Pan-cancer analysis of heterogeneity of tumor mutational burden and genomic mutation under treatment pressure.

BACKGROUND: High tumor mutational burden (TMB) is one of the widely researched predictive biomarkers of immune checkpoint inhibitors and has been shown to be closely related with response to immunotherapy in multiple cancer types. However, for patients who have failed conventional therapy and are about to undergo immunotherapy, there is no consensus recommendation on the timing of tumor sampling for TMB analysis, and the effects of different therapies on TMB have not been clarified. This retrospective observational study aimed to investigate the heterogeneity of TMB and genomic mutation under the treatment pressure. PATIENTS AND METHODS: We retrospectively collected the available genomic and therapeutic information from 8051 samples across 15 tumor types (>50 samples/tumor) found in 30 published studies and investigated the distribution and heterogeneity of TMB under treatment across diverse cohorts. RESULTS: This integrated analysis has shown anticancer treatments increased TMB. Significant effects of treatment on TMB were more frequently observed in tumor types with lower treatment-naïve TMB, including breast, prostate, and pediatric cancers. For different cancer therapies, chemotherapy was prone to be correlated with an increased TMB in most cancer types. Meanwhile, the fraction of the TMB-high category of breast, prostate, and bladder cancers and glioma increased significantly after chemotherapy. Several actionable genes including ERS1 and NF1 in breast cancer, as well as some prognostic markers including TERT in bladder cancer and IDH1 in glioma, were significantly changed in post-chemotherapy tumors compared to treatment-naïve tumors. CONCLUSION: Our study reveals the heterogeneity of TMB under treatment across diverse cancer types and provides evidences that chemotherapy was associated with increases in TMB as well as the fraction of TMB-high category, suggesting that resampling tumor tissues for calculating post-chemotherapy TMB could be a better option for predicting the response to immunotherapy, especially for tumors with initially low TMB.

[A case of Stevens-Johnson syndrome with binocular corneal perforation and multiple corneal transplantation which was difficult to control].

The 31-year-old female patient was admitted to the General Hospital of the Chinese People's Liberation Army for 3 days after the corneal transplantation of her right eye for 5 months.Four years ago, the patient developed red eyes, pain, dryness and photophobia after intravenous drip of cefuroxime sodium and metronidazole due to pelvic inflammation, accompanied by high fever, systemic rash and epidermal exfoliation, fingernail peeling, and mucosal ulceration in the eyes and mouth.Later, the patient received systemic hormone shock and point eye treatment in a local hospital, and the dry eyes gradually worsened. Despite continuous artificial tears and bandage mirror treatment, the corneal ulcer perforation in both eyes still occurred successively. After several penetrating keratografts and drug therapy, the ulcer and dissolution could not be prevented. He was admitted to our hospital due to corneal perforation in both eyes.Ophthalmic examination: visual acuity manual/15 cm in the right eye, intraocular pressure T-2, conjunctival sac stenosis, extensive corneal opacity and edema, ulcer about 8 mm, corneal perforation near the corneal limbus about 2 mm×5 mm below.The left eye had no light perception, a central corneal ulcer of about 8 mm, bulge of the posterior elastic layer, no anterior chamber, and atrophy of the eyeball.B-ultrasound showed choroidal detachment of the right eye.On the second day, the patient received right eye intraocular exploration, vitrectomy, ecotopic keratoscleral carrier Boston Ⅱ artificial keratoplasty, glaucoma valve implantation, autogenous ear cartilage implantation, conjunctival occlusion, and left eye lamellar keratoplasty, conjunctival occlusion.Postoperative visual acuity of right eye was -6.50 DS=0.12, intraocular pressure TN, ocular surface was stable.The left eye has no light perception and the ocular surface is stable.

[Progress in the diagnosis and treatment of oropharyngeal cancer].

SummaryIn recent years，human papillomavirus has been proved to be closely related to the occurrence and prognosis of oropharyngeal cancer.The treatment of oropharyngeal cancer has evolved from the primary radiotherapy to the corresponding treatment according to different tumor stages.For patients with advanced oropharyngeal cancer，the treatment strategy is mostly surgery + postoperative concurrent chemoradiotherapy.Patients are often accompanied by large defects in the surgical area after surgery.With the improvement of head and neck surgical repair technology and the progress of free flap technology，various repair methods can be adopted to repair and reconstruct.

Experimental investigation on dynamic characteristics and strengthening mechanism of laser-induced cavitation bubbles.

The dynamic features of nanosecond laser-induced cavitation bubbles near the light alloy boundary were investigated with the high-speed photography. The shock-waves and the dynamic characteristics of the cavitation bubbles generated by the laser were detected using the hydrophone. The dynamic features and strengthening mechanism of cavitation bubbles were studied. The strengthening mechanisms of cavitation bubble were discussed when the relative distance parameter γ was within the range of 0.5-2.5. It showed that the strengthening mechanisms caused by liquid jet or shock-waves depended on γ much. The research results provided a new strengthening method based on laser-induced cavitation shotless peening (CSP).

[Effects of dingduwan on electric activities of gastrointestinal smooth muscle and effect of gastrointestinal motility].

Dingduwan (DDW) is a Chinese herbal medicine. Method of modified synchronous recording was used to study the electric activities of gastrointestinal (GI) smooth muscle and the effect of GI motility treated by DDW. A dosage of 3.5 g/kg for ingestion in rats markedly increased the average amplitude of GI slow wave, the total amplitude of GI motion, the rate of GI slow wave and intestinal motion (P < 0.05), but it had no significant effects on the frequency of gastroelectric slow wave and gastric motility (P < 0.05). DDW in the dosage of 5.2 g/kg for ingestion markedly promoted the recovery of intestinal intussusception in mice (P > 0.05). The results showed that DDW markedly increased the intestinal electricity and motility more than that of stomach.

[Studies on the alkaloids of Gynura segetum (Lour.) Merr].

Six alkaloids were isolated from Gynura segetum (Lour.) Merr. Four of them were identified. Alkaloids I and II were identified as known senecionine and seneciphylline, respectively. Alkaloids III and IV were found to be new compounds named seneciphyllinine and (E)-seneciphylline respectively. Their structures were confirmed on the basis of spectral data (UV, IR, MS, 1HNMR, 13CNMR, C-H COSY).