Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

Objective:To examine the prevalence of malnutrition and evaluate the impact of nutritional support on clinical outcomes in elderly patients diagnosed with gastric and colorectal cancer.Methods:A retrospective cohort study was conducted, analyzing elderly patients with gastrointestinal tumors who underwent surgical treatment in the general surgery department from January 2019 to June 2020.The Global Leadership Initiative on Malnutrition(GLIM)criteria were utilized to diagnose malnutrition, and the effects of malnutrition and nutritional support on clinical prognosis were investigated.Results:A total of 426 elderly hospitalized patients with gastric and colorectal tumors who underwent surgical treatment were included in this study.This cohort comprised 199 cases of gastric cancer and 227 cases of colorectal cancer, with ages ranging from 65 to 91 years(mean age: 72.05±5.99).According to the GLIM criteria, 43.7%(186/426)of the patients were diagnosed with malnutrition, of which 25.6%(109/426)were moderately malnourished and 18.1%(77/426)were severely malnourished.Among the gastric cancer patients, 73.4%(146/199)were identified as having nutritional risk, with 48.7%(97/199)being malnourished and 22.6%(45/199)experiencing severe malnutrition.In the colorectal cancer group, 63.9%(145/227)were at nutritional risk, 39.2%(89/227)were malnourished, and 14.1%(32/227)had severe malnutrition.Additionally, 60.3%(257/426)of the patients received nutritional support therapy: 25.4%(108/426)received parenteral nutrition(PN), 11.3%(48/426)received enteral nutrition(EN), 23.7%(101/426)received a combination of EN and PN, while 39.7%(169/426)did not receive any nutritional support.Regardless of the presence or degree of malnutrition, patients who received nutritional support had significantly shorter total hospital stays compared to those who did not receive nutritional support, and this difference was statistically significant( t=5.58, 3.69, 2.21, 3.03, all P<0.05). Conclusions:Providing nutritional support to malnourished patients can reduce the length of hospital stay and improve clinical outcomes.

Objective:To investigate the association between the metabolic score for visceral fat(METS-VF)and sarcopenia in older adults in China.Methods:A retrospective cohort study was conducted.A total of 1 262 participants aged ≥60 years old who did not diagnose with sarcopenia in 2011 and had complete follow-up data in 2015 were selected from the China health and retirement longitudinal survey(CHARLS). Participants were divided into the low METS-VF group (n=621)and the high METS-VF group (n=641), and then the corrleation between METS-VF and sarcopenia was analyzed.Results:The inverse probability of treatment weighting(IPTW)was used to balance all covariates between the low METS-VF group and high METS-VF group.The results showed that 30 participants in the low METS-VF group and 47 participants in the high METS-VF group were diagnosed with sarcopenia, with prevalence rates of 4.83%(30/621)and 7.33%(47/641), respectively.The difference in the prevalence of sarcopenia between the two groups was statistically significant after IPTW ( χ2=3.934, P=0.048, SMD=0.150). Logistic regression analysis showed that, after adjusting for various confounders, high METS-VF was significantly associated with an increased risk of sarcopenia in older adults( OR=2.130, 95% CI: 1.294~3.572, P=0.003). Subgroup analyses further indicated that individuals without cardiovascular disease had a relatively higher risk of sarcopenia( P for interaction=0.032). Conclusions:METS-VF is associated with an increased risk of sarcopenia in older adults in China, and its predictive and diagnostic value warrants further investigation.

Based on the pathogenesis of erectile dysfunction (ED) from the meridian-zangfu relationship and the "brain-heart-kidney-essence chamber" axis, it proposes that dysfunction of the "brain-heart-kidney-essence chamber" axis is closely related to the occurrence of ED. Among these, brain-heart disharmony is the key pathogenic factor, kidney deficiency and essence depletion constitute an important basis, and essence chamber stasis is a critical mechanism. The treatment approach emphasizes harmonizing the brain and heart, regulating the mind, tonifying the kidney and replenishing qi, unblocking qi and blood to harmonize the essence chamber. The primary acupoints include Baihui (GV20)-Neiguan (PC6)-Shenmen (HT7), Taixi (KI3)-Guanyuan (CV4)-Sanyinjiao (SP6), and Zhongji (CV3)-Dahe (KI12)-Gongsun (SP4), with additional acupoints selected based on syndrome differentiation. This approach aims to restore the clarity of the brain and heart, replenish kidney qi, and unblock the essence chamber, thereby facilitating the restoration of normal functions of the brain, heart, kidney, and essence chamber, and alleviating ED symptoms and improving overall clinical efficacy.
Humans ; Male ; Meridians ; Erectile Dysfunction/physiopathology* ; Kidney/physiopathology* ; Brain/physiopathology* ; Acupuncture Therapy ; Acupuncture Points ; Heart/physiopathology*

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

This study aimed to investigate the anti-inflammatory and antioxidant effects of atractylon on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Changes in lung function parameters were measured in mice after intraperitoneal administration of atractylon. Pathological changes in lung tissue were observed by H&E staining, and the degree of pulmonary edema was assessed by the lung wet/dry weight ratio (W/D). Kit assays were used to detect changes in oxidative stress markers in mouse serum and the protein concentration in bronchoalveolar lavage fluid (BALF). ELISA was employed to measure the expression levels of inflammatory cytokines in BALF and serum. Western blot was used to detect the expression levels of proteins related to the cGAS-STING pathway and vascular cell adhesion molecule-1 (VCAM-1) in lung tissue. Results showed that, compared to the ALI model group, mice in the low-dose and high-dose atractylon groups exhibited significant improvement in lung function parameters, alleviated pulmonary edema, and reduced inflammatory cell infiltration in lung tissue. Protein content and inflammatory cytokine levels in serum and BALF were decreased, while serum oxidative stress indicators were improved. Western blot results further indicated that atractylon could regulate the cGAS-STING pathway, blocking the generation of inflammatory signals, and simultaneously inhibit VCAM-1 expression, thereby reducing pulmonary vascular injury. The results suggest that atractylon may alleviate LPS-induced ALI by modulating the cGAS-STING signaling pathway, reducing the expression of pro-inflammatory cytokines and the production of pro-inflammatory mediators, and improving vascular endothelial injury. This study provides a new potential target and theoretical basis for the treatment of ALI, as well as a potential drug candidate for ALI therapy.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Varicocele is a common disease of the male reproductive system, and the pampiniform plexus in the spermatic cord manifests abnormal dilatation, extension, and circuity, which is a vasculopathy. In this article, we believe that the relevance of the essence chamber collaterals to the spermatic vein in terms of anatomical morphology and physiological function is high and that when pathogenic qi invades the essence chamber, the qi and collaterals of the essence chamber are out of harmony, the fluid collaterals are impassable, and the blood collaterals are obstrcuted, and the essence chamber collaterals are blockaded with several pathological products, and even intermingled phlegm and blood stasis in the blood collaterals and form vascular clusters, resulting in the formation and development of varicocele. Based on this, this article proposes the core treatment principle of healing, harmonizing, activating, and dredging the collaterals, with the basic treatment method of nourishing qi and harmonizing collaterals, activating blood collaterals, and dredging blood stasis to, respectively treat degree Ⅰ, Ⅱ, and Ⅲ varicocele, aiming to prevent the change of the varicocele, dredge the curvature of the varicocele, and dissipate the knots of the varicocele. The proposal of essence chamber collaterals is of great significance to understanding the common law and pathological aspects of the occurrence and development of essence collateral and vascular lesions from the perspective of integrated traditional Chinese and Western medicine.

Objective:To analyze the disease burden and changing trend of pancreatic cancer in our country from 1990 to 2021, and predict the incidence and mortality trends of pancreatic cancer from 2022 to 2036.Methods:Utilizing the data from the Global Burden of Disease 2021 Study, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and disability-adjusted life rate (DALY) of pancreatic cancer in our country from 1990 to 2021 were evaluated. DALY is calculated by adding the number of years of life lost due to pancreatic cancer to the years of life lost due to disability. The Joinpoint model was used to calculate the average annual percentage change (AAPC), the age-period-cohort model was applied to control the influence of age, period and birth cohort, and the Bayesian age-period-cohort model was used to predict the incidence and mortality trends of pancreatic cancer in our country from 2022 to 2036.Results:Compared with 1990, the data of ASIR, ASMR and age-standardized disability-adjusted life years (DALY) rates of pancreatic cancer in our country in 2021 all increased, and the increase in men was more significant than that in women. The peaks of morbidity and mortality in 1990 and 2021 were both occurred in the elderly. The incidence rate, mortality rate and changes of men in all age groups were higher than those of women. The changes in the age-standardized DALY rate were mainly reflected in the male population. The first peaks of the age-standardized DALY rate in 1990 and 2021 both occurred at the age of 70-74, and the second peak of the age-standardized DALY rate in 2021 shifted to the age of 85-89. The peak rate of age-standardized DALY in females is earlier than that in males. The AAPC of ASIR and ASMR for all genders of pancreatic cancer in our country from 1990 to 2021 was 0.72 (95% CI: 0.50-0.94, P<0.001) and 0.56 (95% CI: 0.31-0.82, P<0.001), respectively, and the difference was statistically significant. In our country men with pancreatic cancer, ASIR (AAPC=0.89, 95% CI: 0.68-1.10, P<0.001) and ASMR (AAPC=0.71, 95% CI: 0.49-0.93, P<0.001) were compared with ASIR (AAPC=0.48, 95% CI: ) in women. 0.22-0.73, P<0.001) and ASMR (AAPC=0.33, 95% CI: 0.08-0.58, P=0.010) increased rapidly, and the difference was statistically significant. The ASDR of all genders showed an upward trend (AAPC=0.36, 95% CI: 0.18-0.54, P<0.001), and the difference was statistically significant. The incidence rate and mortality rate of all genders are on the rise. When the age of the population is over 60 years old, the incidence and mortality of specific diseases show an upward trend with the delay of the birth cohort. It is expected that from 2022 to 2036, the ASIR and ASMR of both men and women will increase annuallyand eventually double. Conclusion:From 1990 to 2021, the burden of pancreatic cancer in our country has generally shown an increasing trend, and it is expected that the disease burden will further increase in the future.

A 20-year old female patient diagnosed with right distal tibial giant cell tumor underwent a surgery of resection of distal tibial giant cell tumor, residual cavity liquid nitrogen and electrocauterization inactivation and local arthroplasty on March 17, 2023. Preoperatively a life-size distal tibia model was 3D printed using polylactic acid (PLA) material based on the CT data of patient's distal tibia. Tumor resection was simulated on the model, preserving the surrounding normal bone and articular cartilage unaffected by the tumor. The residual cavity was filled with bone cement and the distal tibial articular surface was shaped using the talar articular surface as a template. The 3D CT data of bone cement was collected and reconstructed. The irregular bone and cartilage defect data were trimmed to form a regular arc shape, which was used as the data for fabricating local arthroplasty prosthesis. The local arthroplasty prosthesis composed of a titanium base and a VE polyethylene liner was 3D printed. During the operation, the test models of titanium alloy base and VE polyethylene liner were used to test the matching degree with the bone and cartilage defect. Minor adjustments were made by removing a portion of the lateral wall of the residual cavity and modifying the base height to achieve proper alignment of the distal tibial articular surface with the talar surface. After confirming a satisfactory fit, the local arthroplasty prosthesis was implanted. Intraoperative fluoroscopic confirmed accurate placement of the prosthesis, good anatomical match with the defect, and restoration of the joint line. The postoperative follow-up was conducted at 2, 4, 12, 20, 48, 72 and 92 weeks. Wound healing was closely monitored, along with radiologic assessment for prosthesis bone ingrowth and local tumor recurrence. Functional evaluations were performed using the AOFAS and Kofoed scoring systems. Postoperatively, the patient experienced plantar numbness and sensory disturbance, which gradually resolved after three weeks. Assisted ambulation began at two weeks postoperatively, and the patient resumed a normal gait by 12 weeks. The Mayo ankle arthroplasty evaluation criteria at postoperative at 48 weeks were excellent. The AOFAS score and Kofoed score were 97 points and 94 points respectively, indicating excellent functional outcomes. Postoperative X-ray indicated that no bone ingrowth was observed at 2 weeks and 4 weeks after the operation, minor ingrowth at 12 weeks postoperatively, significant bone ingrowth at 20 weeks, and complete osseointegration by 48 to 64 weeks. Postoperative CT imaging at 92 weeks confirmed full prosthesis osseointegration, while MRI at 72 weeks showed no evidence of tumor recurrence.