AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

The sternum is the pivotal component of the thoracic cavity. It is connected with the clavicle and ribs on the upper part and both sides respectively, and plays an important role in protecting the stability of the chest wall. Sternal resection usually results in a large segmental chest wall defect that causes the chest wall to float and requires sternal reconstruction. This paper reports a 62 years male patient with thymic squamous cell carcinoma with sternal metastasis, who underwent thymotomy, sternal tumor resection and autologous lilum graft combined with sternal reconstruction by titanium plate after relevant examination was completed and surgical contraindications were eliminated. The patient was followed up for 6 months, the respiratory and motor functions were normal and the thoracic appearance was good.

Objective: To investigate the efficacy and safety of Liqingtong (LQT) granules in patients with dampness-heat hyperuricemia. Methods: A randomized, double-blind, placebo-controlled pilot trial was conducted at the 983rd Hospital of the Joint Logistic Support Force of the People's Liberation Army from March 15, 2023, to August 10, 2023. In total, 119 participants were enrolled in this trial, and participants were given either LQT granules or placebo for 60 days based on a health education. The primary outcome was serum uric acid (SUA) level, and the secondary outcome was the traditional Chinese medicine (TCM) symptom score, measured on days 0, 30, and 60. Safety indicators, including liver function, kidney function, blood routine, glucose, blood lipid, blood pressure, and heart rate were tested on days 0 and 60 of the trial. The data were analyzed using Prism 9 software, and the significance level was set at P < .05. Results: Among 119 participants, six in the LQT granule group and seven in the placebo group dropped out, and 106 participants completed clinical observation. Baseline information, including SUA levels, TCM symptom scores, and other clinical characteristics, did not differ between the groups. At the end of the trial, compared with baseline values, the SUA levels in the LQT granule group decreased (P < .001), and no significant change was observed in the placebo group (P = .422); compared with the placebo group, the SUA levels decreased in the LQT granule group (P = .001). Compared with baseline values, the total TCM symptom scores in the LQT granule group decreased (P < .001), with no change in the placebo group (P = .136). Safety indicators did not differ significantly between the two groups. Conclusion The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.

Cirrhotic portal hypertension (CPH) is a manifestation of decompensated liver cirrhosis, with ascites, portal collateral circulation formation, hypersplenism and splenomegaly as the typical clinical symptoms. In recent years, the incidence of CPH has been increasing year by year, and the treatment of CPH has gradually become a hot issue in medical research. In order to further explore the diagnosis and treatment scheme of CPH. We briefly describe the pathophysiological mechanism and diagnosis of CPH, and the current situation of CPH treatment and the new progress of internal and external treatment were reviewed.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

BACKGROUND: Lung cancer is the cancer with the highest mortality at home and abroad at present. The detection of lung nodules is a key step to reducing the mortality of lung cancer. Artificial intelligence-assisted diagnosis system presents as the state of the art in the area of nodule detection, differentiation between benign and malignant and diagnosis of invasive subtypes, however, a validation with clinical data is necessary for further application. Therefore, the aim of this study is to evaluate the effectiveness of artificial intelligence-assisted diagnosis system in predicting the invasive subtypes of early‑stage lung adenocarcinoma appearing as pulmonary nodules. METHODS: Clinical data of 223 patients with early-stage lung adenocarcinoma appearing as pulmonary nodules admitted to the Lanzhou University Second Hospital from January 1st, 2016 to December 31th, 2021 were retrospectively analyzed, which were divided into invasive adenocarcinoma group (n=170) and non-invasive adenocarcinoma group (n=53), and the non-invasive adenocarcinoma group was subdivided into minimally invasive adenocarcinoma group (n=31) and preinvasive lesions group (n=22). The malignant probability and imaging characteristics of each group were compared to analyze their predictive ability for the invasive subtypes of early-stage lung adenocarcinoma. The concordance between qualitative diagnostic results of artificial intelligence-assisted diagnosis of the invasive subtypes of early-stage lung adenocarcinoma and postoperative pathology was then analyzed. RESULTS: In different invasive subtypes of early-stage lung adenocarcinoma, the mean CT value of pulmonary nodules (P<0.001), diameter (P<0.001), volume (P<0.001), malignant probability (P<0.001), pleural retraction sign (P<0.001), lobulation (P<0.001), spiculation (P<0.001) were significantly different. At the same time, it was also found that with the increased invasiveness of different invasive subtypes of early-stage lung adenocarcinoma, the proportion of dominant signs of each group gradually increased. On the issue of binary classification, the sensitivity, specificity, and area under the curve (AUC) values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 81.76%, 92.45% and 0.871 respectively. On the issue of three classification, the accuracy, recall rate, F1 score, and AUC values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 83.86%, 85.03%, 76.46% and 0.879 respectively. CONCLUSIONS Artificial intelligence-assisted diagnosis system could predict the invasive subtypes of early‑stage lung adenocarcinoma appearing as pulmonary nodules, and has a certain predictive value. With the optimization of algorithms and the improvement of data, it may provide guidance for individualized treatment of patients.
Adenocarcinoma/pathology* ; Adenocarcinoma of Lung/pathology* ; Artificial Intelligence ; Humans ; Lung Neoplasms/pathology* ; Multiple Pulmonary Nodules ; Neoplasm Invasiveness ; Retrospective Studies