Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

OBJECTIVE: To explore the methods, fixation points, and effectiveness of staged therapy using external fixation frame in treatment of infectious nonunion near knee joint. METHODS: A retrospective analysis was conducted on the clinical data of 60 patients with infectious nonunion near knee joint, who underwent staged therapy using external fixation frame between June 2021 and June 2024 and were followed up. There were 48 males and 12 females with an average age of 47.9 years (range, 16-70 years). The disease duration ranged from 9 months to 20 years, with a median of 14 months. Among them, 21 cases of infectious nonunion located in the distal femur, 36 cases in the proximal tibia, and 3 cases in the patella; 12 cases exhibited segmental bone defects (≥4 cm), while 48 cases presented with localized bone defects (<4 cm). Osteomyelitis was classified using the Cierny-Mader system, with 3 cases classified as type Ⅰ, 6 cases as type Ⅱ, 35 cases as type Ⅲ, and 16 cases as type Ⅳ. Preoperative C-reactive protein levels ranged from 15.1 to 55.8 mg/L (mean, 36.4 mg/L). The erythrocyte sedimentation rate was 35-80 mm/1 h (mean, 56.9 mm/1 h). The Hospital for Special Surgery (HSS) score for knee joint was 69.3±17.7 and the range of motion was (70.61±40.60)°. After debridement and placement of antibiotic carriers at the first-stage operation, unilateral orbital frames ( n=14), combined frames ( n=27), or Ilizarov frames ( n=19) were used for cross joint fixation ( n=9) or joint preservation fixation ( n=51). After 6-8 weeks of infection control, the bone grafting or bone transport was performed at the second-stage operation based on the type of bone defect, with internal fixation employed as an adjunct if necessary. After operation, the infection control and fracture healing were observed and the bone healing time was recorded. The knee joint function was assessed using the HSS score, and the knee joint range of motion was measured as well as the angle of motion loss. Patients were grouped according to the site of nonunion, type of external fixation frame, and fixation method. The bone healing time, change value of HSS score, and knee joint range of motion loss (difference between pre- and post-operation) were compared between groups. RESULTS: All infection markers returned to the normal range within 6 weeks after the first-stage operation. All patients were followed up 12-48 months (mean, 22.0 months) after the second-stage operation. There were 5 cases of needle tract infection during the external fixation period, and 3 cases of infection recurrence after the second-stage operation, all of which were cured after symptomatic treatment. The bone healing time was 6-18 months (mean, 11.0 months). At last follow-up, the HSS score was 88.5±7.9 and the range of motion was (61.84±40.59)°, with significant differences compared to preoperative values ( P<0.05); the knee joint range of motion loss was (8.77±11.07)°. The bone healing time was significantly longer in the distal femur group than in the proximal tibia group ( P<0.05), and in the unilateral orbital frames group than in the Ilizarov frames group and the combined frames group ( P<0.05). The angle of motion loss was significantly larger in the Ilizarov frames group than in the unilateral orbital frames group and the combined frames group ( P<0.05). The change value of HSS score was significantly higher in the cross joint fixation group than in the joint preservation fixation group ( P<0.05). CONCLUSION During the first-stage operation, debridement is performed and antibiotic carriers are placed to control infection. External fixation frames are then precisely positioned based on the distance between the lesion and the joint surface, avoiding the infected wound while ensuring mechanical balance. During the second-stage operation, bone grafting options are selected according to the extent of bone defects to enhance the bone union. Postoperative early functional exercises of the knee joint are permitted to improve joint function.
Humans ; Male ; Female ; Middle Aged ; Adult ; Fractures, Ununited/surgery* ; Retrospective Studies ; External Fixators ; Aged ; Knee Joint/surgery* ; Adolescent ; Young Adult ; Treatment Outcome ; Osteomyelitis/surgery* ; Fracture Fixation/instrumentation* ; Bone Transplantation ; Tibial Fractures/surgery*

OBJECTIVE: To explore the effectiveness of primary interventional revascularization combined with secondary perforator composite flap in the treatment of peripheral arterial disease (PAD) accompanied by soft tissue defects around the ankle. METHODS: Between January 2022 and January 2025, 12 patients with PAD and soft tissue defects around the ankle were admitted. Among them, there were 9 males and 3 females; their ages ranged from 52 to 82 years, with an average of 68.9 years. The causes of injury included 4 cases of traffic accident, 5 cases of falls, 1 case of falling from height, 1 case of foreign body puncture injury, and 1 case of electric shock injury. The infection duration ranged from 1 month to 35 years, with a median duration of 3.5 months. The wound size ranged from 5.5 cm×3.0 cm to 15.0 cm×9.0 cm. The ankle-brachial index (ABI) was 0.32±0.12. The visual analogue scale (VAS) score for pain was 3.3±0.5. Preoperative vascular stenosis assessment was performed in all patients, with primary intervention to dredge large and medium-sized arteries, followed by secondary repair of the wound using a perforator composite flap. The flap size ranged from 6.5 cm×4.0 cm to 16.0 cm×10.0 cm. The donor sites were sutured directly or repaired with skin grafts. After two stages of treatment, the effectiveness was evaluated by measuring ABI, observing flap survival and wound healing, assessing VAS scores, and American Orthopedic Foot and Ankle Society (AOFAS) scores. RESULTS: All 12 cases completed two stages of treatment; all patients were followed up after the second-stage treatment, with a follow-up period ranging from 7 to 28 months, with an average of 16.8 months. After the first-stage treatment, the skin temperature around the ankle was significantly higher than that before treatment, and the ABI increased to 0.71±0.07, with a significant difference ( t=9.918, P<0.001). After the second-stage treatment, the blisters on the distal end of the skin flap occurred in 3 cases. The flaps survived and the wounds healed, with a healing time ranging from 10 to 14 days (mean, 11.8 days). The incisions at the donor site healed by first intention, and the skin grafts survived. The VAS score was 0.5±0.5 at 3 weeks, which was significantly lower than that before treatment ( t=13.675, P<0.001). No infection recurrence occurred during follow-up. At 6 months after the second-stage treatment, the AOFAS score of the ankle joint ranged from 92 to 97, with an average of 94.7, all reaching excellent. CONCLUSION Interventional revascularization combined with perforator composite flap for staged treatment of PAD with ankle soft tissue defects can obtain good effectiveness, by unclogging the main blood vessels, improving lower limb blood supply, and improving the survival rate of the skin flap.
Humans ; Male ; Female ; Middle Aged ; Aged ; Peripheral Arterial Disease/surgery* ; Soft Tissue Injuries/surgery* ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Aged, 80 and over ; Ankle/blood supply* ; Treatment Outcome ; Ankle Brachial Index ; Skin Transplantation/methods*

Membrane protein degradation is a cutting-edge field in targeted protein degradation (TPD). Herein, we developed glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) as a novel strategy for the targeted degradation of tumor-specific membrane proteins. GLTACs utilize tumor-specific expression and endocytosis properties of GPC3 to degrade membrane proteins. By conjugating a GPC3-targeting peptide with the ligand of protein of interest (POI), GLTACs induce the formation of a ternary complex that is internalized into lysosomes, leading to the degradation of the POI. The effectiveness and specificity of GLTACs were validated by designing PD-L1, c-Met, and FGFR1 degraders. In particular, GLTAC WP0 potently degraded PD-L1 and induced T-cell-mediated tumor killing against HepG2 cells, highlighting the potential therapeutic applications. The development of GLTAC technology expands the scope of TPD strategies and opens new avenues for discovering novel therapeutic modalities against challenging protein targets.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Using methylated pyrroloxicam as a starting material and following the principles of drug design such as bioisosterism and active site binding,we designed and synthesized ten structurally novel target compounds,whose structures were characterized by 1H NMR and MS analysis.The in vitro antitumor activity of these title compounds was evaluated by measuring their inhibitory activity against pancreatic cancer cells Capan-1,leukemia cells L1210,and human liver cancer cells SMMC-7721.The results showed that compound 6f(IC50=4.8±0.5 μmol/L)exhibited good inhibitory activity against Capan-1 pancreatic cancer cells,that compound 6b(IC50=2.6±0.3 μmol/L)showed good inhibitory activity against L1210 leukemia cells,and that compound 6c(IC50=2.1±0.2 μmol/L)displayed good inhibitory activity against SMMC-7721 human liver cancer cells.These preliminary results from the antitumor activity experiments suggest that the introduction of benzothiazine derivatives plays a certain role in enhancing the antitumor activity of this class of compounds.

Objective:To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments).Methods:A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed.Results:Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment ( P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments ( P＜0.001). Conclusions:Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

Objective:To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments).Methods:A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed.Results:Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment ( P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments ( P＜0.001). Conclusions:Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.

Objective:To characterize the complete genome sequence and elucidate the structural features of norovirus (NoV) isolate SD20200267.Methods:The viral nucleic acid was extracted from patient samples, followed by amplification and sequencing for genotyping based on the nucleotide sequences. The metagenomic sequencing technology was utilized for whole genome sequencing, and subsequent analysis was performed on the acquired nucleotide sequences.Results:The complete genome sequence of the SD20200267 strain, spanning a total length of 7 465 nucleotides, was successfully obtained. The SD20200267 strain belongs to the GⅡ.12 and GⅡ.P16 genotypes in the VP1 and RdRp regions, respectively. The nucleotide sequence identity of SD20200267 strain with other GⅡ.12[P16] strains ranged from 96.0% to 97.3%, exhibiting 15 amino acid variations. The strain displayed evidence of recombination, with the recombination site located in the overlapping region of ORF1 and ORF2.Conclusions:SD20200267 is classified as a GⅡ.12[P16] strain, and recombination was observed in the overlapping region of ORF1 and ORF2.