type A (BTX-A) combined with sodium hyaluronate solution for facial microdroplet injection in improving facial skin photoaging.Methods:A prospective randomized controlled trial was conducted. From January to July 2024, patients with facial photoaging problems were recruited from the Plastic Surgery Department of the Affiliated Hospital of Xuzhou Medical University and randomly divided into a monotherapy group (sodium hyaluronate solution droplet injection) and a combination therapy group (BTX-A + sodium hyaluronate solution droplet injection) by hierarchical block randomization method. The treatment regimen was 3 months, with one treatment for each month, with a total of 3 treatment. The combination therapy group only used a combination therapy of two drugs (BTX-A 25 U+ 5 ml sodium hyaluronate solution) during the first injection. During the three treatments of the monotherapy group and the second and third treatments of the combination therapy group, 5 ml of sodium hyaluronate solution was injected as the solo ingredient. Follow up was conducted at 1, 2, and 4 months after the last treatment. Serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by test kit. Five skin texture indicators (moisture content, transepidermal water loss rate, elasticity, glossiness, and pH) were evaluated using the German CK skin tester. VISIA skin detector was used for facial two-dimensional photography and skin condition analysis. Clinical efficacy (significant improvement, obvious improvement, improvement, no improvement) and global aesthetic improvement scale (GAIS) scores on a 5-point scale were recorded. Patient satisfaction levels (very satisfied, satisfied, and dissatisfied) were investigated. The data were analyzed using SPSS 27.0 software. Count data was presented as examples and(or) percentages, and analyzed using a chi-square test. Normal distribution measurement data was represented by Mean±SD and analyzed using t-test. Results:A total of 100 patients were included, with 50 cases in each group. There were 17 males and 33 females in the monotherapy group, with an age of (31.3±7.1) years, and there were 5, 14, 29 and 2 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There were 15 males and 35 females in the combination therapy group, with an age of (32.1±8.4) years old, and there were 4, 15, 27 and 4 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There was no statistically significant difference in gender composition, age, and Glogau skin photoaging classification between the two groups (all P>0.05). One month after the first treatment, both groups showed an increase in SOD activity and a decrease in MDA levels, with more significant changes observed in the combination therapy group ( P<0.01 for both). At the follow-up of 1, 2, and 4 months after the last treatment, the combination therapy group outperformed the monotherapy group in all 5 skin texture indicators (all P<0.05). One month after the last treatment, the total effective rate of the combination therapy group was 76.0% (38/50), which were significantly higher than that of the monotherapy group’s 50.0% (25/50) ( P<0.05); in addition, the combination therapy group showed significant advantages in facial aesthetic GAIS scores, as well as patient satisfaction, with a satisfaction rate of up to 98.0% (49/50), which was higher than the 88.0% (44/50) of the monotherapy group ( P<0.01). Throughout the entire treatment process, neither group experienced serious adverse reactions. Conclusion:Facial microdroplet injection of BTX-A combined with sodium hyaluronate solution effectively improves symptoms of facial skin photoaging, enhancing skin hydration and elasticity, reducing transepidermal water loss, improving skin gloss, regulating skin pH, and enhancing skin antioxidant capacity, ultimately achieving facial skin rejuvenation. This method is safe, effective and holds high clinical relevence and patient satisfaction.

Objective:To investigate the effect of rat platelet-rich plasma (PRP) gel on autologous adipose-derived mesenchymal stem cells (ADSCs) overexpressing glial-derived neurotrophic factor (GDNF).Methods:This study was an experimental study. Five adult male Sprague-Dawley rats were used, and the primary ADSCs were obtained by collagenase digestion, and then the cells were identified successfully. The 3 rd passage of ADSCs were obtained and divided into negative control group infected with unloaded adenovirus and overexpressing GDNF group infected with overexpressing GDNF adenovirus, according to random number table method (the grouping method was the same below). After 48 hours of culture, the infection of cells was observed. Five adult male Sprague-Dawley rats were used, and the PRP was obtained after collecting blood by differential centrifugation. PRP was prepared into a gel and its microstructure was observed by scanning electron microscope. The ADSCs of 3 rd passage were added into the PRP solution mixture and cultured for 48 hours after gelation. The cell growth was observed by hematoxylin-eosin staining and calcein/propyl iodide staining. ADSCs infected with unloaded adenovirus and ADSCs infected with overexpressing GDNF adenovirus were routinely cultured in PRP gel. After 48 hours of culture, the cell growth was detected by calcein/propyl iodide staining. After culture for 24, 48, 72 hours and 1, 2, 3, 4 weeks, the supernatant of cell culture medium was collected, the absorbance value was determined by microplate analyzer, and the GDNF content was calculated, with the sample number of 3. After 48 hours of culture, the expression of S100 protein (a specific marker of Schwann cells) was detected by immunofluorescence assay. Results:After 48 hours of culture, the proportions of cells infected with adenovirus in negative control group and overexpressing GDNF group were close to 90%, and the cell growth was good. The cells in negative control group grew normally. The morphology of the cells in overexpressing GDNF group changed significantly with 80%-90% of the cells having two or more protrusions, and the protrusions were interwoven to form a network wherever the cells gathered. PRP gel formed a three-dimensional network structure with different pore sizes. After 48 hours of culture, ADSCs could be well attached to PRP gel, and 98% of the cells were alive. After 48 hours of culture, ADSCs infected with unloaded adenovirus grew well and showed typical ADSC-like spindle-shaped growth. ADSCs infected with overexpressing GDNF adenovirus grew well, and most of the cells had two or more protrusions, and the protrusions were interwoven into a network. After culture for 24, 48, 72 hours and 1, 2, 3, 4 weeks, the content of GDNF in the supernatant of ADSCs infected with overexpressing GDNF adenovirus was (90±10), (133±15), (150±10), (137±15), (132±18), (120±10), and (127±16) pg/mL, which was significantly higher than (42±7), (44±7), (43±6), (47±6), (49±5), (49±6), and (51±4) pg/mL of ADSCs infected with unloaded adenovirus (with t values of 6.20, 8.08, 15.18, 9.12, 7.99, 9.61, and 7.86, respectively, P<0.05). After 48 hours of culture, the fluorescence intensity of S100 protein expression of ADSCs infected with overexpressing GDNF adenovirus was significantly stronger than that of ADSCs infected with unloaded adenovirus. Conclusions:The prepared autologous three-dimensional PRP gel has good biocompatibility and can carry rat GDNF-overexpressing ADSCs and release GDNF slowly, inducing ADSCs to differentiate into Schwann cells that express high level of S100 protein.

Objective:To utilize a deep learning approach based on speech to distinguish between depressive and manic mood states in patients with bipolar disorder (BD).Methods:Sixty-one BD patients who visited the outpatient department of psychiatry at Peking University Sixth Hospital were recruited to participate in the study from June 2018 to March 2022. Quick Inventory of Depressive Symptomatology, Mood Disorder Questionnaire and Young Mania Rating Scale were used to determine patients′ mood states. The voices of the patients were recorded, including 190 samples during the patient′s remission, depressive, and manic mood period respectively. A total of 136 features were extracted from the voice samples, including Mel-frequency cepstral coefficients and zero-crossing rates using the speech analysis library in Python. A LIGHT-SERNET-based network was then used to train a model for emotion classification. Accuracy is used to evaluate the performance of the model, using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic curve (ROC) to evaluate the predictive results of model for three mood states. Kruskal-Wallis H tests or χ 2 tests were conducted to compare the differences among the demographic information of three groups. Results:There were statistically significant differences among the three groups in age ( H=25.83, P<0.001), years of education ( H=25.25, P<0.001) and marital status (χ 2=23.81, P<0.001). There is no significant difference in gender (χ 2=4.63, P=0.099). The accuracy of the model in detecting the three emotional states was 0.84. The sensitivity and specificity in detecting remission were 0.88 and 0.93, respectively, and the positive predictive value and negative predictive value were 0.87 and 0.94, respectively. The sensitivity and specificity in detecting depressive episodes were 0.82 and 0.92, respectively, and the positive predictive value and negative predictive value were 0.84 and 0.92, respectively. The sensitivity and specificity in detecting manic episodes were 0.82 and 0.91, respectively, and the positive predictive value and negative predictive value were 0.83 and 0.91, respectively. The areas of the receiver operation characteristic curve for the three mood states were similar and all exceeded 0.90. Conclusion:The LIGHT-SERNET-based deep learning model shows good discrimination ability between depressive and manic mood states based on speech analysis.