Homeobox(HOX)genes encode a group of proteins that are highly conserved and closely related to the axial differentiation of embryos.The disorder of segmental development caused by HOX genes deficiency or abnormal expression has been observed in drosophila and mice.However,subsequent studies have found that proteins encoded by the HOX gene family are also involved in the regulation of tumor genesis and development.The roles of the whole HOX family had been reviewed by the author in the past,and through the in-depth researches,the author paid attention to the pivotal role of HOXB9 and made new progress in the study of post-translational modifications of this protein.Taking HOXB9 as a clue,this review summarizes the tumor-related signaling pathways and the modulating effects of post-translational modification of HOXB9 on tumor progression,as well as the possible research directions in the future.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE To investigate the efficacy of Ningmitai Capsules combined with cefoperazone/sulbactam on the treatment of type 2 diabetes mellitus(T2DM)complicated with urinary tract infections(UTIs)and its impact on soluble triggering receptor expressed on myeloid cells-1(sTREM-1),microRNA(miRNA)-34 b and Toll-like receptor-4(TLR4),so as to provide a new combined regimen for clinical treatment of such patients.METHODS From May 2022 to May 2024,122 patients with T2DM complicated with UTIs treated at the Affiliated People's Hospital of Shandong First Medical University were randomly divided into a conventional group and a combination group by the odd-even randomization method,with 61 cases in each group.The conventional group was treated with cefoperazone/sulbactam,whereas the combination group received Ningmitai capsules in combination with cef-operazone/sulbactam.The efficacy,improvement time of related symptoms,T lymphocyte subsets(CD3+,CD4+,CD4+/CD8+),sTREM-1,miRNA-34b,TLR4 levels and occurrence of adverse reactions were compared between the two groups.RESULTS The total effective rate in the combination group was higher than that in the conventional group after treatment(93.44%vs.80.33%,χ2=4.604,P=0.032).There were statistically signifi-cant differences between the two groups in the time for urine routine to return to normal,disappearance of urinary irritation symptoms,conversion of urine pathogens to negative and defervescence(P<0.05).After treatment,the levels of CD3+,CD4+and CD4+/CD8+in both groups were lower than those before treatment(P<0.05),and the levels in the combination group were higher than those in the conventional group(P<0.05).Moreover,the levels of sTREM-1,miRNA-34b and TLR4 in both groups decreased after treatment(P<0.05),and the levels in the combination group were lower than those in the conventional group(P<0.05).During the treatment period,no severe adverse reactions were observed in either group,and laboratory test results for blood routine and hepatic and renal functions showed no abnormalities.CONCLUSION The application of Ningmitai capsules combined with cef-operazone/sulbactam in the treatment of T2DM complicated with UTIs has good efficacy,can effectively control infec-tions,shorten the time for symptom relief,improve immune function and attenuate inflammation level with high safety.

OBJECTIVE To investigate the efficacy of Ningmitai Capsules combined with cefoperazone/sulbactam on the treatment of type 2 diabetes mellitus(T2DM)complicated with urinary tract infections(UTIs)and its impact on soluble triggering receptor expressed on myeloid cells-1(sTREM-1),microRNA(miRNA)-34 b and Toll-like receptor-4(TLR4),so as to provide a new combined regimen for clinical treatment of such patients.METHODS From May 2022 to May 2024,122 patients with T2DM complicated with UTIs treated at the Affiliated People's Hospital of Shandong First Medical University were randomly divided into a conventional group and a combination group by the odd-even randomization method,with 61 cases in each group.The conventional group was treated with cefoperazone/sulbactam,whereas the combination group received Ningmitai capsules in combination with cef-operazone/sulbactam.The efficacy,improvement time of related symptoms,T lymphocyte subsets(CD3+,CD4+,CD4+/CD8+),sTREM-1,miRNA-34b,TLR4 levels and occurrence of adverse reactions were compared between the two groups.RESULTS The total effective rate in the combination group was higher than that in the conventional group after treatment(93.44%vs.80.33%,χ2=4.604,P=0.032).There were statistically signifi-cant differences between the two groups in the time for urine routine to return to normal,disappearance of urinary irritation symptoms,conversion of urine pathogens to negative and defervescence(P<0.05).After treatment,the levels of CD3+,CD4+and CD4+/CD8+in both groups were lower than those before treatment(P<0.05),and the levels in the combination group were higher than those in the conventional group(P<0.05).Moreover,the levels of sTREM-1,miRNA-34b and TLR4 in both groups decreased after treatment(P<0.05),and the levels in the combination group were lower than those in the conventional group(P<0.05).During the treatment period,no severe adverse reactions were observed in either group,and laboratory test results for blood routine and hepatic and renal functions showed no abnormalities.CONCLUSION The application of Ningmitai capsules combined with cef-operazone/sulbactam in the treatment of T2DM complicated with UTIs has good efficacy,can effectively control infec-tions,shorten the time for symptom relief,improve immune function and attenuate inflammation level with high safety.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.

Osteoarthritis(OA),characterized by cartilage degeneration,synovial inflammation,and subchondral bone remodeling,is among the most common musculoskeletal disorders globally in people over 60 years of age.The initiation and progression of OA involves the abnormal metabolism of chondrocytes as an important pathogenic process.Cartilage degeneration features mitochondrial dysfunction as one of the important causative factors of abnormal chondrocyte metabolism.Therefore,maintaining mitochondrial homeostasis is an important strategy to mitigate OA.Mitophagy is a vital process for autophagosomes to target,engulf,and remove damaged and dysfunctional mitochondria,thereby maintaining mitochondrial homeostasis.Cumulative studies have revealed a strong association between mitophagy and OA,suggesting that the regulation of mitophagy may be a novel therapeutic direction for OA.By reviewing the literature on mitophagy and OA published in recent years,this paper elaborates the potential mechanism of mitophagy regulating OA,thus providing a theoretical basis for studies related to mitophagy to develop new treatment options for OA.

The endoplasmic reticulum is a key site for protein production and quality control.More than one-third of proteins are synthesized and folded into the correct three-dimensional conformation in the endoplasmic reticulum.However,during protein folding,unfolded and/or misfolded proteins are prone to occur,which may lead to endoplasmic reticulum stress.Organisms can monitor the quality of the proteins produced by endoplasmic reticulum quality control(ERQC)and endoplasmic reticulum-associated degradation(ERAD),which maintain endoplasmic reticulum protein homeostasis by degrading abnormally folded proteins.The underlying mechanisms of protein folding and ERAD in mammals have not yet been fully explored.Therefore,this paper reviews the process and function of protein folding and ERAD in mammalian cells,in order to help clinicians better understand the mechanism of ERAD and to provide a scientific reference for the treatment of diseases caused by abnormal ERAD.

Objective To investigate the clinical effect of dual incision and dual plate internal fixation for the treatment of tibial plateau fractures in the elderly and its impact on knee joint function.Methods Using retrospective analysis method,103 elderly patients with tibial plateau fractures admitted to Rugao Hospital affiliated to Nantong University from April 2015 to May 2021 were selected for clinical research.According to the surgical method,they were divided into two groups,52 patients in the study group were treated with double incision double plates,and 51 patients in the control group were treated with locking plate internal fixation.Perioperative indicators,knee function,knee stability Knee joint complications.Results The hospitalization time of the study group was(7.8±2.0)days,and that of the control group was(10.0±2.4)days,and the difference was statistically significant between the two groups(P＜0.05).The HSS scores at 3 months,6 months and 12 months were(66.9±5.4),(78.4±6.6)and(83.8±6.1)in the study group,and(64.2±6.1),(74.0±7.3)and(82.0±6.8)in the control group,respectively.There was statistical significance in HSS scores 3 months and 6 months after operation between the two groups(P＜0.05).The tibial migration distance 3 months after operation was(2.54±0.50)mm in the study group and(2.84±0.67)mm in the control group,and the difference was statistically significant(P＜0.05).The knee posterior inclination angles of the study group were(4.12±1.10)°,(5.03±0.96)° and(5.46±1.52)° at 3 months,6 months and 12 months after surgery,respectively,while those of the control group were(6.11±1.43)°,(6.67±1.54)° and(7.50±1.88)°,respectively.The difference was statistically significant(P＜0.05).The activity of the study group at 3 months and 6 months after surgery was(104.3±8.2)° and(117.4±7.6)°,respectively,while that of the control group was(96.8±8.9)° and(111.8±8.2)°,and the difference was statistically significant(P＜0.05).There were 3 cases of postoperative complications in the study group and 10 cases in the control group,and the difference was statistically significant(P＜0.05).Conclusion The clinical effect of dual incision and dual plate internal fixation in the treatment of tibial plateau fractures in the elderly is affirmative,which is more beneficial for promoting early recovery of knee function and maintaining stability of knee function than locking plate internal fixation.

A liquid chromatography-tandem mass spectrometry method was established and validated for determining the concentrations of costunolide(CO), piperine(PI), agarotetrol(AG), glycyrrhizic acid(GL), vanillic acid(VA), and glycyrrhetinic acid(GA) in rat plasma. This method was then applied to the toxicokinetic study of these six compounds in rats with chronic cerebral ischemia(CCI) following multiple oral doses of Zhachong Shisanwei Pills. Finally, the effects of continuous multiple-dose administration of Zhachong Shisanwei Pills on the liver of CCI rats were investigated. The results showed that after oral administration of different doses of Zhachong Shisanwei Pills, the in vivo exposure of AG, VA, and GA was relatively high, with AUC_(0-∞) values ranging from 604.0-2 494.2, 1 305.4-4 634.5, and 2 177.5-4 045.7 h·ng·mL~(-1), respectively, while the exposure of CO, PI, and GL was relatively low, with AUC_(0-∞) values ranging from 37.8-238.2, 2.4-17.0, and 146.9-408.5 h·ng·mL~(-1), respectively. The C_(max) and AUC_(0-∞) of the six compounds were positively correlated with the administered dose. The T_(max) of PI and AG ranged from 0.3 to 2.0 h, their T_(1/2) ranged from 0.8 to 2.9 h, and their mean residence time(MRT) ranged from 1.0 to 3.7 h. The T_(max) of GL and VA was shorter(0.4-1.9 h), while their T_(1/2)(2.6-5.9 h) and MRT(2.5-8.5 h) were longer. Both CO and GA exhibited a bimodal phenomenon, with T_(max) ranging from 1.6 to 6.6 h, T_(1/2) ranging from 2.8 to 7.7 h, and MRT ranging from 4.1 to 12.9 h. Liver histopathology after 28 days of continuous multiple-dose administration of Zhachong Shisanwei Pills showed that the liver tissue remained normal at a low dose(crude drug 0.8 g·kg~(-1), approximately 5 times the clinical equivalent dose). However, as the dose increased(crude drug 1.1-3.0 g·kg~(-1), 6.9-18.8 times the clinical equivalent dose), varying degrees of liver damage were observed. Blood biochemical tests revealed no significant changes in the serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid(TBA) in CCI rats from administration groups 1 to 3(crude drug 0.8, 1.1, 1.5 g·kg~(-1)). However, ALT, AST, ALP, and TBA levels in groups 4 and 5(crude drug 2.1, 3.0 g·kg~(-1)) showed significant increases. This study preliminarily elucidated the toxicokinetic characteristics of the six compounds in Zhachong Shisanwei Pills and their effects on liver tissue in CCI rats, providing data as a reference for clinical use.
Animals ; Tandem Mass Spectrometry/methods* ; Rats ; Drugs, Chinese Herbal/toxicity* ; Male ; Rats, Sprague-Dawley ; Brain Ischemia/blood* ; Chromatography, Liquid/methods* ; Polyunsaturated Alkamides/blood* ; Piperidines/toxicity* ; Benzodioxoles/toxicity* ; Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry