Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

Objective To investigate the correlation between serum galectin-3(Gal-3),fibroblast growth factor-21(FGF-21)and the lung function and and the Modified British Medical Research Council dyspnea in-dex(mMRC)score in invalids with chronic obstructive pulmonary disease(COPD).Methods A total of 79 patients with COPD who received treatment in the hospital from April 2021 to April 2023 were selected as the observation group,and 60 healthy individuals in the hospital during the same period were selected as control group.The expressions of Gal-3 and FGF-21 in serum were detected and compared.The first second forced ex-piratory volume(FEV1),FEV1/forced vital capacity(FVC)and mMRC score in two groups were compared,and the correlation between the expression levels of Gal-3 and FGF-21 and FEV1,FEV1/FVC and mMRC score in COPD patients was analyzed.Results The expression levels of serum Gal-3 and FGF-21 in the obser-vation group were higher than those in the control group(P＜0.05).The pulmonary function indexes in ser-um of observation group were higher than those in the control group,while the mMRC score was lower than that in the control group(P＜0.05).The expression levels of Gal-3 and FGF-21 were positively correlated with FEV1 and FEV1/FVC(P＜0.05),was negatively correlated with mMRC score(P＜0.05).Conclusion The expression of serum Gal-3 and FGF-21 in COPD invalids is abnormal,and the expression levels of serum Gal-3 and FGF-21 in COPD patients were correlated with FEV1,FEV1/FVC and mMRC score,which could be used as important reference indicators for diagnosis and disease evaluation of COPD.

OBJECTIVE: To evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities. METHODS: The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score. RESULTS: There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05). CONCLUSION Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Robotic Surgical Procedures/methods* ; Male ; Female ; Retrospective Studies ; Range of Motion, Articular ; Middle Aged ; Aged ; Treatment Outcome ; Osteotomy/methods* ; Knee Joint/physiopathology* ; Operative Time

OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Objective:To explore the clinical efficacy of periosteal induction technique combined with transfer of sural neurovascular flap in treatment of post-traumatic osteomyelitis of calcaneus with soft tissue defect.Methods:Clinical data, from January 2017 to December 2022, of 17 patients in the Army Institute for Traumatic Orthopaedics, the 920th Hospital of Joint Service Force of the Chinese People’s Liberation Amy with post-traumatic calcaneal osteomyelitis combined with soft tissue defect were retrospectively studied. The patients were 11 males and 6 females, with 46.5 (17-68) years in average. All patients received surgical treatment with periosteal induction technique in 2 phased surgies. Thorough debridement, antibiotics blended bone cement filling and wound coverage with sural neurovascular flap were carried out in phase-I surgery; The phase-II surgery were performed at 6-8 weeks after infection control to remove bone cement and then to transfer bone grafts for periosteal induction. After surgery, flap healing and infection control were observed. The infection control, pain improvement, recovery of ankle function and improvement of quality of life were evaluated by comparison of following parameters before and after surgery per phase: infection indicators [white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], Visual Analogue Scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and MOS 36-item Short form Health Survey (SF-36, Boston Institute of Health, USA).Results:All 17 patients completed the two-phased surgical treatment, with an average interval of 9.4 (8-16) weeks between phase-I and phase-II surgery. All patients were included in the postoperative follow-up of 25.8 (13-40) months. After debridement in phase-I surgery, the sizes of soft tissue defect were found at 3.0 cm×2.0 cm-6.0 cm×8.0 cm. All flaps survived from the reconstructive surgery of sural neurovascular flap. Postoperative distal flap necroses occurred to 4 patients but all healed after further debridement. Recurrence of postoperative infection occurred to 2 patients and the infection control was achieved after the phase-I rescue surgery. Good outcomes without recurrence of infection were achieved after phase-II surgery. The postoperative follow-up at 1 year after phase-II surgery showed a statistically significant improvement of infection in blood indicators and reductions in VAS score, AOFAS ankle-hindfoot score and SF-36 score in comparison with those before surgery ( P<0.05). In addition to WBC, there were also significant differences in pairwise comparisons between each group at different time points ( P<0.05). Conclusion:In the treatment of post-traumatic calcaneal osteomyelitis with soft tissue defect, a combination of periosteal induction technique and sural neurovascular flap is beneficial to infection control, bone defect reconstruction, recovery of ankle function and improvement of quality of life.

Objective:To explore the clinical outcomes and recent follow-up results of the Modified Diamond Protocol in patients with low ejection fraction heart failure (HF) during the perioperative period of cardiac surgery.Methods:Retrospectively collected clinical data of 62 patients who underwent open heart surgery in the cardiac surgery department of Nanjing Drum Tower Hospital from August 2022 to January 2024, including 48 males and 14 females with mean age of (63.3±11.5)years old. All patients were diagnosed with low ejection fraction heart failure preoperatively, with left ventricular ejection fraction (LVEF) ≤0.35. Based on the indications of postoperative heart failure medication, 21 patients who received the Modified Diamond Protocol treatment were included in the Modified group, and 41 patients who received the standard treatment plan were included in the Control group. The baseline clinical characteristics and data of the two groups were compared. The left ventricular end-diastolic diameter (LVDd), pulmonary artery pressure (PH), LVEF, postoperative heart failure improvement, mortality, and readmission rates at preoperative, postoperative, and final discharge follow-up times of the two groups were analyzed.Results:There was no statistical difference in baseline data between the control group and the modified diamond regimen group ( P>0.05). There were no perioperative deaths in either group of patients. Compared to preoperative levels, there were significant decrease in PH, a significant reduction in LVDd, and significant increase in LVEF within each group ( P<0.05). Compared to control group, the Modified group demonstrated a greater reduction in PH (-17 mmHg vs. -12 mmHg, 1 mmHg=0.133 kPa), a greater reduction in LVDd (-0.59 mm vs. -0.57 mm), and a greater increase in LVEF (0.08 vs. 0.03), indicating an overall better improvement in cardiac function in the Modified group. However, there were no statistically significant differences between two groups ( P>0.05). All patients were followed up for 3-12 months. The overall mortality rate within 1 year was 12.9%(8/62). During the final follow-up for cardiac function, when comparing within each group, both groups showed a decrease in PH, a reduction in LVDd, and an increase in LVEF, all of which were improvements compared to preoperative levels, with statistically significant differences( P<0.05). Compared to control group, the Modified group showed a greater decrease in pulmonary hypertension (PH) (-17 mmHg vs. -12 mmHg), a greater reduction in LVDd(-0.58 mm vs. -0.57 mm), and a greater increase in left ventricular ejection fraction (LVEF) (0.06 vs. 0.07). The overall improvement in cardiac function was similar between the two groups, with no statistically significant differences( P>0.05). The readmission rate in the Modified group was significantly lower than in the Control group (9.5% vs. 36.6%, P=0.02), and the mortality rate was relatively lower (4.8% vs. 19.5%, P=0.11). Conclusion:The Modified Diamond Protocol is an effective approach to enhance postoperative cardiac function in patients with low ejection fraction undergoing cardiac surgery, contributing to early recovery and reduced readmission rates, but the long-term trend in mortality rates remain to be observed.

Non-alcoholic fatty liver disease(NAFLD)is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes.If not intervened in time,NAFLD may develop into liver fibrosis or liver cancer,and ultimately threatening life.NAFLD has complicated etiology and pathogenesis,and there are no effective therapeutic means and specific drugs.Currently,insulin sensitizers,lipid-lowering agents and hep-atoprotective agents are often used for clinical intervention,but these drugs have obvious side effects,and their effectiveness and safety need to be further confirmed.Adenosine monophosphate(AMP)-activated protein kinase(AMPK)plays a central role in maintaining energy homeostasis.Activated AMPK can enhance lipid degradation,alleviate insulin resistance(IR),suppress oxidative stress and inflammatory response,and regulate autophagy,thereby alleviating NAFLD.Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects.In this article,we reviewed the biologically active natural herbal medicines(such as natural herbal medicine formulas,extracts,polysaccharides,and monomers)that reported in recent years to treat NAFLD via regulating AMPK,which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital vaginal hypoplasia and primordial uterus caused by Müllerian anomalies. Case reports concerning adenomyosis associated with MRKH syndrome are limited, and the formation and intervention of adenomyosis without endometrium are unclear. Here, we present the case of a patient with MRKH syndrome complicated with adenomyosis without endometrium, a hypoechoic solid mass next to the right ovary. According to the intraoperative observation and histopathological examination findings, the mass were diagnosed as adenomyosis of the primordial uterus. Moreover, our report provides insights about its mechanism of occurrence and interventions in MRKH syndrome combined with adenomyosis without endometrium.