The Hedgehog (Hh) signaling pathway is a critical transduction system regulating cell proliferation, differentiation, and tissue homeostasis during embryonic development. Its aberrant activation is closely associated with the pathogenesis of malignancies such as basal cell carcinoma and medulloblastoma. Although Smoothened (SMO)-targeting inhibitors have received clinical approval, their therapeutic efficacy is limited by acquired resistance mutation and compensatory pathway activation. Glioma-associated oncogene homolog 1 (GLI1), the terminal effector transcription factor of the Hh pathway, has emerged as a promising therapeutic target due to its tumor-specific overexpression and lower propensity for resistance induction. However, GLI1 is classified as an "undruggable" target due to the absence of well-defined ligand-binding pockets, low inhibitory activity, and poor drug-like properties. Currently, no GLI1 inhibitor has entered clinical trials. This review systematically analyzes multidimensional modulation strategies (e.g., allosteric modulation, protein-protein interaction disruption, targeted protein degradation) for targeting transcription factors, based on the structural and functional features of GLI1-DNA interaction combined with recent advances in structural biology and chemical biology, offering new paradigms to overcome therapeutic barriers against undruggable targets.

Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Objective To design an intramedullary nail that had the same ends and could be connected to hairline pointer and employ it to fixate mid-shaft clavicular fractures. Methods Sixty adult clavicles and five fresh adult cadaveric clavicles were employed to measure full length, angle between lateral and middle segments, angle between middle and medial segments as well as the narrowest outer and inner diameters of the clavicle. The interlocked intramedullary nail with the same structure of two ends was designed and used to fixate mid-shaft clavicular fractures. The nail was inserted in retrograde manner and locking screws could be inserted at beth ends. Results The full length, angle between lateral and middle segments, angle between middle and media] segments as well as the narrowest outer and inner diameters of the clavicle were (14.82 ± 1.15) cm, 30°, 30°, (1.00±0.16) cm and (0.50± 0. 18) cm respectively. After conversely placing guide pin from the fracture end, expanding medullary cavity and adjusting the nail, the designed nail was inserted into the medullary cavity from the distal or proximal ends of the clavicle, which was locked by interlocked screws. Conclusions Self-made nail takes advantages of less surgical invasion, visible fracture reduction and stable fracture fixation for treatment of mid-shaft clavicular fractures. While the biomechanieal properties of the nail need further investigation.

[Objective]To design an intramedullary nail for mid-shaft clavicular fractures based on the anatomic study of human clavicles.[Method]Sixty adult clavicles and 5 fresh cadaveric clavicles were used to survey data about full length,angle between lateral and middle segments,angle between middle and medial segments and the narrowest outer and inner diameter of clavicle.The designed interlocked intramedullary nail was used to fix mid-shaft clavicular fractures.[Result]The full length of clavicle was about(14.82?1.15) cm.The included angle between lateral and middle segment and included angle between middle and medial segment were all about 30?,the narrowest outer diameter of clavicle was about(1.00~0.16) cm,the narrowest inner diameter of clavicle was about(0.50~0.18) cm.After conversely placing guide pin from fracture end,expanding medullary cavity and adjusting the nail,the designed nail was inserted into the medullary cavity from the distal or proximal ends of clavicle,and the proximal and distal ends of the nail were locked by interlocked screws at last.[Conclusion]Treatment of mid-shaft clavicular fractures with the self-made nail has such advantages as less surgical invasion,visible fracture reduction and stable fracture fixation.The biomechanical properties of the nail will be further investigated.

OBJECTIVE:To survey and evaluate the present situation and trend of the anticancer drugs used in 6 cities of the Yangtse valley METHODS:The anticancer drugs,used in 138 hospitals of 6 cities in the Yangtse basin during the period 1999～2001,were analysed in respect to the cost,sales volume of pharmaceutical enterprises and situation of clinical application RESULTS:The costs of anticancer drugs consumption were 19 460,24 421 and 32 227 million yuan in 1999,2000 and 2001,respectively with an average annual cost of 10 238 yuan per sickbed Some new anticancer drugs derived from nature plants and monoantibodies were going to the clinical practice And gene therapy has been introduced to the treatment of cancer CONCLUSION:The anticancer drug is an important kind of drugs used in hospitals The cost per sickbed was much high and was increasing year by year Furthermore,the anticancer drugs derived from nature plants,monoantibody and the gene therapy will be the predominant measures in the future

OBJECTIVE:To analyze the present situation and trend of the application of antituberculotics in hospitals of 6 cities METHODS:The antituberculotics used in 138 hospitals of 6 cities during the 1999～2001 period were analysed in respect to the cost,sales volume of pharmaceutical enterprises and situation of clinical application RESULTS:The costs of consumption of antituberculotics were 6 227 520,7 204 738 and 7 537 601 yuan in 1999,2000 and 2001 respectively with a rising trend year by year The average annual cost of antituberculotics was 282 yuan per sickbed CONCLUSION:The antituberculotics are fewer in kind and inexpensive in price but they occupy an important place in a hospital and their consumption is unceasingly increasing

OBJECTIVE:To survey and evaluate the present situation and trends of antidiabetic drugs used in18hospitals of Chongqing during the period2000～2002.METHODS:Data of antidiabetic agents used in18hospitals of Chongqing were collected and analysed concerning the consumptive sum and main kinds.RESULTS:The consumption sums of antidiabetic a?gents in the years2000,2001and2002were498,643and649tenthousand yuans(RMB),respectively,with an annual increase rate of15.03%.The cost for insulin injections accounted for38.56%of the total consumption sum of antidiabetic agents,and that for mixed insulin took59.02%of the consumption sum for insulin.CONCLUSION:Antidiabetic agent was an important kind of drug with developing potential.The consumption of mixed insulin injection and new kind of oral antidiabetic agents is increasing fast year by year.

Objective To improve the diagnostic rate of laparoscopy for malignant peritoneal mesothelioma (MPM) and enhance acquaintance with this disease. Methods The appearance of laparoscopic detection was retrospectively analysed in 25 patients with pathologically proved MPM. Results Hyperemia, edema and faint vascular net in parietal peritoneum were seen in all patients, and the thick or thin callus-like thickened parietal peritoneum was also observed. There were some grey nodes of various size, distribution and number in parietal and visceral peritoneum in all patients. The purplish red masses with hyperemia and edema were seen in abdominal cavity in 21 patients (21/25,84%). Several small masses cold be connected each other to become one big mass. All patients had yellow turbid or bloody ascites. Conclusion MPM had special characteristics under laparoscopy. Laparoscopic detection possesses the advantages of safety, little trauma, less hurt and high diagnostic rate. Laparoscopic detection and biopsy may be the best method for diagnosis of MPM.